From owner-ageing@net.bio.net Mon Apr 01 23:00:00 1996 Path: biosci!INFAR.EPM.BR!SSMAILI.FARM From: SSMAILI.FARM@INFAR.EPM.BR ("Soraya Smaili") Newsgroups: bionet.molbio.ageing Subject: unsubscribe Date: 2 Apr 1996 06:36:59 -0800 Organization: infar Lines: 5 Sender: daemon@net.bio.net Distribution: world Message-ID: <19B312B43D8@infar.epm.br> NNTP-Posting-Host: net.bio.net Unsubscribe, Thank you. From owner-ageing@net.bio.net Mon Apr 01 23:00:00 1996 Path: biosci!ns1.faseb.org!lamarck.sura.net!ra.nrl.navy.mil!news.math.psu.edu!chi-news.cic.net!newsxfer2.itd.umich.edu!gatech!psinntp!psinntp!psinntp!psinntp!usenet From: yo_doc@usa.pipeline.com(Richard A. Lockshin) Newsgroups: bionet.molbio.ageing, Subject: NYC AREA CELL DEATH CLUB MEETING, ADDRESSES Date: 2 Apr 1996 19:22:23 GMT Organization: Pipeline USA Lines: 48 Message-ID: <4jrupf$h16@news1.h1.usa.pipeline.com> NNTP-Posting-Host: 38.8.149.7 X-PipeUser: yo_doc X-PipeHub: usa.pipeline.com X-PipeGCOS: (Richard A. Lockshin) X-Newsreader: Pipeline USA v3.4.0 NYC Area Cell Death Club Next meeting: Wednesday, April 10, 1996 6:00-6:30 PM Pizza 6:30-8:00 PM Talks and discussion Rockefeller University, 1230 York Ave., Weiss Research Bldg Room 301 Free Parking after 5PM at 66th St. & York Ave (Please carpool as parking space is limited) Speakers: 1. Dr. Ralph Buttyan, Dept. of Urology, Columbia University APOPTOSIS IN PROSTATE CANCER 2. Dr. Carol Troy, Dept. of Pathology, Columbia University MECHANISMS OF NEURONAL CELL DEATH. A FINAL COMMON PATHWAY? To help plan for pizza call lab of Dr. Zahra Zakeri, 718: 997-3429 and let them know the number coming for pizza, talk, and if you need parking. Please RSVP by Tues, March 5, 1996. Otherwise email to me here or to lockshin@sjumusic.stjohns.edu IF YOU WANT TO RECEIVE DIRECT EMAIL NOTIFICATION, PLEASE SEND REPLY, FILLING IN THE FOLLOWING BLANKS (NO SPACES AFTER COLON) FIRST NAME: LAST NAME: EMAIL ADDRESS: ADDRESSLINE1: ADDRESSLINE2: INSTITUTION: STREETADDRESS: CITY: STATE: ZIP: INTEREST: Organizers: Zahra Zakeri, Fax 718: 997-3445 Phone 718: 997-3417 Raymond Birge: Fax 212 327-7943; Phone 212: 327-7412 Richard Lockshin Fax 718: 990-1854 Phone 718: 380-8543 Sponsored by: Oncor Appligene Cell Death and Differentiation -- Richard A. Lockshin -- Richard A. Lockshin From owner-ageing@net.bio.net Mon Apr 01 23:00:00 1996 Path: biosci!CS.Arizona.EDU!news.Arizona.EDU!hamblin.math.byu.edu!acs2.byu.edu!news.cuny.edu!news.sprintlink.net!new-news.sprintlink.net!newsreader.sprintlink.net!imci3!imci4!newsfeed.internetmci.com!swrinde!howland.reston.ans.net!torn!newshost.uwo.ca!usenet From: Charles Carter Newsgroups: bionet.molbio.ageing Subject: Re: Telomerase Trouble Date: 2 Apr 1996 15:16:50 GMT Organization: The University of Western Ontario, London, Ont. Canada Lines: 29 Message-ID: <4jrgd2$t9e@falcon.ccs.uwo.ca> References: <315DE2DF.520F@novell2.bham.ac.uk> NNTP-Posting-Host: ts10-2.slip.uwo.ca Mime-Version: 1.0 Content-Type: text/plain; charset=us-ascii Content-Transfer-Encoding: 7bit X-Authenticated: pts1010@ts10-2.slip.uwo.ca X-Mailer: Mozilla 1.22 (Windows; I; 16bit) imm3gjg7@NOVELL2.BHAM.AC.UK ("G.J.Griffiths") wrote: >So if it's true that the telomere length dictates cellular ageing, then >what would be the easiest way to maintain it in cells? How would it >posible to upregulate telomerase expression? Three methods spring to >mind. Before we get ahead of ourselves and look for a way to incorporate the telomerase enzyme (or more simply the telomerase gene via a retrovirus of some sort) into all of the cells of a fully developed multicellular organisms, shouldn't we apply gene therapy to an embryonic mouse cell and see how long it lives? Or maybe we should make antibodies to telomerase or use antisence regulation (cDNA's of the telomerase mRNA) to inhibit its translation and see if we can make senesence come sooner. By the time we prove that telomerase is behind aging, there may be better gene targeting methods at our disposal that can be used to change all of our own cells, and not just those of our unborn children. Or maybe you do an experiment with nematodes (ie, C. elegans) where you look for a correlation between telomerase efficiency and lifespan? Make a few (~10) isolated communities of varying lifespans and sample some of each (throw them in a blender or polytron) and check out their mRNA or telomerase functioning with some sort of assay. After you gather the lifespan data for each community you can do some regressions and so forth. Anyways, I'm just thinking out loud.. Chuck From owner-ageing@net.bio.net Mon Apr 01 23:00:00 1996 Path: biosci!ns1.faseb.org!lamarck.sura.net!ra.nrl.navy.mil!news.math.psu.edu!psuvax1!news.ecn.bgu.edu!vixen.cso.uiuc.edu!newsfeed.internetmci.com!howland.reston.ans.net!torn!newshost.uwo.ca!usenet From: Charles Carter Newsgroups: bionet.molbio.ageing Subject: Re: Life extension in rats. Date: 2 Apr 1996 15:22:01 GMT Organization: The University of Western Ontario, London, Ont. Canada Lines: 13 Message-ID: <4jrgmp$t9e@falcon.ccs.uwo.ca> References: <4jovk8$61m@mother.usf.edu> NNTP-Posting-Host: ts10-2.slip.uwo.ca Mime-Version: 1.0 Content-Type: text/plain; charset=us-ascii Content-Transfer-Encoding: 7bit X-Authenticated: pts1010@ts10-2.slip.uwo.ca X-Mailer: Mozilla 1.22 (Windows; I; 16bit) mmunoz1@chuma.cas.usf.edu (Mauricio Munoz (BIO)) wrote: >I would like to share a new observation that was made here at the >University of South Florida. It has been found that with the addition of >an antioxidant (PBN) and minimal addition of vitamim B and A, laboratory >rats have had a 10% life extension in a period of about two months. The >rats were also found to have an increase in intelligence. What was used as a control? Chuck From owner-ageing@net.bio.net Tue Apr 02 23:00:00 1996 Path: biosci!ihnp4.ucsd.edu!news1.ucsd.edu!usenet From: Oliver Bogler Newsgroups: bionet.molbio.ageing Subject: Re: Premature Ageing Date: Tue, 02 Apr 1996 17:10:36 -0700 Organization: The University of California at San Diego Lines: 169 Message-ID: <3161C1FC.4F26@ucsd.edu> References: <4i13j9$go6@bisance.citi2.fr> <4jgjp5$2u9@sydney1.world.net> NNTP-Posting-Host: licr-user003.ucsd.edu Mime-Version: 1.0 Content-Type: text/plain; charset=us-ascii Content-Transfer-Encoding: 7bit X-Mailer: Mozilla 2.01 (Macintosh; I; 68K) Guy Dunphy wrote: > > Oliver Bogler wrote: > > >Guy Dunphy wrote: > > >> Anyone know if more recent work has examined the condition of the telomeres > >> in Werner syndrome patients? > > Well? I didn't answer because I don't know. > >> Isn't it amazing the number of researchers who are looking into telomeres, > >> 'just for the cancer connection'! > >> What a bunch of funding whimps. Go on, admit it you guys, WE ALL WANT TO BE > >> IMMORTAL. (snip) > >This is all very interesting, but you seem to unaware that there is no evidence of a > >connection between telomere length/cellular ageing and organismal ageing. Organismal > >ageing is better discussed in terms of mortality - no one dies of "old age". > > Oddly enough, that was what my grandfather died of. > > >There is always a "pathology", and that has nothing to do with telomere length. > > Now who' s making unproven assertions? OK - so why don't you define the condition that immeadiately precedes death by old age. Please remember that kidney failure, pneumonia or other opportunistic infections permitted by a failing immune system, strokes, heart attacks etc. are all defined pathologies that are different from old age. I suggest that those deaths that are attributed to old age are just not carefully defined in other terms. The underlying point is that telomere shortening does not lead to an inevitable death or pathology. People with very short telomeres, and fibroblast clones that can only undergo very few divisions, can still live for many years (eg. George Burns). In contrast other people with longer telomeres, and more vibrant fibroblast clones, can die of pathologies otherwise associated with old age (Sergei Gringkov, about 30 year old Russian gold medalist in pairs skating who died of heart disease at the end of last year). > >Of course, older > >people have older cells that may be less good at doing their stuff, contributing to a > >conditions that kills. > > Exactly. Even where infectious disease was the cause of death, perhaps an > immune system with a smaller proportion of 'tellomere challenged' cells would > have mounted an effective defense. So how do we ever decide whether the root > cause of a particular death was short tellomeres. Can't. All we can do is see if > an experimental population with 'new, improved' tellomere restoration has longer > average lifetimes than a control. So far a pretty good correlation between cancer and telomerase activity has been established. Those who believe that telomeres are key to cell ageing and on the other side of the coin cancer, would surely argue that your experiments would lead to increased cancer risk. No evidence that telomere length determines the effectiveness of a cell, say of the immune system, exists > >Also, the fossil record would look at people with no basic health care or sanitation, that > >were predated actively. Hardly a fair comparison. > > My point was, that all other things (predation, lifestyle, etc) remaining equal, > there may have been a relatively sudden change in average human lifespan. > I wondered if any one could examine a human bone fossil and say: "Hey, this > fellow was 200 years old when he died!" How would we tell? > Are there no instances of other species, where there are two distinct strains, > differing only in their average lifespans? Which strain would win out in an > evolutionary contest? You can tell alot from the bones - for example the wear and tear on teeth. And you might say that the longests telomere lengths in the worls won't help you survive if you don't have teeth to eat with (I'm talking in the stone age etc). > >In general, in the wild, animals never > >reach their maximum possible age because they get eaten first! > > Probably true, animals always get eaten before 'maximum' age. But humans > (even prehistoric ones) have social structures that tend to distort such purely > ecological models. I would include diseases in the environmental effects that lead to death before ageing can affect the organism in pre modern medical society. Therefore, modern sanitation followed by antibiotics are the two advances that significantly affected mortality. These advances are purely cultural, and so independant of biological evolution. They have, if you will, unmasked ageing and new age-related diseases such as heart attacks and cancer. > >So I guess, most scientists who work on telomeres do so to learn more about tumors, than > >for the sake of living forever. Also the connection between cellular ageing and telomere > >length is so far only correlative: no direct evidence of causation has been provided. > > And the way to prove it, is to switch on the teleomere patch-up system in a cell > line, and see what happens. You know that, right? Anyone trying to do it? The problem is that telomerase, the enzyme that extends telomeres, is a multicomponent complex, and until all the components are cloned, there is no way to do the experiment. Experiments have shown that the amount of the one part (the RNA component) that is cloned is not a good indicator of telomerase activity. snip. > Certainly, I'm aware there is no direct proven link yet. But then, I'm not > writing research papers, I'm just speculating. So I don't have to stick to > discussion of proven facts. That is your perogative. Of course, it will detract somewhat from the discussion, and temper the enthusiasm of those responding to your posts. snip > And in this case, my speculation is that as the telomeres shorten (at differing > rates) in the various populations of cells in the body, and the statistical > spread (of cells in each line that have exhausted their telomeres and begun to > suffer loss of whatever genes were nearest the fraying ends The "genes at the ends of chromosomes" theory is clearly wrong - they have simply no tbeen found. More likely, is that the frayed end of a chromosome signals the cell cycle machinery of the cell (which regulates cell division) to halt the process until the damaged DNA can be repaired. This is a fairly well established mechanism in other situations (eg chromosome breaks). snip > After all, there are _lots_ of variables. Telomere exhaustion will doubtless > occur at different rates in different:- > - individuals (hence the spread of rates of aging between people) I feel compelled to repeat that there is no established link between telomere length and life expectancy. Telomeres are not the holy grail of ageing research. Many cells in the body are post-mitotic - they never divide after development is complete. They can live for very long times with no reference to their telomeres, without telomerase activity and lengthening their telomeres would have no effect. By weak analogy, the telomere might be more like the tire on a car. If you want to drive somewhere, you need the tire. If you're parked for good, you don't need it. The tire does not actually move the car, though you might be initally mislead into thinking it does - after all that's where the car and the road meet. > - cell lines (so different organs and metabolic systems will 'age' > differently in any individual) > - individual chromosomes (and hence 'hit' different genes first - so the > mechanisms of failure will be many and varied.) > In a given individual, with so many different modes of failure coming into play, > all of them in statistical fashion among cell populations (rather than all or > nothing effects), then its no wonder that aging looks like a general systemic > decline in effectiveness. Does it? > Then again, I'd be surprised if other age related problems (such as mechanical > and structural wear and alteration) don't show up in the first experimental > subjects to have their 'telomere aging' fixed. > For instance, there's also the mitochondria functionality problem. > > But I just have a gut feeling that telomere loss is the major cause of the > 'cellular death' clock. (Hope its not just wishful thinking.) There is no cellular death clock - you may be thinking of cellular senescence. Senescent cells are not dead - they accumulate with age, but can be viable for many years as old people show. > Incidentally, while I'm talking to someone who no doubt knows, are there > any listservers that carry more detailed information about this topic? Sorry - I don't know. Thank you for an interesting discussion. Best wishes, Oliver From owner-ageing@net.bio.net Tue Apr 02 23:00:00 1996 Newsgroups: bionet.molbio.ageing Path: biosci!daresbury!sunsite.doc.ic.ac.uk!lyra.csx.cam.ac.uk!uknet!uknet!psinntp!psinntp!psinntp!pfizergate!news From: "Mark R. Miglarese" Subject: Re: Telomerase Trouble X-Nntp-Posting-Host: miglaresemr.pfizer.com Content-Type: text/plain; charset=us-ascii Message-ID: To: imm3gjg7@NOVELL2.BHAM.AC.UK Sender: news@pfizer.com (News Admin) Content-Transfer-Encoding: 7bit Organization: Pfizer Inc References: <315DE2DF.520F@novell2.bham.ac.uk> Mime-Version: 1.0 Date: Wed, 3 Apr 1996 17:09:52 GMT X-Mailer: Mozilla 1.1 (Macintosh; U; PPC) X-Url: news:315DE2DF.520F@novell2.bham.ac.uk Lines: 27 Points to consider: 1. Human telomerase has not been cloned or purified yet. It is a huge ribonucleoprotein complex (>800 kDa) which is very difficult to work with. 2. All issues concerning gene therapy apply (delivery etc.). 