From owner-ageing@net.bio.net Sat Apr 01 23:00:00 1995 Path: biosci!agate!dog.ee.lbl.gov!news.cs.utah.edu!news.cc.utah.edu!corona!patrick From: Patrick O'Neil Newsgroups: bionet.molbio.ageing Subject: Re: Must an AGING PROCESS be universal? Date: Sat, 1 Apr 1995 21:36:44 -0700 Organization: University Of Utah Computer Center Lines: 44 Message-ID: References: <3lgf2r$dui@mserv1.dl.ac.uk> NNTP-Posting-Host: corona.med.utah.edu Mime-Version: 1.0 Content-Type: TEXT/PLAIN; charset=US-ASCII In-Reply-To: On Sat, 1 Apr 1995, Oliver Bogler wrote: > I agree with Andy - some cells in a lineage must be immortal. This line of > thought tends to blur the distinction between organisms and species (for > me at least). If you consider the DNA in you, it is a copy of the DNA that > was in the very first human, albeit not an accurate one. It has been > carried from that human to you by an unbroken chain of cells. Of course > most of those cells are dead now, but the chain is unbroken, and so the Hardly a satisfactory treatment of ageing. By this thought process, humans (and everything else alive today) are "immortal" in that they are all copies, albeit imperfect, of predecessors...in an unbroken chain. By this same token, we are ALL the imperfect copy of the first true living organism which, by extension, is "immortal" with an age of some 4.5 billion years and counting. Hell, why all the fuss about any kind of life extension? The DNA and proteins that first made me no longer exist, as they were the precise strands of DNA and extant proteins within the zygote that led to me. Those original cells and their contents have long ceased to exist leaving me with many imperfect copies of that first progenitor. I have cells dying all the time, some of which are replaced, many that are not, none of which are immortal. Even stem cells cannot be said to be, in and of themselves, immortal (I really hate that word...NOTHING can be immortal because even matter has a finite existence). The stem cells (plural) that lead to the blood presently coursing through my veins need by no means to still exist tomorrow. They have divided into other stem cell copies, some of which die...perhaps including those that carried the original parental DNA. These cells have led to differentiated cells, which die even as some of the stem cells die. What PARTICULAR cell in anyone's body lives indefinitely? Tag any stem cell, perhaps with a fluorescent tag or radioactive P, C, or H and then tell us whether THAT PARTICULAR cell remains for 70 or 80 years, or even a significant fraction thereof. I do not believe you would ever discover such a cell. Stem cells do not have to be immortal, only constantly replicated. The progenitors to generation A stem cells need not remain to be the progenitors of generation F. The original, parental DNA from any stem cell gets diluted out after only a handful of cellular generations, and can even be entirely replaced by mismatch repair, excision repair, recombination, and cellular death. The strands aren't the energizer bunny. Patrick From owner-ageing@net.bio.net Sat Apr 01 23:00:00 1995 Path: biosci!agate!newsxfer.itd.umich.edu!zip.eecs.umich.edu!caen!uwm.edu!fnnews.fnal.gov!nntp-server.caltech.edu!NewsWatcher!user From: grovesa@starbase1.caltech.edu (Andrew K. Groves) Newsgroups: bionet.molbio.ageing Subject: Re: Must an AGING PROCESS be universal? Date: Sun, 02 Apr 1995 00:06:30 -0800 Organization: California Institute of Technology Lines: 86 Message-ID: References: <3lgf2r$dui@mserv1.dl.ac.uk> NNTP-Posting-Host: mac168.bio.caltech.edu In article , Patrick O'Neil wrote: > The DNA and proteins that first made me no longer exist, as they were > the precise strands of DNA and extant proteins within the zygote that led > to me. Those original cells and their contents have long ceased to exist > leaving me with many imperfect copies of that first progenitor. I have > cells dying all the time, some of which are replaced, many that are not, > none of which are immortal. Even stem cells cannot be said to be, in and > of themselves, immortal (I really hate that word...NOTHING can be > immortal because even matter has a finite existence). The stem cells > (plural) that lead to the blood presently coursing through my veins need > by no means to still exist tomorrow. They have divided into other stem > cell copies, some of which die...perhaps including those that carried the > original parental DNA. These cells have led to differentiated cells, > which die even as some of the stem cells die. What PARTICULAR cell in > anyone's body lives indefinitely? Tag any stem cell, perhaps with a > fluorescent tag or