3. Most importantly, increased telomerase activity is associated with a wide variety of tumors. In short, cells that live longer are more likely to become transformed. In fact, telomerase is being actively targeted by several labs in the hope of inhibiting tumor growth. Upregulating it in normal cells would not be a good idea. Mark R. Miglarese, Ph.D. Cancer Research Pfizer Central Research Box 372 Eastern Point Road Groton, CT USA 06340 Phone: (860) 441-8478 FAX: (860) 441-1290 Email: miglaresemr@pfizer.com From owner-ageing@net.bio.net Tue Apr 02 23:00:00 1996 Path: biosci!rutgers!news.iag.net!news.math.psu.edu!psuvax1!uwm.edu!cs.utexas.edu!usc!howland.reston.ans.net!surfnet.nl!swsbe6.switch.ch!scsing.switch.ch!news.rccn.net!master.di.fc.ul.pt!skull.cc.fc.ul.pt!qjpcbraz From: Jorge Braz Newsgroups: bionet.molbio.ageing Subject: DNA base damage by oxygen radicals Date: Wed, 3 Apr 1996 11:54:28 +0200 Organization: Faculdade de Ciencias da Universidade de Lisboa Lines: 9 Message-ID: NNTP-Posting-Host: skull.cc.fc.ul.pt Mime-Version: 1.0 Content-Type: TEXT/PLAIN; charset=US-ASCII Hi there Can you tell me anything about base damage in cytosine by oxygen species. I'm doing a theorical work and I would like to know mechanisms and kinetic or thermodinamic constants for the degradation of cytosine. Thanks in advance Jorge Braz From owner-ageing@net.bio.net Tue Apr 02 23:00:00 1996 Path: biosci!internet!biosci!not-for-mail From: biohelp (BIOSCI Administrator) Newsgroups: bionet.molbio.ageing Subject: IMPORTANT - BIOSCI Fundraising Update! Date: 3 Apr 1996 02:01:30 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 149 Sender: daemon@net.bio.net Distribution: world Message-ID: <199604031000.CAA13609@net.bio.net> NNTP-Posting-Host: net.bio.net I'm interrupting the usual monthly posting of the BIOSCI miniFAQ to bring you up to date on BIOSCI fundraising progress, a topic of concern to your future use of this resource. Thank you in advance for taking the time to read this message carefully. Last year we announced that BIOSCI was going to adopt the U.S. Public Broadcasting System model to fund its operations after our DOE/NSF grant runs out later this year. Unlike PBS, we are not soliciting contributions from users; we are only selling ads on our Web pages solely to cover our operating costs. Our goal is to seek sponsorships until we build up an operating reserve of about $100,000 and then cease further promotions until we need to build the reserve back up. (The accountants among our readership will be familiar with the problem of deferred revenue which we can not safely utilize until ads have been displayed for a period of time.) We have three sponsors to date with a couple more pending. The process is time-consuming, however, and we need your help as explained further below. Our operating costs consist of our network connection, phone lines, hardware maintenance (we hope to have new and faster hardware soon!), plus 0.7 FTE of salaries covering UNIX systems admin, technical support, quality assurance, i.e., testing, of our system, and administrative costs (such as the time it takes to actually find/write/call potential sponsors and raise money!). Although the BIOSCI staff does get compensated for a portion of the work that they do, this project has always received a lot of free after-hours and "vacation" time labor, so we hope that no one will begrudge the time that we do charge to the project to serve you. All of the three part-time staff members, Dave Mack, Julie Lawrence, and myself, have full time day jobs and families in addition to working hard to keep this service running for all of you. Julie and Dave Mack are subcontractors for BIOSCI; my time that is charged to the project defrays a portion of my regular salary instead of adding to my income. Besides having to relocate the project, we were very busy this last year building new infrastructure such as our WWW hypermail interface to the system. This was released last December along with scores of WAIS indices for the newsgroups. Virtually everything is complete, although we do continue to find and fix bugs (many through your helpful feedback!). We are still having some problems with our WAIS indexing. The archives continue to grow rapidly. We are running over 100 indexes now versus three previously and any systems crashes cause greater havoc with the indexing than before! We are still working to fix this as fast as our resources permit and appreciate your patience, but we have been able to automate a lot of the infrastructure to reduce labor as compared to past requirements. We have also implemented new software to make moderation of BIOSCI/bionet newsgroups much easier and combat the growing problem of Internet junk mail and USENET "spamming." About 20% of our groups are now moderated, many of them by the BIOSCI staff! This, for example, made a major difference last year in the quality of content in our EMPLOYMENT/bionet.jobs.offered newsgroup which many commercial concerns and recruiting firms are using **without charge** to recruit candidates for positions in the biological sciences. We are also now in a position to have sponsors for individual newsgroups as you will have noticed if you have visited http://www.bio.net/ and clicked on "Access the BIOSCI/bionet newsgroups" recently. So, how can you help?? ---------------------- As noted above it can take a lot of time to contact potential sponsors if I have to do it all myself. Our request is quite simple. You can do two important things which will take very little time for you individually. First, please use our WWW system at http://www.bio.net/ to access the archives. You can now post or reply to messages via your Web browser. Your usage helps attract sponsors. If you contact any of our sponsors, please be sure to thank them for supporting BIOSCI. It is critical for them to get this feedback if they are to continue their sponsorship for the long term. Second, if you work for a company or organization that provides products or services of interest to the biology community, please pass this message on to your marketing or marketing communications department or other appropriate group. Please ask them to help support BIOSCI by sponsoring our Web site and explain the uses and benefits of the system to the biology community. If they are interested, they can then contact us for further information at our tech support address, biosci-help@net.bio.net. Our hope is to quickly raise several large corporate/institutional sponsors on our heavily-used WWW locations (some stats appended below), and then end this sponsorship campaign so that our resources can continue to be used for service provision, not fundraising. Many of our specialty newsgroup WWW archives are still used by small communities of scientists (and they haven't been heavily promoted yet). While these may be valuable niche markets to some advertisers, it will generate more labor and overhead having to find these sponsors, fairly price the locations, and deal with lots of smaller sponsorships than fewer mid-to large sponsors. We are striving to keep our operation as lean and efficient as possible since we are not trying to make careers out of running BIOSCI. We are trying if at all possible to avoid the administrative overhead entailed with processing lots of small payments to reach our fundraising goals. I'd like to thank all of you for your help in advance. In helping us, you are also helping yourselves, not only in keeping this resource available for all of the both large and small research communities that we serve, but also by alleviating the need for us to go back and compete with researchers for tight grant dollars! We promised NSF when we were awarded the BIOSCI grant that we would carry out this mission to make the service self-supporting. With your help, we will succeed in continuing BIOSCI's work into its second decade. Thank you very much! Sincerely, Dave Kristofferson BIOSCI/bionet Manager biosci-help@net.bio.net A list of our prime WWW sponsorship locations follow. Statistics are for the four week period from 22 Jan. - 18 Feb. 1996 and usage continues to grow. ---------------------------------------------------------------------- The overall BIOSCI WWW pages are currently visited by users from close to 5000 unique computer hosts per week. Web servers only log the Internet computer/host name and frequently more than one individual can connect to us from a particular host. Main home page, http://www.bio.net, visited recently by about 2100 unique hosts per week Main Newsgroups archives page, http://www.bio.net/archives.html, visited recently by about 1200 Unique hosts per week BIO-JOURNALS archive page, http://www.bio.net/BIO-JOURNALS.html, visited recently by about 1000 unique hosts per week. EMPLOYMENT archive pages: http://www.bio.net:80/hypermail/EMPLOYMENT/ and monthly header pages, visited recently by about 600 unique hosts per week. Address database search page, http://www.bio.net/addrsearch.html, visited recently by about 450 unique hosts per week. Methods newsgroup archive pages, http://www.bio.net:80/hypermail/METHDS- REAGNTS/ and monthly header pages, visited recently by about 350 unique hosts per week. ---------------------------------------------------------------------- From owner-ageing@net.bio.net Tue Apr 02 23:00:00 1996 Path: biosci!daresbury!nntp-trd.UNINETT.no!newsfeed.sunet.se!news01.sunet.se!sunic!mn6.swip.net!plug.news.pipex.net!pipex!tank.news.pipex.net!pipex!iol!imci2!news.internetMCI.com!newsfeed.internetmci.com!uwm.edu!news.sol.net!daily-planet.execpc.com!maureen.execpc.com!user From: cordell@execpc.com (Bruce R. Cordell) Newsgroups: bionet.molbio.ageing Subject: Re: How old should you be before start eating Melatonin? Date: Wed, 03 Apr 1996 14:04:35 -0500 Organization: TSR, Inc. Lines: 24 Distribution: world Message-ID: References: <4je7dr$cie@nyheter.chalmers.se> <4jm7st$poe@nnrp1.news.primenet.com> NNTP-Posting-Host: maureen.execpc.com > Niclas Johansson wrote: > : Well the subject says it all: > : How old should you be before start eating Melatonin? > > : I am 24, is it to early??? > > : Niclas. I'm 27, and I take a quartered 3mg (0.75mg) melatonin supplement every third night. Unlike others I've compared notes with on this topic, I find that larger and more frequent doses leave me feeling sleepy on into the next day. The above stated dosage seems to keep me very well rested, and full of energy thereby. If it has an additional antioxidant effect that allows my body to repair itself above and beyond what consistent quality rest can provide, then I'm a double winner :). _______________________ Bruce R. Cordell, Designer TSR, Inc. (414 248 3625) cordell@execpc.com TSRCordell@aol.com http://www.execpc.com/~cordell ___________________________ From owner-ageing@net.bio.net Wed Apr 03 23:00:00 1996 Path: biosci!CIS.OHIO-STATE.EDU!jj From: jj@CIS.OHIO-STATE.EDU (John Josephson) Newsgroups: bionet.molbio.ageing Subject: Re: Chinese herb to fight aging Date: 4 Apr 1996 10:48:33 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 6 Sender: daemon@net.bio.net Distribution: world Message-ID: <199604041844.OAA09519@columbus.cis.ohio-state.edu> References: <4k1150$1gu@host-3.cyberhighway.net> NNTP-Posting-Host: net.bio.net > I am almost 50, but I still look 25, I found the fountain of youth. OK, I'll bite. Where did you find it? .. jj From owner-ageing@net.bio.net Wed Apr 03 23:00:00 1996 Path: biosci!daresbury!nntp-trd.UNINETT.no!nntp.uio.no!news.cais.net!news.ac.net!imci4!newsfeed.internetmci.com!news.cyberhighway.net!usenet From: jade@cyberhighway.net (Jade) Newsgroups: bionet.molbio.ageing Subject: Chinese herb to fight aging Date: Thu, 04 Apr 1996 17:42:23 GMT Organization: CyberHighway Internet Services Lines: 2 Message-ID: <4k1150$1gu@host-3.cyberhighway.net> NNTP-Posting-Host: portlandpm1-30.cyberhighway.net X-Newsreader: Forte Free Agent 1.0.82 I am almost 50, but I still look 25, I found the fountain of youth. From owner-ageing@net.bio.net Wed Apr 03 23:00:00 1996 Path: biosci!rutgers!gatech!willis.cis.uab.edu!news.ecn.bgu.edu!vixen.cso.uiuc.edu!howland.reston.ans.net!news-e2a.gnn.com!newstf01.news.aol.com!newsbf02.news.aol.com!not-for-mail From: jayzimm@aol.com (JayZimm) Newsgroups: bionet.molbio.ageing Subject: Re: Life extension in rats. Date: 3 Apr 1996 23:36:10 -0500 Organization: America Online, Inc. (1-800-827-6364) Lines: 5 Sender: root@newsbf02.news.aol.com Message-ID: <4jvjjq$6o7@newsbf02.news.aol.com> References: <4jovk8$61m@mother.usf.edu> Reply-To: jayzimm@aol.com (JayZimm) NNTP-Posting-Host: newsbf02.mail.aol.com I recall thet Hochshield (spelling only approximate) fed antioxidants to rats in the mid 1970's, or earlier, and also got a 10% increase in lifespan, but as I recall, there were questions about the statistical significance of such a small effect compared to energy or methionine restriction, which produce 40-50% increases. From owner-ageing@net.bio.net Thu Apr 04 23:00:00 1996 Path: biosci!rutgers!gatech!newsfeed.internetmci.com!newsxfer2.itd.umich.edu!news.eecs.umich.edu!nntp.neu.edu!news3.near.net!yale!news-mail-gateway!daemon From: tree@afn.org (David T. Gray) Newsgroups: bionet.molbio.ageing Subject: DownLoad - ~Net/DownLoad Manager (Latest Version) Date: 5 Apr 1996 08:07:37 -0500 Organization: Yale CS Mail/News Gateway Lines: 27 Sender: daemon@cs.yale.edu Message-ID: <199604051307.HAA09419@phoenix.phoenix.net> NNTP-Posting-Host: babyblue.cs.yale.edu Version "B" is available on the Net at: http://www.phoenix.net/~aquarian/davids/net.html or http://www.afn.org/~tree/net.html The search engine is an offline interrogator of large disorganized text files supporting multiple searches on single files or whole directories for up-to four key words or phrases, simulating hyper-text associations. Hope you enjoy the new version... David ~~~~~~~~~~~~~~~~~~~~~ VISIT MY WEB SITES ~~~~~~~~~~~~~~~~~~~~~ WEB SITES: http://www.phoenix.net/~aquarian/davids/tree.html http://www.afn.org/~tree/tree.html TOPICS: Weighted Asset Model of Real Estate Appraisal Real Estate Investment Software, Reinvest (shareware) My special fondness for the I.R.S. ~Net/DownLoad Manager, shareware Legal Searcher, shareware David's Secrets of Yo-Yo's 477-LIVE, Homes for Rent in Austin, TX Locating lost family members (Adoption Registry) The Transformational Portal ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ David T. Gray at tree@afn.org From owner-ageing@net.bio.net Mon Apr 08 23:00:00 1996 Path: biosci!rutgers!gatech!newsfeed.internetmci.com!in2.uu.net!sun.sirius.com!usenet From: "Cheryl A. Cohen" Newsgroups: bionet.molbio.ageing Subject: Health Education reviewers needed-Geriatric Medicine Date: Tue, 09 Apr 1996 09:41:47 -0700 Organization: Writing for Business Lines: 11 Message-ID: <316A934B.2FCA@sirius.com> NNTP-Posting-Host: ppp031-sf2.sirius.com Mime-Version: 1.0 Content-Type: text/plain; charset=us-ascii Content-Transfer-Encoding: 7bit X-Mailer: Mozilla 2.0 (Win16; I) Hello. I represent a SF Bay Area health education publisher who is seeking MDs and other healthcare professionals to review some short (one page or less) audio scripts on aging. Target audience is the general public. Compensation is provided. For more info, e-mail: cac@sirius.com. Thanks! From owner-ageing@net.bio.net Tue Apr 09 23:00:00 1996 Path: biosci!rutgers!uwm.edu!cs.utexas.edu!swrinde!sgigate.sgi.com!news1.best.com!news.aimnet.com!alpha.sky.net!winternet.com!mr.net!news.mr.net!news.protocom.com!usenet From: rdouglas@product-testing.com (Ray Douglas) Newsgroups: bionet.molbio.ageing Subject: retirement issues Date: 10 Apr 1996 03:44:35 GMT Organization: Protocol Communications, Inc. Lines: 11 Message-ID: <4kfar3$a82@tracy.protocom.com> NNTP-Posting-Host: cs1-2.protocom.com X-Newsreader: WinVN 0.92.6+ I would appreciate any help. I have been searching without much luck for information regarding retirement issues especially for women, low income and minority people. If you happen to know where I could find any information about these issues on the Net, please email me. Much obliged, Ray Douglas rdouglas@product-testing.com From owner-ageing@net.bio.net Tue Apr 09 23:00:00 1996 Path: biosci!rutgers!gatech!newsfeed.internetmci.com!news.zeitgeist.net!news.pixi.com!usenet From: Allan Kanemori Newsgroups: bionet.molbio.ageing Subject: DHEA Date: Tue, 09 Apr 1996 08:46:20 -1000 Organization: Pacific Information eXchange, Inc. Lines: 3 Message-ID: <316AB07C.4656@ohana.com> NNTP-Posting-Host: surfer006.ohana.com Mime-Version: 1.0 Content-Type: text/plain; charset=us-ascii Content-Transfer-Encoding: 7bit X-Mailer: Mozilla 2.01 (Win95; I) Hi. Since Endogen is a better way of obtaining DHEA, what form do health food stores sell this in? From owner-ageing@net.bio.net Tue Apr 09 23:00:00 1996 Path: biosci!hhs.cba.hawaii.edu!JIM From: JIM@hhs.cba.hawaii.edu ("Jim Empure") Newsgroups: bionet.molbio.ageing Subject: discussion group Date: 10 Apr 1996 13:12:28 -0700 Organization: Honolulu Heart Program Lines: 8 Sender: daemon@net.bio.net Distribution: world Message-ID: NNTP-Posting-Host: net.bio.net Am doing research at the Univ. of Hawaii on patients wait listed in acute care hospital beds for nursing home placement. Am looking for previous literature on this topic but have found very little using Medline. Any references? Any suggestions on where to look? Please contact me at my E-mail address. Mahalo! From owner-ageing@net.bio.net Tue Apr 09 23:00:00 1996 Path: biosci!geron.com!mwest From: mwest@geron.com ("Mike West") Newsgroups: bionet.molbio.ageing Subject: FWD>RE>Premature Ageing Date: 10 Apr 1996 15:25:24 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 83 Sender: daemon@net.bio.net Distribution: world Message-ID: NNTP-Posting-Host: net.bio.net Mail*Link( SMTP FWD>RE>Premature Ageing There actually is quite a bit of evidence of a causal connection between telomere loss and cell aging and also cell aging and organismal aging. In regard to the former, or course, telomeres are lost in mortal cells that lack telomerase, immortal cells like the reproductive cells, have abundant telomerase and stable telomeres and when cells immortalize as in cancer they abnormally acquire telomerase acitivity. This is correlative evidence. Recently, U.T. Southwestern published in EMBO J evidence of causality, extending the telomereres of cells increased their replicative capacity as you would predict. In regard to evidence that cell senescence is occuring in vivo, the evidence is seen in many ways. Cells cultured in primary cultures from old people's tissues contain many large nondividing cells that have many markers of cell senescence (morphological, gene tag markers, enzyme markers such as beta gal, and lastly telomere length) For instance in the case of skin, dermal fibroblasts from aged donors turn blue in X-gal as do cells at the Hayflick limit and telomere length has been shown to shorten in the skin with age. When the beta-gal assay was performed on skin sections in situ, blue cells were shown to be present only in donors over the age of 30 or so, and only a percentage (probably less that 50%) were seen to show senescent markers even in very old donors. But this is what many would expect, that is, that cell senescence in a minority of cells can have a dominant effect on tissue metabolism. Personally, I like to say that no one dies of old age, but rather, we die because of disease. But that isn't to say that disease and aging aren't sometimes the same thing. If we defined age-related pathology not as the many pathologies that simply increase in frequency with age, but as pathologies that virtually everone sees manifestations of in advanced age (such as atherosclerosis, AMD, osteoporosis, etc, then maybe, these pathologies are actually the manifestation of aging in that given tissue (i.e. sometimes a senescent cell may be a "sick" cell. -------------------------------------- Date: 4/1/96 2:46 PM From: jpissa@welchlink.welch.jhu.edu Oliver Bogler wrote: >This is all very interesting, but you seem to unaware that there is no evidence of a >connection between telomere length/cellular ageing and organismal ageing. Organismal >ageing is better discussed in terms of mortality - no one dies of "old age". There is >always a "pathology", and that has nothing to do with telomere length. You are right to point out the shortcomings of the current 'Telomere' theory of aging. Nevertheless, it is not entirely clear that no one dies of 'old age'. Autopsy studies indicate that 20-30% of deaths in the elderly cannot be attributed to a specific pathology. While this may certainly be due to missed diagnoses, this proportion of 'unclear' cause of death is higher than that seen in autopsy studies of younger individuals. I think that the notion of dying of 'old age' i.e. because of a limited lifespan that is not disease related remains open for discussion. Any comments anyone ? Jean-Pierre Issa MD Johns Hopkins Oncology Center ------------------ RFC822 Header Follows ------------------ Received: by geron.com with SMTP;1 Apr 1996 14:33:14 -0800 Received: from net.bio.net by mx.smtp.psi.net (8.6.12/SMI-4.1.3-PSI) id RAA13104; Mon, 1 Apr 1996 17:03:41 -0500 Received: (from daemon@localhost) by net.bio.net (8.6.12/8.6.6) id NAA14945; Mon, 1 Apr 1996 13:58:18 -0800 Received: (from news@localhost) by net.bio.net (8.6.12/8.6.6) id NAA14935; Mon, 1 Apr 1996 13:58:15 -0800 To: ageing@net.bio.net From: jpissa@welchlink.welch.jhu.edu (Jean-Pierre Issa) Subject: Re: Premature Ageing Date: Tue, 02 Apr 1996 00:49:28 GMT Message-ID: <3160795b.16167448@news.alt.net> Reply-To: jpissa@welchlink.welch.jhu.edu X-Newsreader: Forte Agent .99d/16.182 From owner-ageing@net.bio.net Tue Apr 09 23:00:00 1996 Path: biosci!geron.com!mwest From: mwest@geron.com ("Mike West") Newsgroups: bionet.molbio.ageing Subject: Telomerase & Aging Date: 10 Apr 1996 15:25:36 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 85 Sender: daemon@net.bio.net Distribution: world Message-ID: NNTP-Posting-Host: net.bio.net Subject: Time: 1:22 PM OFFICE MEMO Telomerase & Aging Date: 4/10/96 In response to Dr. Issa's recent concerns about the telomere-aging connection I offer the following thoughts: His comments were: There are many more good labs studying the telomere/aging connection than you imply. Unfortunately, there are many holes in the (fascinating) speculation that telomere loss 'causes' aging. Some that come to mind: 1- Many normal cells (specially stem cells) express telomerase and thus can repair/replace any significant telomere loss. Comment: The striking thing about telomerase expression which is thought to make cells immortal, is that it is NOT expressed by many cell types. It is clearly abundant in the reproductive cells which obviously allows them to make the species immortal, and abnormally in malignant cells likewise conferring replicative immortality to them, however, it is conspicuously absent in most somatic cells and tissues. It appears to be true that there is a low (<100X less activity) of telomerase in candidate hematapoietic stem cells, but the biology there is not clear and all the evidence suggests that telomeres are being lost with age in vivo in these cells and when the candidate cells are passaged in vitro as well. So clearly the telomerase that is there is not repairing telomere loss. The only normal cells that are known to have stable telomeres are the reproductive cells. (Keratinocyte stem cells may also have low levels, but again, they are not maintaining telomere length) 2- Cells from elderly individuals have not yet reached a 'critical' telomere shortening (which happens if you culture these cells to senescence. Comment: This isn't really true. First, few would suggest that all of the cells in a given tissue would need to reach critical telomere length and the Hayflick limit for pathological consequences too occur. In the immune system, for example, perhaps only <10% of lymphocytes reaching senescence could impair a robust response to a pathogen and lead to a fatal infection. Similar logic would apply to other tissues. In the case of the immune system, lymphocytes are observed to reach the Hayflick limit at about 5-7 kbp terminal restriction fragment length which is interpreted as a "critical length" where perhaps one or more telomeres actually have lost repeats and trigger a cell cycle checkpoint arrest. If you look at the peripheral blood lymphocytes of aging people, you see the TRF length drops to about 5 kbp (the Hayflick limit) in centenarians (Am. J. Hum. Genetics 52: 661). Similar results have been reported for vascular intima, Hematapoietic stem cells (PNAS 91: 9857) etc. 3- Dr. Blackburn (one of the telomere pioneers) has shown that in Tetrahymena (I think, but I may be wrong), telomeres shorten until middle-age, THEN they start elongating again! At the end of these organisms' life span, their telomeres are nearly the same length as when they are born. (PNAS, 1994). Actually paramecia. Yes, maybe the senescence you see in paramecia is caused by another mechanism (though some argue that Dr. Blackburn's data actually support a role for telomere loss in this peculiar type of senescence). It is certainly true that telomere loss appears to play no role in the limited budding capacity of maternal yeast. But, to argue against the telomere hypothesis for mammalian cells based on the fact that paramecia clonal senescence in the absence of conjugation is probably a stretch, don't you think? Thus, the telomere loss - aging connection remains somewhat speculative. It is possible that even a small degree of telomere shortening causes significant changes in gene expression elsewhere in the genome, thus linking it to aging, but I do not think this has been firmly demonstrated yet. Comment: I think everyone would agree that the hypothesis is still "young" but the amazing thing to me is the breadth of data pouring in to support it (such as the recent EMBO J paper showing a direct causal connection e.g. lengthening telomeres increases the replicative lifespan of cells) and the predictive power of the theory. But I assure you, much research into telomere length and aging is going on ! Comment: A lot, especially in the telomerase-cancer connection. -MWest Regards, Jean-Pierre Issa, MD Johns Hopkins Oncology Center From owner-ageing@net.bio.net Wed Apr 10 23:00:00 1996 Path: biosci!agate!spool.mu.edu!daily-planet.execpc.com!news.sol.net!news.inc.net!uwm.edu!fnnews.fnal.gov!nntp-server.caltech.edu!nntp1.jpl.nasa.gov!news.alt.net!newspost1.alt.net!usenet From: jpissa@welchlink.welch.jhu.edu (Jean-Pierre Issa) Newsgroups: bionet.molbio.ageing Subject: Re: FWD>RE>Premature Ageing Date: Thu, 11 Apr 1996 20:49:10 GMT Organization: j Lines: 63 Message-ID: <316d662f.17024113@news.alt.net> References: Reply-To: jpissa@welchlink.welch.jhu.edu X-Newsreader: Forte Agent .99d/16.182 mwest@geron.com ("Mike West") wrote: (Snip) About Telomeres and aging > This is correlative evidence. >Recently, U.T. Southwestern published in EMBO J evidence of causality, >extending the telomereres of cells increased their replicative capacity as you >would predict. I have not yet seen this paper, although I have heard some of this data before (is it out yet?, could you summarize it for us?). This is very interesting but, as I am sure you know, there is still some controversy over whether replicative senescence (the Hayflick limit) truly reflects in-vivo aging. > >In regard to evidence that cell senescence is occuring in vivo, the evidence >is seen in many ways. Cells cultured in primary cultures from old people's >tissues contain many large nondividing cells that have many markers of cell >senescence (morphological, gene tag markers, enzyme markers such as beta gal, >and lastly telomere length) For instance in the case of skin, dermal >fibroblasts from aged donors turn blue in X-gal as do cells at the Hayflick >limit and telomere length has been shown to shorten in the skin with age. >When the beta-gal assay was performed on skin sections in situ, blue cells >were shown to be present only in donors over the age of 30 or so, and only a >percentage (probably less that 50%) were seen to show senescent markers even >in very old donors. But this is what many would expect, that is, that cell >senescence in a minority of cells can have a dominant effect on tissue >metabolism. The pictures I have seen suggest that less than 10% of aged skin cells stain positive for beta-gal. I think this is fairly recent data, and I have not seen the published papers on this subject. Nevertheless, much of aging physiology is difficult to explain by loss of function in a minority of cells. For example, changes in cardiac contractility, vascular reactivity, pulmonary compliance etc... appear fairly extensive. In addition, many organs can tolerate loss of a considerable fraction of cells without gross physiologic consequences (think of a unilateral nephrectomy: 50% cell loss without much immediate effects. >Personally, I like to say that no one dies of old age, but rather, we die >because of disease. But that isn't to say that disease and aging aren't >sometimes the same thing. If we defined age-related pathology not as the many >pathologies that simply increase in frequency with age, but as pathologies >that virtually everone sees manifestations of in advanced age (such as >atherosclerosis, AMD, osteoporosis, etc, then maybe, these pathologies are >actually the manifestation of aging in that given tissue (i.e. sometimes a >senescent cell may be a "sick" cell. Well, yes and know: I agree that a senescent cell may be a 'sick' cell. But many of the 'aging' diseases you mention are not simply a reflection of advanced age. Take atherosclerosis, the #1 killer in developed countries: Atherosclerosis is almost unheard of in non-human mammals in the wild, yet they age and 'die of old age'. Similarly, human tribes that have a drastically different diet (no NaCl, high KCl, high melatonin - just kidding) have a low incidence of atherosclerosis, yet... they still die at an advanced age. As mentioned in my previous post, some autopsies in older people do not detect atherosclerosis or significant pathology. I believe, as you probably do, that there is more to human aging than an accumulation of diseases. I wish I knew, however, what this 'more' is ! BTW, what is AMD ? From owner-ageing@net.bio.net Wed Apr 10 23:00:00 1996 Path: biosci!agate!spool.mu.edu!usenet.eel.ufl.edu!news.alt.net!newspost1.alt.net!usenet From: jpissa@welchlink.welch.jhu.edu (Jean-Pierre Issa) Newsgroups: bionet.molbio.ageing Subject: Re: Telomerase & Aging Date: Thu, 11 Apr 1996 21:40:53 GMT Organization: j Lines: 113 Message-ID: <316d7054.19621352@news.alt.net> References: Reply-To: jpissa@welchlink.welch.jhu.edu X-Newsreader: Forte Agent .99d/16.182 mwest@geron.com ("Mike West") wrote: > Subject: Time: 1:22 PM > OFFICE MEMO Telomerase & Aging Date: 4/10/96 What office? :) If you don't mind me asking, do you work at Geron ? > >In response to Dr. Issa's recent concerns about the telomere-aging connection >I offer the following thoughts: No need to be formal: This is Usenet. Call me Jean-Pierre. >Comment: The striking thing about telomerase expression which is thought to >make cells immortal, is that it is NOT expressed by many cell types. It is >clearly abundant in the reproductive cells which obviously allows them to make >the species immortal, and abnormally in malignant cells likewise conferring >replicative immortality to them, however, it is conspicuously absent in most >somatic cells and tissues. It appears to be true that there is a low (<100X >less activity) of telomerase in candidate hematapoietic stem cells, but the >biology there is not clear and all the evidence suggests that telomeres are >being lost with age in vivo in these cells and when the candidate cells are >passaged in vitro as well. So clearly the telomerase that is there is not >repairing telomere loss. The only normal cells that are known to have stable >telomeres are the reproductive cells. (Keratinocyte stem cells may also have >low levels, but again, they are not maintaining telomere length) I do not have the paper in front of me, but I thought that peripheral blood lymphocytes had about 10% of the telomerase activity seen in some tumors. Also, I heard that stem cells from several different organs have easily detectable telomerase activity. (Certainly, all these cells have abundant telomere RNA as recently shown by Greider et al. and others). Stem cells, to my knowledge, cannot be passaged in-vitro (the committed progeny quickly takes over the cultures). Thus, I am not sure that stem cells still lose telomere length with age (correct me if I am wrong...). Still, why do aging tissues lose telomere length if stem cells express telomerase ? Obviously, I don't know. Since 'committed' cells lose telomerase activity, subsequent generations derived from these cells will have shorter telomeres.Is it possible then that the loss of telomere length in aging tissues reflects a changing ratio of stem cells-early progenitors to late progenitors-differentiated cells ? have I confused everybody ? (snip) >Comment: This isn't really true. First, few would suggest that all of the >cells in a given tissue would need to reach critical telomere length and the >Hayflick limit for pathological consequences too occur. In the immune system, >for example, perhaps only <10% of lymphocytes reaching senescence could impair >a robust response to a pathogen and lead to a fatal infection. Similar logic >would apply to other tissues. Yes and no... see my other post in this thread. > In the case of the immune system, lymphocytes >are observed to reach the Hayflick limit at about 5-7 kbp terminal restriction >fragment length which is interpreted as a "critical length" where perhaps one >or more telomeres actually have lost repeats and trigger a cell cycle >checkpoint arrest. If you look at the peripheral blood lymphocytes of aging >people, you see the TRF length drops to about 5 kbp (the Hayflick limit) in >centenarians (Am. J. Hum. Genetics 52: 661). Similar results have been >reported for vascular intima, Hematapoietic stem cells (PNAS 91: 9857) etc. Please don't take my next remarks in a negative way: They are solely for discussion purposes - I do believe telomeres are important ! Nevertheless, the length of telomeres in peripheral blood lymphocytes is not directly relevant to aging: These cells, for the most part, do not divide... It may be relevant to gene expression changes and/or genetic instability, but that remains to be demonstrated. As mentioned above, what is critical to in vivo senescence / loss of replicative ability is telomere length in stem cells. the PNAS paper you reference is great. Nonetheless, to my knowledge, most stem cell biologists believe that the 'true' stem cell is not necessarily the CD34+ CD38lo fraction they studied. Primitive hematopoietic cells yes, stem cells, probably not. Furthermore, as mentioned above, the 'stem cell' is thought to be an essentially dormant cell. In culture, it quickly is taken over by committed cells. Before you ask, I believe the 'true' stem cell is this very rare cell that is required for regenerating a lethally irradiated bone marrow, and that is (perhaps) immortal. the PNAS paper, however makes several important points relevant to this discussion: In the same individual, telomere length is greater in primitive hematopoietic cells than in differentiated cells. It is therefore probably even greater in the 'true' stem cell... See above for implications of this finding. Furthermore, in the paper, there seems to be very little difference in telomere length between the bone marrow of a 19 yr old, and the bone marrow of a 59 yr old... this begs the question: is telomere length simply a reflection of differentiated status rather than age ? (again, see above). (Snip) > But, to argue against the telomere >hypothesis for mammalian cells based on the fact that paramecia clonal >senescence in the absence of conjugation is probably a stretch, don't you >think? Absolutely. Still, as I understand it, the relation between telomere length and age is also confusing in rodents (am I wrong ?). Doesn't this trouble you ? Anyone knows of a telomere length / aging connection in primates? (Snip) >But I assure you, much research into telomere length and aging is >going on ! >>Comment: A lot, especially in the telomerase-cancer connection. More research is good ! But, let's not get started on the telomerase-cancer connection ! :) Thank you for a good discussion. Jean-Pierre Issa From owner-ageing@net.bio.net Wed Apr 10 23:00:00 1996 Path: biosci!TENET.EDU!dashley From: dashley@TENET.EDU (Don Ashley) Newsgroups: bionet.molbio.ageing Subject: Cure AGE and AIDS Date: 11 Apr 1996 02:05:52 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 100 Sender: daemon@net.bio.net Distribution: world Message-ID: References: NNTP-Posting-Host: net.bio.net Ageing/AIDS similarity: On 10 Apr 1996, Mike West wrote: > Mail*Link( SMTP FWD>RE>Premature Ageing > > There actually is quite a bit of evidence of a causal connection between > telomere loss and cell aging and also cell aging and organismal aging. In > regard to the former, or course, telomeres are lost in mortal cells that lack > telomerase, immortal cells like the reproductive cells, have abundant > telomerase and stable telomeres and when cells immortalize as in cancer they > abnormally acquire telomerase acitivity. This is correlative evidence. > Recently, U.T. Southwestern published in EMBO J evidence of causality, > extending the telomereres of cells increased their replicative capacity as you > would predict. > > In regard to evidence that cell senescence is occuring in vivo, the evidence > is seen in many ways. Cells cultured in primary cultures from old people's > tissues contain many large nondividing cells that have many markers of cell > senescence (morphological, gene tag markers, enzyme markers such as beta gal, > and lastly telomere length) For instance in the case of skin, dermal > fibroblasts from aged donors turn blue in X-gal as do cells at the Hayflick > limit and telomere length has been shown to shorten in the skin with age. > When the beta-gal assay was performed on skin sections in situ, blue cells > were shown to be present only in donors over the age of 30 or so, and only a > percentage (probably less that 50%) were seen to show senescent markers even > in very old donors. But this is what many would expect, that is, that cell > senescence in a minority of cells can have a dominant effect on tissue > metabolism. > > Personally, I like to say that no one dies of old age, but rather, we die > because of disease. This sounds like AIDS. Curing AIDS and AGE have common objectives. AIDS gets more publicity and support from the media, however, as well as from the general public. Why is that? Why is there so much more hype about AIDS than AGE? AIDS just works a few years quicker. Those interested in AGE research may consider the political and promotional strategies of the proponents of AIDS research. Alert the media. Alarm the public. Light a fire. > But that isn't to say that disease and aging aren't > sometimes the same thing. If we defined age-related pathology not as the many > pathologies that simply increase in frequency with age, but as pathologies > that virtually everone sees manifestations of in advanced age (such as > atherosclerosis, AMD, osteoporosis, etc, then maybe, these pathologies are > actually the manifestation of aging in that given tissue (i.e. sometimes a > senescent cell may be a "sick" cell. > > -------------------------------------- > Date: 4/1/96 2:46 PM > From: jpissa@welchlink.welch.jhu.edu > Oliver Bogler wrote: > > > >This is all very interesting, but you seem to unaware that there is no > evidence of a > >connection between telomere length/cellular ageing and organismal ageing. > Organismal > >ageing is better discussed in terms of mortality - no one dies of "old age". > There is > >always a "pathology", and that has nothing to do with telomere length. > > > You are right to point out the shortcomings of the current 'Telomere' > theory of aging. Nevertheless, it is not entirely clear that no one > dies of 'old age'. Autopsy studies indicate that 20-30% of deaths in > the elderly cannot be attributed to a specific pathology. While this > may certainly be due to missed diagnoses, this proportion of 'unclear' > cause of death is higher than that seen in autopsy studies of younger > individuals. I think that the notion of dying of 'old age' i.e. > because of a limited lifespan that is not disease related remains open > for discussion. Any comments anyone ? > > Jean-Pierre Issa MD > Johns Hopkins Oncology Center > > > > ------------------ RFC822 Header Follows ------------------ > Received: by geron.com with SMTP;1 Apr 1996 14:33:14 -0800 > Received: from net.bio.net by mx.smtp.psi.net (8.6.12/SMI-4.1.3-PSI) > id RAA13104; Mon, 1 Apr 1996 17:03:41 -0500 > Received: (from daemon@localhost) by net.bio.net (8.6.12/8.6.6) id NAA14945; > Mon, 1 Apr 1996 13:58:18 -0800 > Received: (from news@localhost) by net.bio.net (8.6.12/8.6.6) id NAA14935; > Mon, 1 Apr 1996 13:58:15 -0800 > To: ageing@net.bio.net > From: jpissa@welchlink.welch.jhu.edu (Jean-Pierre Issa) > Subject: Re: Premature Ageing > Date: Tue, 02 Apr 1996 00:49:28 GMT > Message-ID: <3160795b.16167448@news.alt.net> > Reply-To: jpissa@welchlink.welch.jhu.edu > X-Newsreader: Forte Agent .99d/16.182 > > > > > From owner-ageing@net.bio.net Wed Apr 10 23:00:00 1996 Path: biosci!TENET.EDU!dashley From: dashley@TENET.EDU (Don Ashley) Newsgroups: bionet.molbio.ageing Subject: Re: Telomerase & Aging Date: 11 Apr 1996 01:50:19 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 98 Sender: daemon@net.bio.net Distribution: world Message-ID: References: NNTP-Posting-Host: net.bio.net This is a request for a source and summary of the EMBO J paper cited below showing the relationship of telomere length to replicative lifespan of cells. Thanks....Don Ashley, Houston On 10 Apr 1996, Mike West wrote: > Subject: Time: 1:22 PM > OFFICE MEMO Telomerase & Aging Date: 4/10/96 > > In response to Dr. Issa's recent concerns about the telomere-aging connection > I offer the following thoughts: > > His comments were: > > There are many more good labs studying the telomere/aging connection > than you imply. Unfortunately, there are many holes in the > (fascinating) speculation that telomere loss 'causes' aging. Some that > come to mind: > 1- Many normal cells (specially stem cells) express telomerase and > thus can repair/replace any significant telomere loss. > > Comment: The striking thing about telomerase expression which is thought to > make cells immortal, is that it is NOT expressed by many cell types. It is > clearly abundant in the reproductive cells which obviously allows them to make > the species immortal, and abnormally in malignant cells likewise conferring > replicative immortality to them, however, it is conspicuously absent in most > somatic cells and tissues. It appears to be true that there is a low (<100X > less activity) of telomerase in candidate hematapoietic stem cells, but the > biology there is not clear and all the evidence suggests that telomeres are > being lost with age in vivo in these cells and when the candidate cells are > passaged in vitro as well. So clearly the telomerase that is there is not > repairing telomere loss. The only normal cells that are known to have stable > telomeres are the reproductive cells. (Keratinocyte stem cells may also have > low levels, but again, they are not maintaining telomere length) > > 2- Cells from elderly individuals have not yet reached a 'critical' > telomere shortening (which happens if you culture these cells to > senescence. > > Comment: This isn't really true. First, few would suggest that all of the > cells in a given tissue would need to reach critical telomere length and the > Hayflick limit for pathological consequences too occur. In the immune system, > for example, perhaps only <10% of lymphocytes reaching senescence could impair > a robust response to a pathogen and lead to a fatal infection. Similar logic > would apply to other tissues. In the case of the immune system, lymphocytes > are observed to reach the Hayflick limit at about 5-7 kbp terminal restriction > fragment length which is interpreted as a "critical length" where perhaps one > or more telomeres actually have lost repeats and trigger a cell cycle > checkpoint arrest. If you look at the peripheral blood lymphocytes of aging > people, you see the TRF length drops to about 5 kbp (the Hayflick limit) in > centenarians (Am. J. Hum. Genetics 52: 661). Similar results have been > reported for vascular intima, Hematapoietic stem cells (PNAS 91: 9857) etc. > > 3- Dr. Blackburn (one of the telomere pioneers) has shown that in > Tetrahymena (I think, but I may be wrong), telomeres shorten until > middle-age, THEN they start elongating again! At the end of these > organisms' life span, their telomeres are nearly the same length as > when they are born. (PNAS, 1994). > > Actually paramecia. Yes, maybe the senescence you see in paramecia is caused > by another mechanism (though some argue that Dr. Blackburn's data actually > support a role for telomere loss in this peculiar type of senescence). It is > certainly true that telomere loss appears to play no role in the limited > budding capacity of maternal yeast. But, to argue against the telomere > hypothesis for mammalian cells based on the fact that paramecia clonal > senescence in the absence of conjugation is probably a stretch, don't you > think? > > Thus, the telomere loss - aging connection remains somewhat > speculative. It is possible that even a small degree of telomere > shortening causes significant changes in gene expression elsewhere in > the genome, thus linking it to aging, but I do not think this has been > firmly demonstrated yet. > > Comment: I think everyone would agree that the hypothesis is still "young" > but the amazing thing to me is the breadth of data pouring in to support it > (such as the recent EMBO J paper showing a direct causal connection e.g. lengthening > telomeres increases the replicative lifespan of cells) and the predictive > power of the theory. Please summarize and give source of the EMBO J paper.....Don > > But I assure you, much research into telomere length and aging is > going on ! > > Comment: A lot, especially in the telomerase-cancer connection. > > -MWest > > Regards, > Jean-Pierre Issa, MD > Johns Hopkins Oncology Center > > > From owner-ageing@net.bio.net Wed Apr 10 23:00:00 1996 Path: biosci!daresbury!bioftp.unibas.ch!infobiogen.fr!pasteur.fr!univ-lyon1.fr!in2p3.fr!swidir.switch.ch!swsbe6.switch.ch!surfnet.nl!howland.reston.ans.net!newsfeed.internetmci.com!in1.uu.net!news.alt.net!newspost1.alt.net!usenet From: jpissa@welchlink.welch.jhu.edu (Jean-Pierre Issa) Newsgroups: bionet.molbio.ageing Subject: Re: Telomere questions Date: Thu, 11 Apr 1996 21:50:50 GMT Organization: j Lines: 42 Message-ID: <316d7c80.22736698@news.alt.net> References: <4kibg4$kp2@sp115.ocs.lsu.edu> Reply-To: jpissa@welchlink.welch.jhu.edu X-Newsreader: Forte Agent .99d/16.182 grant@bit.csc.lsu.edu (Kevin Paul Grant) wrote: >Admittedly it is far too early to peg telomere shortening (loss? I don't >know the proper terminology here) as the cause of ageing, but from what >I read on the net there would seem to be a strong connection. Two >questions come to my mind. First, is there some material that a >person like myself (not a biology major) can read and understand on >the subject? Check recent issues of Scientific American. I saw a reference to a review there by Dr. Greider et al. > Second, to date, has any method been found that >prevents or significantly slows down the rate of telomere shortening? None published ! >It seems to me that the latter might place you in a bit higher risk of >cancer than otherwise though. Maybe. But don't tell that to drug companies... >Recently I saw a TV interview in which some Ph.D. or other said that >many cells in the human body were effectlively immortal. Do these >cells (if this is true) achieve this via prevention of telomere >shortening, and if so (and this is the big question here) do these >kinds of cells show a greater tendency to go cancerous than other >types of cells? If not, what prevents this? It is true, some Stem Cells (the cells responsible for regularly replacing and renewing most human tissues) may be immortal. The telomerase connection there is under investigation (see the premature aging thread in this newsgroup). Some people believe that all cancers arise from stem cells. This, however, is fairly controversial... >All of this assumes that my questions are not so off base as to make >no sense at all... Makes a lot of sense to me... Jean-Pierre Issa From owner-ageing@net.bio.net Wed Apr 10 23:00:00 1996 Path: biosci!geron.com!mwest From: mwest@geron.com ("Mike West") Newsgroups: bionet.molbio.ageing Subject: FWD>RE>Telomerase & Aging Date: 11 Apr 1996 14:56:37 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 140 Sender: daemon@net.bio.net Distribution: world Message-ID: NNTP-Posting-Host: net.bio.net Mail*Link( SMTP FWD>RE>Telomerase & Aging Article is titled "Experimental elongation of telomeres extends the lifespan of immortal X normal cell hybrids" and appeared in the March 15th 1996 issue of EMBO J. vol. 15 (sorry I don't have page numbers). First author is Wright, W.E. -------------------------------------- Date: 4/11/96 7:01 AM From: Don Ashley This is a request for a source and summary of the EMBO J paper cited below showing the relationship of telomere length to replicative lifespan of cells. Thanks....Don Ashley, Houston On 10 Apr 1996, Mike West wrote: > Subject: Time: 1:22 PM > OFFICE MEMO Telomerase & Aging Date: 4/10/96 > > In response to Dr. Issa's recent concerns about the telomere-aging connection > I offer the following thoughts: > > His comments were: > > There are many more good labs studying the telomere/aging connection > than you imply. Unfortunately, there are many holes in the > (fascinating) speculation that telomere loss 'causes' aging. Some that > come to mind: > 1- Many normal cells (specially stem cells) express telomerase and > thus can repair/replace any significant telomere loss. > > Comment: The striking thing about telomerase expression which is thought to > make cells immortal, is that it is NOT expressed by many cell types. It is > clearly abundant in the reproductive cells which obviously allows them to make > the species immortal, and abnormally in malignant cells likewise conferring > replicative immortality to them, however, it is conspicuously absent in most > somatic cells and tissues. It appears to be true that there is a low (<100X > less activity) of telomerase in candidate hematapoietic stem cells, but the > biology there is not clear and all the evidence suggests that telomeres are > being lost with age in vivo in these cells and when the candidate cells are > passaged in vitro as well. So clearly the telomerase that is there is not > repairing telomere loss. The only normal cells that are known to have stable > telomeres are the reproductive cells. (Keratinocyte stem cells may also have > low levels, but again, they are not maintaining telomere length) > > 2- Cells from elderly individuals have not yet reached a 'critical' > telomere shortening (which happens if you culture these cells to > senescence. > > Comment: This isn't really true. First, few would suggest that all of the > cells in a given tissue would need to reach critical telomere length and the > Hayflick limit for pathological consequences too occur. In the immune system, > for example, perhaps only <10% of lymphocytes reaching senescence could impair > a robust response to a pathogen and lead to a fatal infection. Similar logic > would apply to other tissues. In the case of the immune system, lymphocytes > are observed to reach the Hayflick limit at about 5-7 kbp terminal restriction > fragment length which is interpreted as a "critical length" where perhaps one > or more telomeres actually have lost repeats and trigger a cell cycle > checkpoint arrest. If you look at the peripheral blood lymphocytes of aging > people, you see the TRF length drops to about 5 kbp (the Hayflick limit) in > centenarians (Am. J. Hum. Genetics 52: 661). Similar results have been > reported for vascular intima, Hematapoietic stem cells (PNAS 91: 9857) etc. > > 3- Dr. Blackburn (one of the telomere pioneers) has shown that in > Tetrahymena (I think, but I may be wrong), telomeres shorten until > middle-age, THEN they start elongating again! At the end of these > organisms' life span, their telomeres are nearly the same length as > when they are born. (PNAS, 1994). > > Actually paramecia. Yes, maybe the senescence you see in paramecia is caused > by another mechanism (though some argue that Dr. Blackburn's data actually > support a role for telomere loss in this peculiar type of senescence). It is > certainly true that telomere loss appears to play no role in the limited > budding capacity of maternal yeast. But, to argue against the telomere > hypothesis for mammalian cells based on the fact that paramecia clonal > senescence in the absence of conjugation is probably a stretch, don't you > think? > > Thus, the telomere loss - aging connection remains somewhat > speculative. It is possible that even a small degree of telomere > shortening causes significant changes in gene expression elsewhere in > the genome, thus linking it to aging, but I do not think this has been > firmly demonstrated yet. > > Comment: I think everyone would agree that the hypothesis is still "young" > but the amazing thing to me is the breadth of data pouring in to support it > (such as the recent EMBO J paper showing a direct causal connection e.g. lengthening > telomeres increases the replicative lifespan of cells) and the predictive > power of the theory. Please summarize and give source of the EMBO J paper.....Don > > But I assure you, much research into telomere length and aging is > going on ! > > Comment: A lot, especially in the telomerase-cancer connection. > > -MWest > > Regards, > Jean-Pierre Issa, MD > Johns Hopkins Oncology Center > > > ------------------ RFC822 Header Follows ------------------ Received: by geron.com with SMTP;11 Apr 1996 02:12:29 -0700 Received: from net.bio.net by mx2.smtp.psi.net (8.7.5/SMI-5.4-PSI) id EAA01298; Thu, 11 Apr 1996 04:58:00 -0400 (EDT) Received: (from daemon@localhost) by net.bio.net (8.6.12/8.6.6) id BAA14042; Thu, 11 Apr 1996 01:50:43 -0700 Received: (from news@localhost) by net.bio.net (8.6.12/8.6.6) id BAA14036; Thu, 11 Apr 1996 01:50:38 -0700 To: ageing@net.bio.net From: dashley@tenet.edu (Don Ashley) Subject: Re: Telomerase & Aging Date: 11 Apr 1996 01:50:19 -0700 Sender: daemon@net.bio.net Message-ID: NNTP-Posting-Host: net.bio.net From owner-ageing@net.bio.net Wed Apr 10 23:00:00 1996 Path: biosci!geron.com!mwest From: mwest@geron.com ("Mike West") Newsgroups: bionet.molbio.ageing Subject: FWD>RE>FWD>RE>Premature Age Date: 11 Apr 1996 15:45:10 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 98 Sender: daemon@net.bio.net Distribution: world Message-ID: NNTP-Posting-Host: net.bio.net Mail*Link( SMTP FWD>RE>FWD>RE>Premature Ageing >Recently, U.T. Southwestern published in EMBO J evidence of causality, >extending the telomereres of cells increased their replicative capacity as you >would predict. I have not yet seen this paper, although I have heard some of this data before (is it out yet?, could you summarize it for us?). They reported that extending the telomere length in mortal hybrids of normal skin fibroblasts and the reversible immortal cell line IDH4 (the hybrid being mortal and losing telomeres with cell division) increased the replicative lifespan of the cells. This is the only way yet thought of to test the telomere hypothesis in regard to telomere loss causing cell senescence and the results were positive. The flip side of the coin, does inhibiting telomerase in an immortal cell lead to telomere loss and a delayed cell death, has already been demonstrated and published in human cells (Science 269: 1236-1241), and previously in tetrahymena and yeast. This is very interesting but, as I am sure you know, there is still some controversy over whether replicative senescence (the Hayflick limit) truly reflects in-vivo aging. >Yes, but I would suggest that there is growing evidence that senescent cells are an increasing percentage of the cells in various tissues as a function of age, and studies of the altered gene expression of senescent cells suggest that these cells could have a dominant effect on age-related changes in tissue, (e.g. the marked elevation of collagenase activity in senescent fibroblasts could result in the observed age-related loss of dermal collagen with age (Arch Dermatol. 130: 87-95). The pictures I have seen suggest that less than 10% of aged skin cells stain positive for beta-gal. I think this is fairly recent data, and I have not seen the published papers on this subject. Nevertheless, much of aging physiology is difficult to explain by loss of function in a minority of cells. For example, changes in cardiac contractility, vascular reactivity, pulmonary compliance etc... appear fairly extensive. In addition, many organs can tolerate loss of a considerable fraction of cells without gross physiologic consequences (think of a unilateral nephrectomy: 50% cell loss without much immediate effects. I agree that the age-dependent loss of myocardial function probably reflects muscle loss by vascular insufficiency or loss from other causes than cell senescence since the myocardium is postmitotic in the adult and has no stem cells. I doubt that anyone would suggest that all pathology is directly linked to cell senescence. But one could argue that loss of myocardium through ischemia is indirectly caused by atherosclerosis, which may in turn be (in part) caused by the senescence of the endothelium. This is actually an interesting possibility since telomeres are observed to shorten with age in the intima, and particularly in vessels where atherosclerosis is observed. Also, the role of endothelial injury in the early stages of athero is now well accepted, and accelerated cell turnover of endothelial cells is seen in association with the diseased regions. In addition, changes in gene expression of senescent endothelial cells (such as increased ICAM-1) have been reported that are consistent with the cells playing a role in pathogenesis. In regard to other tissues, such as vascular compliance and changes in pulmonary function, the alterations in gene expression with cell senescence are frequently just the types of changes that could play a role in these disorders. For instance, in senile emphysema (and aneurysms), the culprit is thought to be elastolytic proteases, and these are markedy increased in senescent cells. Well, yes and know: I agree that a senescent cell may be a 'sick' cell. But many of the 'aging' diseases you mention are not simply a reflection of advanced age. Take atherosclerosis, the #1 killer in developed countries: Atherosclerosis is almost unheard of in non-human mammals in the wild, yet they age and 'die of old age'. Similarly, human tribes that have a drastically different diet (no NaCl, high KCl, high melatonin - just kidding) have a low incidence of atherosclerosis, yet... they still die at an advanced age. As mentioned in my previous post, some autopsies in older people do not detect atherosclerosis or significant pathology. I believe, as you probably do, that there is more to human aging than an accumulation of diseases. I wish I knew, however, what this 'more' is ! BTW, what is AMD ? Primates, such as rhesus are observed to age in a manner very analogous to humans, e.g. athero, alzheimers, etc. In regard to humans, in speaking with pathologists, I'll give the example of Tom Norwood in Seattle, a card carrying pathologist and gerontologist, he has represented to me that out of hundreds of autopsies, he has bascially never seen an elderly person in the U.S. that didn't have atherosclerosis somewhere in their vascular tree. Yes, maybe alterations in diet may impact the disease progression, but it is hard to maintain that in the U.S. that has one of the best records for nutrition in the world, that all of our citizens are abnormal in regard to an atherogenic diet. But the point was really to suggest that in framing these basic (almost philosophical) questions about what is aging and what is disease, maybe it is helpful in part to recognize that there are some age-related diseases that occur in virtually everone with age, such as athero, AMD (Age-related macular degeneration), osteoporosis, etc. Maybe a focus on these diseases and their etiology may provide valuable insight into the relationship between aging and disease. -MWest From owner-ageing@net.bio.net Wed Apr 10 23:00:00 1996 Path: biosci!geron.com!mwest From: mwest@geron.com ("Mike West") Newsgroups: bionet.molbio.ageing Subject: FWD>Telomere questions Date: 11 Apr 1996 16:13:07 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 58 Sender: daemon@net.bio.net Distribution: world Message-ID: NNTP-Posting-Host: net.bio.net Mail*Link( SMTP FWD>Telomere questions Date: 4/11/96 1:41 AM From: Kevin Paul Grant Admittedly it is far too early to peg telomere shortening (loss? I don't know the proper terminology here) as the cause of ageing, but from what I read on the net there would seem to be a strong connection. Two questions come to my mind. First, is there some material that a person like myself (not a biology major) can read and understand on the subject? Second, to date, has any method been found that prevents or significantly slows down the rate of telomere shortening? It seems to me that the latter might place you in a bit higher risk of cancer than otherwise though. Some recent reviews would be: "Time, telomeres and tumours: Is cellular senescence more than an anticancer mechanism?" Trends in Cell Biology 5: 293-297. "Telomeres and Aging: Fact, Fancy, and the Future" J. NIH Research Feb 22, 1995. also, Michael Fossel recently wrote a popular book on the subject of telomeres called "Reversing Human Aging" William Morrow & Co, 1996. Recently I saw a TV interview in which some Ph.D. or other said that many cells in the human body were effectlively immortal. Do these cells (if this is true) achieve this via prevention of telomere shortening, and if so (and this is the big question here) do these kinds of cells show a greater tendency to go cancerous than other types of cells? If not, what prevents this? One cell type probably is for sure, that is the reproductive cells in the testes. Sperm telomere length is very long and does not appear to shorten with age. This is consistent with the old idea that the species continues from generation to generation because the germ line (reproductive cells) don't share some properties of the rest of the cells in our body that age. Nevertheless, as you say, we don't get lots of testicular cancer, so as you point out, telomerase may be necessary for many cancers, but it may not be sufficient. ------------------ RFC822 Header Follows ------------------ Received: by geron.com with SMTP;11 Apr 1996 01:08:46 -0700 Received: from net.bio.net by mx.smtp.psi.net (8.6.12/SMI-4.1.3-PSI) id EAA07152; Thu, 11 Apr 1996 04:03:16 -0400 Received: (from daemon@localhost) by net.bio.net (8.6.12/8.6.6) id AAA07588; Thu, 11 Apr 1996 00:50:24 -0700 Received: (from news@localhost) by net.bio.net (8.6.12/8.6.6) id AAA07583; Thu, 11 Apr 1996 00:50:23 -0700 To: ageing@net.bio.net From: grant@bit.csc.lsu.edu (Kevin Paul Grant) Subject: Telomere questions Date: 11 Apr 1996 07:14:12 GMT Message-ID: <4kibg4$kp2@sp115.ocs.lsu.edu> NNTP-Posting-Host: bit.csc.lsu.edu From owner-ageing@net.bio.net Wed Apr 10 23:00:00 1996 Path: biosci!rutgers!uwm.edu!cs.utexas.edu!howland.reston.ans.net!vixen.cso.uiuc.edu!newsfeed.internetmci.com!news.msfc.nasa.gov!info.uah.edu!news.lsu.edu!sp115.ocs.lsu.edu!grant From: grant@bit.csc.lsu.edu (Kevin Paul Grant) Newsgroups: bionet.molbio.ageing Subject: Telomere questions Date: 11 Apr 1996 07:14:12 GMT Organization: Department of Computer Science, LSU, Baton Rouge Lines: 23 Message-ID: <4kibg4$kp2@sp115.ocs.lsu.edu> NNTP-Posting-Host: bit.csc.lsu.edu Admittedly it is far too early to peg telomere shortening (loss? I don't know the proper terminology here) as the cause of ageing, but from what I read on the net there would seem to be a strong connection. Two questions come to my mind. First, is there some material that a person like myself (not a biology major) can read and understand on the subject? Second, to date, has any method been found that prevents or significantly slows down the rate of telomere shortening? It seems to me that the latter might place you in a bit higher risk of cancer than otherwise though. Recently I saw a TV interview in which some Ph.D. or other said that many cells in the human body were effectlively immortal. Do these cells (if this is true) achieve this via prevention of telomere shortening, and if so (and this is the big question here) do these kinds of cells show a greater tendency to go cancerous than other types of cells? If not, what prevents this? All of this assumes that my questions are not so off base as to make no sense at all... Thanks, Kevin grant@bit.csc.lsu.edu From owner-ageing@net.bio.net Thu Apr 11 23:00:00 1996 Path: biosci!galaxy.ucr.edu!library.ucla.edu!info.ucla.edu!newsfeed.internetmci.com!news.compuserve.com!news.production.compuserve.com!news From: Jan Czekajewski Ph.D. <75144.2413@CompuServe.COM> Newsgroups: bionet.microbiology,bionet.molbio.ageing,bionet.organisms.schistosoma,sci.bio.microbiology,sci.environment Subject: DEVICE FOR TESTING MAD COW Date: 12 Apr 1996 13:20:16 GMT Organization: Columbus Instruments Lines: 17 Message-ID: <4kllag$3et$1@mhafc.production.compuserve.com> Xref: biosci bionet.microbiology:5692 bionet.molbio.ageing:2634 bionet.organisms.schistosoma:99 sci.bio.microbiology:3143 sci.environment:71177 We at Columbus Instruments developed RESPIROMETER that can be used to assess the oxygen consumption and carbon dioxide production starting from bacteria to animals and even in humans. The RESPIROMETER is being used by several researchers to determine the quality of meat through measuring the oxygen consumption and carbon dioxide production. If there is any bacterial contamination, it can be assessed from the results of oxygen consumption. For this reason, we belive that our RESPIROMETER can be used in detecting the contaminated beef and probably to diagnose whether the cow is infected with mad cow disease or not. If you need further information about our RESPIROMETER and its application, please send e-mail or fax to the following address. GHOSH Internet: 75144.2413@Compuserve.com Fax: 614-276-0529. From owner-ageing@net.bio.net Fri Apr 12 23:00:00 1996 Path: biosci!rutgers!gatech!newsfeed.internetmci.com!in1.uu.net!news.iij.ad.jp!fu.bekkoame.or.jp!suika!user From: akonishi@ppp.bekkoame.or.jp (Atsushi Konishi) Newsgroups: bionet.molbio.ageing Subject: Re: Telomerase & Aging Date: Sat, 13 Apr 1996 20:09:28 +0900 Organization: Bekkoame Internet Yokohama Lines: 32 Message-ID: References: NNTP-Posting-Host: yhm0134.bekkoame.or.jp In article , dashley@TENET.EDU (Don Ashley) wrote: >> Comment: The striking thing about telomerase expression which is thought to >> make cells immortal, is that it is NOT expressed by many cell types. It is >> clearly abundant in the reproductive cells which obviously allows them to make >> the species immortal, and abnormally in malignant cells likewise conferring >> replicative immortality to them, however, it is conspicuously absent in most >> somatic cells and tissues. It appears to be true that there is a low (<100X >> less activity) of telomerase in candidate hematapoietic stem cells, but the >> biology there is not clear and all the evidence suggests that telomeres are >> being lost with age in vivo in these cells and when the candidate cells are >> passaged in vitro as well. So clearly the telomerase that is there is not >> repairing telomere loss. The only normal cells that are known to have stable >> telomeres are the reproductive cells. (Keratinocyte stem cells may also have >> low levels, but again, they are not maintaining telomere length) Some recent paper about PBLs culturing with PHA says that telomerase activity increases more than 100 times in these cells. I re-examined this with My PBLs and their activity really increased as high as cancer cells. Are these results artifacts relating with the TRAP method? Or the data from telomerase assay in in vitro have nothing to do with the activity in in vivo with these cells? Does anyone over there have suggestions about this? Thanks. From owner-ageing@net.bio.net Fri Apr 12 23:00:00 1996 Path: biosci!rutgers!gatech!swrinde!elroy.jpl.nasa.gov!decwrl!waikato!news.express.co.nz!usenet From: stevense@iprolink.co.nz (Eric Stevens) Newsgroups: bionet.microbiology,bionet.molbio.ageing,bionet.organisms.schistosoma,sci.bio.microbiology,sci.environment Subject: Re: DEVICE FOR TESTING MAD COW Date: Sat, 13 Apr 1996 20:56:53 GMT Organization: Forensic Engineer Lines: 31 Message-ID: <31701228.2212159@news.iprolink.co.nz> References: <4kllag$3et$1@mhafc.production.compuserve.com> Reply-To: stevense@iprolink.co.nz NNTP-Posting-Host: stevense.iprolink.co.nz X-Newsreader: Forte Agent .99d/16.182 Xref: biosci bionet.microbiology:5720 bionet.molbio.ageing:2639 bionet.organisms.schistosoma:101 sci.bio.microbiology:3158 sci.environment:71327 On 12 Apr 1996 13:20:16 GMT, Jan Czekajewski Ph.D. <75144.2413@CompuServe.COM> wrote: >We at Columbus Instruments developed RESPIROMETER that can be >used to assess the oxygen consumption and carbon dioxide >production starting from bacteria to animals and even in humans. >The RESPIROMETER is being used by several researchers to >determine the quality of meat through measuring the oxygen >consumption and carbon dioxide production. If there is any >bacterial contamination, it can be assessed from the results of >oxygen consumption. For this reason, we belive that our >RESPIROMETER can be used in detecting the contaminated beef and >probably to diagnose whether the cow is infected with mad cow >disease or not. If you need further information about our >RESPIROMETER and its application, please send e-mail or fax to >the following address. But Mad Cow Disease (BSE) is not bacterial in origin, so what makes you think it will work? Eric Stevens Chaos is found in the greatest abundance wherever order is being sought. It always defeats order, because it is better organised. -: Ly Tin Wheedle From owner-ageing@net.bio.net Fri Apr 12 23:00:00 1996 Path: biosci!rutgers!gatech!newsfeed.internetmci.com!in2.uu.net!nntp.inet.fi!news.funet.fi!news.abo.fi!usenet From: krister Eriksson Newsgroups: bionet.microbiology,bionet.molbio.ageing,bionet.organisms.schistosoma,sci.bio.microbiology,sci.environment Subject: Re: DEVICE FOR TESTING MAD COW Date: Sun, 14 Apr 1996 00:46:52 -0700 Organization: Abo Akademi University Lines: 9 Message-ID: <3170AD6C.6492@aton.abo.fi> References: <4kllag$3et$1@mhafc.production.compuserve.com> NNTP-Posting-Host: ganglion.abo.fi Mime-Version: 1.0 Content-Type: text/plain; charset=iso-8859-1 Content-Transfer-Encoding: 8bit X-Mailer: Mozilla 2.0 (Win16; I) Xref: biosci bionet.microbiology:5719 bionet.molbio.ageing:2638 bionet.organisms.schistosoma:100 sci.bio.microbiology:3157 sci.environment:71326 Mad cow disease is not caused by bacteria. It is caused by an infectious protein, a prion, which almost certainly doesnīt consume any oxygen by itself. Just because this was posted in bionet.organisms.schistosoma, I would also like to point out that this disease isnīt caused by a flatworm either. Best regards, Krister From owner-ageing@net.bio.net Fri Apr 12 23:00:00 1996 Newsgroups: alt.cellular-phone-tech,alt.cellular.oki.900,bionet.metabolic-reg,bionet.molbio.ageing,comp.theory.cell-automata Path: biosci!agate!howland.reston.ans.net!newsfeed.internetmci.com!in2.uu.net!news.skyweb.net!not-for-mail From: pc11 Subject: Ericsson GH337 Message-ID: <317010F5.658D@cybergate.ibm.ch> Date: Sat, 13 Apr 1996 13:39:17 -0700 X-Mailer: Mozilla 2.0 (Win16; I) MIME-Version: 1.0 Content-Type: text/plain; charset=us-ascii Content-Transfer-Encoding: 7bit Lines: 11 Xref: biosci bionet.metabolic-reg:715 bionet.molbio.ageing:2637 comp.theory.cell-automata:2844 Please inform me about all the secret/possible codes, that this cellular have. My Email-Adress: chibmycq@ibmmail.com Thanks for all information best regards Francesco -- From owner-ageing@net.bio.net Sat Apr 13 23:00:00 1996 Path: biosci!agate!newsxfer2.itd.umich.edu!tank.news.pipex.net!pipex!dispatch.news.demon.net!demon!mail2news.demon.co.uk!longevb.demon.co.uk From: John de Rivaz Newsgroups: bionet.molbio.ageing Subject: Re: DEVICE FOR TESTING MAD COW Date: Sun, 14 Apr 1996 13:46:07 +0100 Organization: Myorganisation Lines: 39 Message-ID: <490353835wnr@longevb.demon.co.uk> References: <4kllag$3et$1@mhafc.production.compuserve.com> Reply-To: John@longevb.demon.co.uk X-NNTP-Posting-Host: longevb.demon.co.uk X-Newsreader: Newswin Alpha 0.9.1 X-Mail2News-Path: disperse.demon.co.uk!post.demon.co.uk!longevb.demon.co.uk In article: <4kllag$3et$1@mhafc.production.compuserve.com> Jan Czekajewski Ph.D. <75144.2413@CompuServe.COM> writes: > > We at Columbus Instruments developed RESPIROMETER that can be > used to assess the oxygen consumption and carbon dioxide > production starting from bacteria to animals and even in humans. > The RESPIROMETER is being used by several researchers to > determine the quality of meat through measuring the oxygen > consumption and carbon dioxide production. If there is any > bacterial contamination, it can be assessed from the results of ^^^^^^^^^^^ BSE is a prion disease, not a bacterial disease. > oxygen consumption. For this reason, we belive that our > RESPIROMETER can be used in detecting the contaminated beef and > probably to diagnose whether the cow is infected with mad cow > disease or not. If you need further information about our > RESPIROMETER and its application, please send e-mail or fax to > the following address. > > GHOSH > Internet: 75144.2413@Compuserve.com > Fax: 614-276-0529. > > -- Sincerely, **************************************** * Publisher of Longevity Report * John de Rivaz * Fractal Report * * details on request * **************************************** In the information age, sharing can increase world wealth enormously, because giving information does not decrease your information. http://ourworld.compuserve.com/homepages/JohndeR Fast loading, very few slow pictures From owner-ageing@net.bio.net Sat Apr 13 23:00:00 1996 Path: biosci!geron.com!mwest From: mwest@geron.com ("Mike West") Newsgroups: bionet.molbio.ageing Subject: FWD>RE>Telomerase & Aging Date: 14 Apr 1996 16:52:41 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 72 Sender: daemon@net.bio.net Distribution: world Message-ID: NNTP-Posting-Host: net.bio.net Mail*Link( SMTP FWD>RE>Telomerase & Aging Dear Atsushi, It would be helpful to know how you quantitated telomerase activity, was it by serial dilution, and what tumor cell line did you compare it to? Did you do a time course on the effect of PMA, what other cytokines were added (IL-2)? There is not yet a lot of data on telomeres and telomerase in cultured lymphocytes but the history of research in the field suggests that they lose telomeric DNA with age and have a finite replicative lifespan in vitro and are clearly losing telomeres in vivo. mwest@geron.com -------------------------------------- Date: 4/14/96 3:04 PM From: Atsushi Konishi In article , dashley@TENET.EDU (Don Ashley) wrote: >> Comment: The striking thing about telomerase expression which is thought to >> make cells immortal, is that it is NOT expressed by many cell types. It is >> clearly abundant in the reproductive cells which obviously allows them to make >> the species immortal, and abnormally in malignant cells likewise conferring >> replicative immortality to them, however, it is conspicuously absent in most >> somatic cells and tissues. It appears to be true that there is a low (<100X >> less activity) of telomerase in candidate hematapoietic stem cells, but the >> biology there is not clear and all the evidence suggests that telomeres are >> being lost with age in vivo in these cells and when the candidate cells are >> passaged in vitro as well. So clearly the telomerase that is there is not >> repairing telomere loss. The only normal cells that are known to have stable >> telomeres are the reproductive cells. (Keratinocyte stem cells may also have >> low levels, but again, they are not maintaining telomere length) Some recent paper about PBLs culturing with PHA says that telomerase activity increases more than 100 times in these cells. I re-examined this with My PBLs and their activity really increased as high as cancer cells. Are these results artifacts relating with the TRAP method? Or the data from telomerase assay in in vitro have nothing to do with the activity in in vivo with these cells? Does anyone over there have suggestions about this? Thanks. ------------------ RFC822 Header Follows ------------------ Received: by geron.com with SMTP;14 Apr 1996 14:48:52 -0700 Received: (from daemon@localhost) by net.bio.net (8.6.12/8.6.6) id EAA05072; Sat, 13 Apr 1996 04:27:02 -0700 Received: (from news@localhost) by net.bio.net (8.6.12/8.6.6) id EAA05028; Sat, 13 Apr 1996 04:26:56 -0700 To: ageing@net.bio.net From: akonishi@soda3.bekkoame.or.jp (Atsushi Konishi) Subject: Re: Telomerase & Aging Date: Sat, 13 Apr 1996 20:09:28 +0900 Message-ID: NNTP-Posting-Host: yhm0134.bekkoame.or.jp From owner-ageing@net.bio.net Sun Apr 14 23:00:00 1996 Path: biosci!TENET.EDU!dashley From: dashley@TENET.EDU (Don Ashley) Newsgroups: bionet.molbio.ageing Subject: Re: Cure AGE and AIDS Date: 14 Apr 1996 20:08:56 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 56 Sender: daemon@net.bio.net Distribution: world Message-ID: References: <199604111232.HAA02833@wubios.wustl.edu> NNTP-Posting-Host: net.bio.net Appropriate Humor Follows: On Thu, 11 Apr 1996, J. Philip Miller wrote: > dashley@tenet.edu (Don Ashley) writes: > > > > This sounds like AIDS. Curing AIDS and AGE have common objectives. > > AIDS gets more publicity and support from the media, however, as well as > > from the general public. Why is that? Why is there so much more hype > > about AIDS than AGE? AIDS just works a few years quicker. > > > Ah yes, I can see it now! we have a new public health problem - please do not > share body fluids with anyone with AGE - you might AGE yourself! Let us not > let any folks with AGE give blood -- if you receive such blood you might AGE > yourself! Thanks for the humor. It's really good and I think I'll use it in my talks. > > There are lots of lobbying groups in the US who push for funds for AGE > research now, some say they are even more effective than the AIDS folks, but > it wouldn't hurt to have more! If you know of any groups lobbying for AGE research, please let us know. AGE research would be to STOP the AGEING process; that is the process that causes our eyes to develop presbyopia and our skin to become more brittle. There are hundreds of groups that promote vitamins and longevity products to extend life a few years, but that is not the same as stopping aging. Curing the Old Age Disease Society is one group that exists to generate funding for research to stop the aging process. Please list others. Don Ashley J. Philip Miller, Professor, Division of Biostatistics, Box 8067 > Washington University Medical School, St. Louis MO 63110 > phil@wubios.WUstl.edu - (314) 362-3617 [362-2693(FAX)] > http://www.biostat.wustl.edu/~phil Kcomposer, only the message part of your mail is searched, and the cursor> Kis put on the first occurrence appearing after the location of the cursor. KThe search will wrap to the beginning of the message when it no longer Kfinds matches in the remainder of the message. K KTo search for the same st From owner-ageing@net.bio.net Sun Apr 14 23:00:00 1996 Path: biosci!TENET.EDU!dashley From: dashley@TENET.EDU (Don Ashley) Newsgroups: bionet.molbio.ageing Subject: Re: Telomerase & Aging Date: 14 Apr 1996 20:18:07 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 119 Sender: daemon@net.bio.net Distribution: world Message-ID: References: <316d7054.19621352@news.alt.net> NNTP-Posting-Host: net.bio.net Mike West founded Geron. 1987 <$100,000. 1996 >$70 million. On Thu, 11 Apr 1996, Jean-Pierre Issa wrote: > mwest@geron.com ("Mike West") wrote: > > > Subject: Time: 1:22 PM > > OFFICE MEMO Telomerase & Aging Date: 4/10/96 > > What office? :) If you don't mind me asking, do you work at Geron ? > > > > >In response to Dr. Issa's recent concerns about the telomere-aging connection > >I offer the following thoughts: > > No need to be formal: This is Usenet. Call me Jean-Pierre. > > >Comment: The striking thing about telomerase expression which is thought to > >make cells immortal, is that it is NOT expressed by many cell types. It is > >clearly abundant in the reproductive cells which obviously allows them to make > >the species immortal, and abnormally in malignant cells likewise conferring > >replicative immortality to them, however, it is conspicuously absent in most > >somatic cells and tissues. It appears to be true that there is a low (<100X > >less activity) of telomerase in candidate hematapoietic stem cells, but the > >biology there is not clear and all the evidence suggests that telomeres are > >being lost with age in vivo in these cells and when the candidate cells are > >passaged in vitro as well. So clearly the telomerase that is there is not > >repairing telomere loss. The only normal cells that are known to have stable > >telomeres are the reproductive cells. (Keratinocyte stem cells may also have > >low levels, but again, they are not maintaining telomere length) > > I do not have the paper in front of me, but I thought that peripheral > blood lymphocytes had about 10% of the telomerase activity seen in > some tumors. Also, I heard that stem cells from several different > organs have easily detectable telomerase activity. (Certainly, all > these cells have abundant telomere RNA as recently shown by Greider et > al. and others). > Stem cells, to my knowledge, cannot be passaged in-vitro (the > committed progeny quickly takes over the cultures). Thus, I am not > sure that stem cells still lose telomere length with age (correct me > if I am wrong...). > Still, why do aging tissues lose telomere length if stem cells express > telomerase ? Obviously, I don't know. Since 'committed' cells lose > telomerase activity, subsequent generations derived from these cells > will have shorter telomeres.Is it possible then that the loss of > telomere length in aging tissues reflects a changing ratio of stem > cells-early progenitors to late progenitors-differentiated cells ? > have I confused everybody ? > > (snip) > >Comment: This isn't really true. First, few would suggest that all of the > >cells in a given tissue would need to reach critical telomere length and the > >Hayflick limit for pathological consequences too occur. In the immune system, > >for example, perhaps only <10% of lymphocytes reaching senescence could impair > >a robust response to a pathogen and lead to a fatal infection. Similar logic > >would apply to other tissues. > > Yes and no... see my other post in this thread. > > > In the case of the immune system, lymphocytes > >are observed to reach the Hayflick limit at about 5-7 kbp terminal restriction > >fragment length which is interpreted as a "critical length" where perhaps one > >or more telomeres actually have lost repeats and trigger a cell cycle > >checkpoint arrest. If you look at the peripheral blood lymphocytes of aging > >people, you see the TRF length drops to about 5 kbp (the Hayflick limit) in > >centenarians (Am. J. Hum. Genetics 52: 661). Similar results have been > >reported for vascular intima, Hematapoietic stem cells (PNAS 91: 9857) etc. > > Please don't take my next remarks in a negative way: They are solely > for discussion purposes - I do believe telomeres are important ! > Nevertheless, the length of telomeres in peripheral blood lymphocytes > is not directly relevant to aging: These cells, for the most part, do > not divide... It may be relevant to gene expression changes and/or > genetic instability, but that remains to be demonstrated. > As mentioned above, what is critical to in vivo senescence / loss of > replicative ability is telomere length in stem cells. the PNAS paper > you reference is great. Nonetheless, to my knowledge, most stem cell > biologists believe that the 'true' stem cell is not necessarily the > CD34+ CD38lo fraction they studied. Primitive hematopoietic cells yes, > stem cells, probably not. Furthermore, as mentioned above, the 'stem > cell' is thought to be an essentially dormant cell. In culture, it > quickly is taken over by committed cells. Before you ask, I believe > the 'true' stem cell is this very rare cell that is required for > regenerating a lethally irradiated bone marrow, and that is (perhaps) > immortal. > the PNAS paper, however makes several important points relevant to > this discussion: In the same individual, telomere length is greater in > primitive hematopoietic cells than in differentiated cells. It is > therefore probably even greater in the 'true' stem cell... See above > for implications of this finding. Furthermore, in the paper, there > seems to be very little difference in telomere length between the bone > marrow of a 19 yr old, and the bone marrow of a 59 yr old... this begs > the question: is telomere length simply a reflection of differentiated > status rather than age ? (again, see above). > > (Snip) > > But, to argue against the telomere > >hypothesis for mammalian cells based on the fact that paramecia clonal > >senescence in the absence of conjugation is probably a stretch, don't you > >think? > > Absolutely. > Still, as I understand it, the relation between telomere length and > age is also confusing in rodents (am I wrong ?). Doesn't this trouble > you ? Anyone knows of a telomere length / aging connection in > primates? > > (Snip) > >But I assure you, much research into telomere length and aging is > >going on ! > >>Comment: A lot, especially in the telomerase-cancer connection. > > More research is good ! But, let's not get started on the > telomerase-cancer connection ! :) > > Thank you for a good discussion. > Jean-Pierre Issa > > From owner-ageing@net.bio.net Sun Apr 14 23:00:00 1996 Path: biosci!TENET.EDU!dashley From: dashley@TENET.EDU (Don Ashley) Newsgroups: bionet.molbio.ageing Subject: FWD>RE>Telomerase & Aging (fwd) Date: 14 Apr 1996 20:31:34 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 152 Sender: daemon@net.bio.net Distribution: world Message-ID: NNTP-Posting-Host: net.bio.net EMBO J Paper: ---------- Forwarded message ---------- Date: 11 Apr 1996 14:56:37 -0700 From: Mike West To: ageing@net.bio.net Subject: FWD>RE>Telomerase & Aging Mail*Link( SMTP FWD>RE>Telomerase & Aging Article is titled "Experimental elongation of telomeres extends the lifespan of immortal X normal cell hybrids" and appeared in the March 15th 1996 issue of EMBO J. vol. 15 (sorry I don't have page numbers). First author is Wright, W.E. -------------------------------------- Date: 4/11/96 7:01 AM From: Don Ashley This is a request for a source and summary of the EMBO J paper cited below showing the relationship of telomere length to replicative lifespan of cells. Thanks....Don Ashley, Houston On 10 Apr 1996, Mike West wrote: > Subject: Time: 1:22 PM > OFFICE MEMO Telomerase & Aging Date: 4/10/96 > > In response to Dr. Issa's recent concerns about the telomere-aging connection > I offer the following thoughts: > > His comments were: > > There are many more good labs studying the telomere/aging connection > than you imply. Unfortunately, there are many holes in the > (fascinating) speculation that telomere loss 'causes' aging. Some that > come to mind: > 1- Many normal cells (specially stem cells) express telomerase and > thus can repair/replace any significant telomere loss. > > Comment: The striking thing about telomerase expression which is thought to > make cells immortal, is that it is NOT expressed by many cell types. It is > clearly abundant in the reproductive cells which obviously allows them to make > the species immortal, and abnormally in malignant cells likewise conferring > replicative immortality to them, however, it is conspicuously absent in most > somatic cells and tissues. It appears to be true that there is a low (<100X > less activity) of telomerase in candidate hematapoietic stem cells, but the > biology there is not clear and all the evidence suggests that telomeres are > being lost with age in vivo in these cells and when the candidate cells are > passaged in vitro as well. So clearly the telomerase that is there is not > repairing telomere loss. The only normal cells that are known to have stable > telomeres are the reproductive cells. (Keratinocyte stem cells may also have > low levels, but again, they are not maintaining telomere length) > > 2- Cells from elderly individuals have not yet reached a 'critical' > telomere shortening (which happens if you culture these cells to > senescence. > > Comment: This isn't really true. First, few would suggest that all of the > cells in a given tissue would need to reach critical telomere length and the > Hayflick limit for pathological consequences too occur. In the immune system, > for example, perhaps only <10% of lymphocytes reaching senescence could impair > a robust response to a pathogen and lead to a fatal infection. Similar logic > would apply to other tissues. In the case of the immune system, lymphocytes > are observed to reach the Hayflick limit at about 5-7 kbp terminal restriction > fragment length which is interpreted as a "critical length" where perhaps one > or more telomeres actually have lost repeats and trigger a cell cycle > checkpoint arrest. If you look at the peripheral blood lymphocytes of aging > people, you see the TRF length drops to about 5 kbp (the Hayflick limit) in > centenarians (Am. J. Hum. Genetics 52: 661). Similar results have been > reported for vascular intima, Hematapoietic stem cells (PNAS 91: 9857) etc. > > 3- Dr. Blackburn (one of the telomere pioneers) has shown that in > Tetrahymena (I think, but I may be wrong), telomeres shorten until > middle-age, THEN they start elongating again! At the end of these > organisms' life span, their telomeres are nearly the same length as > when they are born. (PNAS, 1994). > > Actually paramecia. Yes, maybe the senescence you see in paramecia is caused > by another mechanism (though some argue that Dr. Blackburn's data actually > support a role for telomere loss in this peculiar type of senescence). It is > certainly true that telomere loss appears to play no role in the limited > budding capacity of maternal yeast. But, to argue against the telomere > hypothesis for mammalian cells based on the fact that paramecia clonal > senescence in the absence of conjugation is probably a stretch, don't you > think? > > Thus, the telomere loss - aging connection remains somewhat > speculative. It is possible that even a small degree of telomere > shortening causes significant changes in gene expression elsewhere in > the genome, thus linking it to aging, but I do not think this has been > firmly demonstrated yet. > > Comment: I think everyone would agree that the hypothesis is still "young" > but the amazing thing to me is the breadth of data pouring in to support it > (such as the recent EMBO J paper showing a direct causal connection e.g. lengthening > telomeres increases the replicative lifespan of cells) and the predictive > power of the theory. Please summarize and give source of the EMBO J paper.....Don > > But I assure you, much research into telomere length and aging is > going on ! > > Comment: A lot, especially in the telomerase-cancer connection. > > -MWest > > Regards, > Jean-Pierre Issa, MD > Johns Hopkins Oncology Center > > > ------------------ RFC822 Header Follows ------------------ Received: by geron.com with SMTP;11 Apr 1996 02:12:29 -0700 Received: from net.bio.net by mx2.smtp.psi.net (8.7.5/SMI-5.4-PSI) id EAA01298; Thu, 11 Apr 1996 04:58:00 -0400 (EDT) Received: (from daemon@localhost) by net.bio.net (8.6.12/8.6.6) id BAA14042; Thu, 11 Apr 1996 01:50:43 -0700 Received: (from news@localhost) by net.bio.net (8.6.12/8.6.6) id BAA14036; Thu, 11 Apr 1996 01:50:38 -0700 To: ageing@net.bio.net From: dashley@tenet.edu (Don Ashley) Subject: Re: Telomerase & Aging Date: 11 Apr 1996 01:50:19 -0700 Sender: daemon@net.bio.net Message-ID: NNTP-Posting-Host: net.bio.net From owner-ageing@net.bio.net Sun Apr 14 23:00:00 1996 Path: biosci!TENET.EDU!dashley From: dashley@TENET.EDU (Don Ashley) Newsgroups: bionet.molbio.ageing Subject: Re: Telomere questions (fwd) Date: 14 Apr 1996 20:38:30 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 147 Sender: daemon@net.bio.net Distribution: world Message-ID: NNTP-Posting-Host: net.bio.net ---------- Forwarded message ---------- Date: Fri, 12 Apr 1996 07:42:13 -0400 From: Dennis Fink To: Multiple recipients of list LONGEVITY Subject: Re: Telomere questions In a message dated 96-04-11 05:07:29 EDT, Don wrote: >Can you enlighten in lay terms? Thanks for forwarding the very interesting material Don. Until more research is done we just can't be sure how important being able lengthen the lives of certain cells (by lengthening the telomeres) will be to the overall aging process. I would think that this will be very useful in certain situations but whether or not it is the primary cause of aging remains to be shown, at least from what I have seen. Kevin asked: >Admittedly it is far too early to peg telomere shortening (loss? I don't >know the proper terminology here) as the cause of ageing, but from what >I read on the net there would seem to be a strong connection. Two >questions come to my mind. First, is there some material that a >person like myself (not a biology major) can read and understand on >the subject? Second, to date, has any method been found that >prevents or significantly slows down the rate of telomere shortening? >It seems to me that the latter might place you in a bit higher risk of >cancer than otherwise though. > This will be a significant problem for lengthening cell lifespan without increasing cancer risk. I'll include some material from my e-text which addresses these issues and gives three references for more info. There are even entire books on telomeres already but that is likely more than a non - biologist wants. >Recently I saw a TV interview in which some Ph.D. or other said that >many cells in the human body were effectlively immortal. Do these >cells (if this is true) achieve this via prevention of telomere >shortening, and if so (and this is the big question here) do these >kinds of cells show a greater tendency to go cancerous than other >types of cells? If not, what prevents this? > I'm not sure we have all these answers yet. The Scientific American work referenced below described many cells as having sufficient telomere length and replication rate that the telomeres do not seem to be important to aging as it occurs today, at least for many cells. Further, the cells that bear the brunt of aging (i.e., the brain cells) don't even divide. Some of the other familiar changes of aging are programmed genetically (eg., the loss of receptors from the erectile tissues, which are also made up of non-dividing cells). >All of this assumes that my questions are not so off base as to make >no sense at all... > Your questions are right on target Kevin! Out of context ASCII extracts (no italics, etc.) from my e-text, health70 (available at cost) ------------------------- Carol Orlock in The End of Aging (p. 99) notes the similarity in the number of cell divisions and lifespan in several animals. She cites the gradually increasing lifespans of the mouse, chicken, human and Galapagos tortoise, and the gradually increasing number of cell divisions of 14 to 28 (mouse), 15 to 35 (chicken), 50 to 60 (human) and 90 to 125 divisions for the long lived tortoise. Orlock, noting that by age seventy five, we loose about a third of the cells that we had at peak cell count, feels that it might be helpful to be able to extend the doubling time of certain vital cells. In the case of the rare condition known as progeria, which is essentially a disease of accelerated aging, Orlock states (p. 103) that cells divide only about twenty times, whereas they might normally double about 60 times. The decreased number of divisions appears to be due to shortened telomeres (discussed more below), segments on the ends of chromosomes which shorten with each cell division. There is more to aging than just telomere length though since it varies considerably among people of the same age, and some researchers say cells can usually divide more times than is required in a human life span (Scientific American, February 1996, p. 95). Genetics likely plays a significant role in telomere length and aging, but, as discussed below, is probably not the most important factor. Robert Erdmann, Ph.D., (The Amino Acid Revolution, p. 186) says progeria involves the inability to produce the two enzymes that help keep free radicals in check: superoxide dismutase (SOD) and glutathione peroxidase (GTP). Orlock also discusses (p. 101) the cell suicide schedule (research done in animals that undergo metamorphosis) and the rpr gene which has been dubbed the "reaper" gene because it appears to be responsible for cell death, and the "savior" gene that keeps the "reaper" gene suppressed and also plays a role in helping the cell produce antioxidants. When the savior gene is turned off in mice they die in infancy or appear to be subjected to accelerated aging, like the progeria just mentioned in the previous paragraph. --------------------------- --------------------------- Cellular aging Dr. Hayflick is well known for his often cited work that changed the thinking of gerontologists in the 1960s when he convinced skeptics that his research was valid that showed that normal cells in tissue culture were not immortal, but divided only a certain number of times (50 divisions in the cells he used). This work and work by others indicates the presence of an internal cellular clock and some work has recently identified the ends of the chromosomes, called telomeres, as one possible clock mechanism. Cancer cells which are immortal have an enzyme called telomerase which prevents the ends of the chromosomes from gradually shortening with each cell division which eventually is thought to stop cell replication. Dr. Hayflick however does not believe that aging or death is due to cells not dividing (p. 133). Serial transplants where cells are repeatedly transplanted from one animal to a younger animal have shown that cell lifespan can be extended by keeping it in a "younger environment" so there is some evidence that factors external to the cells affect their lifespan as well. Cells from progeria and Werner syndrome patients "age faster than do similar cells taken from age - matched controls," according to Dr. Hayflick (p. 108). --------------------------- -------------------------- Robin Holliday in Understanding Ageing, says "It is probable that whitening of the hair is due to the age - related loss of pigment - forming cells (melanocytes)." This may be an example of the limited proliferation ability of some somatic cells, which may mean that some of the "immortalizing" telomerase enzyme that is present in virtually every type of cancer cell might be needed in these cells to lengthen the telomeres (the ends of the chromosome). The enzyme is believed responsible for the immortalization of cancer cells by preventing the shortening of the telomeres which in normal cells eventually leads to lack of cell division. Too much of the enzyme seems to cause immortalization (and often cancer) but if none is present, the cells eventually loose the chromosome telomeres and the capability to divide. Genes close to the end of the chromosome are even lost after the telomeres are lost so if these are important genes, the capability of the cell to function normally, gradually declines. It has been found that normal fibroblasts can be transformed by certain viruses to abnormal cells, like neoplastic cells (cells that form new tissue). Yet these cells are not immortalized and they are not tumorigenic. Holliday points out that this "suggests that a barrier does exist that prevents the emergence of cancer cells" (p. 81). Human B lymphocytes on the other hand can be readily immortalized by the Epstein - Barr virus, but these cells appear to remain normal. Research in this area is of course intensive since cancer is linked this area of research. --------------------------------- I hope that helps! Sincerely, Dennis Fink From owner-ageing@net.bio.net Sun Apr 14 23:00:00 1996 Path: biosci!TENET.EDU!dashley From: dashley@TENET.EDU (Don Ashley) Newsgroups: bionet.molbio.ageing Subject: Re: New aging insights in Science? Date: 14 Apr 1996 20:41:37 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 17 Sender: daemon@net.bio.net Distribution: world Message-ID: References: NNTP-Posting-Host: net.bio.net The same story came out in Associated Press with no sources of referrral. On Fri, 12 Apr 1996 yeger@m1.sprynet.com wrote: > > The front of the Wall Street Journal had a blurb to the effect that > researchers discovered the gene that causes Werner's syndrome, a disease > marked by premature ageing, that it boosts insights into normal aging, and > that the results are published in Science. I got the April 5 issue today and > didn't find anything. Anyone know anything about this? > > Thanks, > Jim > > > > From owner-ageing@net.bio.net Mon Apr 15 23:00:00 1996 Path: biosci!newshost.lanl.gov!ncar!gatech!newsfeed.internetmci.com!howland.reston.ans.net!news-e2a.gnn.com!newstf01.news.aol.com!newsbf02.news.aol.com!not-for-mail From: douglooker@aol.com (Douglooker) Newsgroups: bionet.microbiology,bionet.molbio.ageing,bionet.organisms.schistosoma,sci.bio.microbiology,sci.environment Subject: Re: DEVICE FOR TESTING MAD COW Date: 16 Apr 1996 16:42:31 -0400 Organization: America Online, Inc. (1-800-827-6364) Lines: 1 Sender: root@newsbf02.news.aol.com Message-ID: <4l10nn$973@newsbf02.news.aol.com> References: <3170AD6C.6492@aton.abo.fi> Reply-To: douglooker@aol.com (Douglooker) NNTP-Posting-Host: newsbf02.mail.aol.com Xref: biosci bionet.microbiology:5749 bionet.molbio.ageing:2652 bionet.organisms.schistosoma:102 sci.bio.microbiology:3178 sci.environment:71604 Can I buy a used car from this guy. Or maybe a bridge From owner-ageing@net.bio.net Mon Apr 15 23:00:00 1996 Path: biosci!daresbury!not-for-mail From: Newsgroups: bionet.molbio.ageing Subject: Special project request Date: 16 Apr 1996 05:16:43 +0100 Lines: 46 Sender: lpddist@mserv1.dl.ac.uk Distribution: bionet Message-ID: <4kv6vb$34c@mserv1.dl.ac.uk> Original-To: ADMIN-L@albanydh2, ADMARA@albanydh2, AGEING@dl.ac.uk, AGRIS-L@irmfao01, AHL@gwuvm, AIDS@uscvm, AIDS-STAT@wubios.wustl.edu Please forgive this impersonal, and ultimately non-participatory request from your list. I am looking for people willing to participate in an art project and thought that people on the Internet of similar, if only tangential interests might help me. This summer I plan to stand on Chicago street corners and ask people if they will let me take a photo of their smallpox vaccination scar. As you may know, almost twenty years ago the World Health Organization officially declared smallpox as an eradicated disease. That leaves only the scars of vaccination as testament (aside from apparently two vials of the Variola virus in safekeeping - one in Russia and the other at the CDC, and 500,000 doses of the vaccine kept by WHO). And, as we are all mortal, we that carry the scar will, after a time, vanish as well. Perhaps contemporary health issues like AIDS will come to mind as a similar, though less swift, disaster as the smallpox epidemics of one, two and three hundreds years ago. Indeed, I am mindful of the role smallpox played in the annihilation of much of the indigenous populations in the western hemisphere. And now, with increased incidents of TB and polio, along with ebola and a host (no pun intended) of other bugs coming out of the woods and onto the scene, I cannot help wonder if smallpox will somehow rear its ugly pustules again. There are other issues that the smallpox scar plays into in the art world, such as ritual scarification and tattoos, but I digress from my request. I am asking people on the Internet to provide me with close-up photos (black & white or color, any size film, except slides) of their own, and/or others' smallpox vaccination scars. Photos (date of birth and names of participants are optional).should be sent to the gallery that represents me: Beret International, 1550 N. Milwaukee Ave., Chicago, IL 60622, USA. My goal is to fill entire walls with these photos in the Fall of 1996. They will be a strong testament to the living and remind us of those we have lost to diseases - not to mention what medicine and society at large can do when it puts its collective mind to it. As I ideally would like worldwide participation, I would also ask that my request be forwarded to other lists that you participate on. Thank you for any aspect of my request you decide to do. Sincerely, Patrick Collier PtCPatrick@AOL.com From owner-ageing@net.bio.net Mon Apr 15 23:00:00 1996 Path: biosci!agate!spool.mu.edu!usenet.eel.ufl.edu!newsfeed.internetmci.com!howland.reston.ans.net!psinntp!psinntp!psinntp!psinntp!usenet From: yo_doc@usa.pipeline.com(Richard A. Lockshin) Newsgroups: bionet.molbio.ageing Subject: NYC Cell Death Club Meeting Date: 15 Apr 1996 23:07:16 GMT Organization: Pipeline USA Lines: 49 Message-ID: <4kukr4$53j@news1.h1.usa.pipeline.com> NNTP-Posting-Host: 38.8.120.14 X-PipeUser: yo_doc X-PipeHub: usa.pipeline.com X-PipeGCOS: (Richard A. Lockshin) X-Newsreader: Pipeline v3.5.0 NYC Area Cell Death Club Next meeting: Wednesday, May 1, 1996 6:00-6:30 PM Pizza 6:30-8:00 PM Talks and discussion Rockefeller University, 1230 York Ave., Weiss Research Bldg Room 301 Free Parking after 5PM at 66th St. & York Ave (Please carpool as parking space is limited) Speakers: 1. Dr. Douglas Miller, Merck Research Laboratory THE ROLE OF THE ICE FAMILY OF CYSTEINE PROTEASES IN INFLAMMATION AND APOPTOSIS 2. Dr. Eileen White, CABM Rutgers University REGULATION OF P53-DEPENDENT APOPTOSIS BY MEMBERS OF THE BCL-2 FAMILY To help plan for pizza call lab of Dr. Zahra Zakeri, 718: 997-3429 and let them know the number coming for pizza, talk, and if you need parking. Please RSVP by Tues, April 30, 1996. Otherwise email to me here or to lockshin@sjumusic.stjohns.edu IF YOU WANT TO RECEIVE DIRECT EMAIL NOTIFICATION, PLEASE SEND REPLY, FILLING IN THE FOLLOWING BLANKS (NO SPACES AFTER COLON) FIRST NAME: LAST NAME: EMAIL ADDRESS: ADDRESSLINE1: ADDRESSLINE2: INSTITUTION: STREETADDRESS: CITY: STATE: ZIP: INTEREST: Organizers: Zahra Zakeri, Fax 718: 997-3445 Phone 718: 997-3417 Raymond Birge: Fax 212 327-7943; Phone 212: 327-7412 Richard Lockshin Fax 718: 990-1854 Phone 718: 380-8543 Sponsored by: Oncor Appligene Cell Death and Differentiation -- Richard A. Lockshin -- Richard A. Lockshin From owner-ageing@net.bio.net Mon Apr 15 23:00:00 1996 Path: biosci!daresbury!nntp-trd.UNINETT.no!nntp.uio.no!news.cais.net!newsfeed.internetmci.com!usenet.eel.ufl.edu!news.alt.net!newspost1.alt.net!usenet From: jpissa@welchlink.welch.jhu.edu (Jean-Pierre Issa) Newsgroups: bionet.molbio.ageing Subject: Re: telomeres and aging Date: Tue, 16 Apr 1996 14:27:50 GMT Organization: j Lines: 53 Message-ID: <3173ae56.68431606@news.alt.net> References: Reply-To: jpissa@welchlink.welch.jhu.edu X-Newsreader: Forte Agent .99d/16.182 Mike, You make many excellent points. I agree that the age-related emergence of an 'abnormal' population of cells that secretes proteases etc... could be a major factor in in-vivo aging. I was not aware, however, that cells that which reached replicative senescence could display such gain of function - I always thought of these cells as essentially quiescent. I stand corrected (and educated...). You have to admit, though, that data is lacking to link telomere shortening with such gene 'activation'. I also do not believe that the issue of telomere shortening in any stem cell (lung, colon, hematopoietic...) has been resolved. This is obviously the subject of further research rather than further discussion... Finally, I would like to hear your thoughts on the implications of telomerase activity in mouse cells: Mice still senesce in-vivo and die... I am not sure that the cancer incidence in non-inbred mice is much higher than that seen in humans... Doesn't this argue against the telomere loss/aging connection and the telomerase/cancer connection ? Jean-Pierre Issa mwest@geron.com ("Mike West") wrote: > >I agree that the age-dependent loss of myocardial function probably reflects >muscle loss by vascular insufficiency or loss from other causes than cell >senescence since the myocardium is postmitotic in the adult and has no stem >cells. I doubt that anyone would suggest that all pathology is directly >linked to cell senescence. But one could argue that loss of myocardium >through ischemia is indirectly caused by atherosclerosis, which may in turn be >(in part) caused by the senescence of the endothelium. This is actually an >interesting possibility since telomeres are observed to shorten with age in >the intima, and particularly in vessels where atherosclerosis is observed. >Also, the role of endothelial injury in the early stages of athero is now well >accepted, and accelerated cell turnover of endothelial cells is seen in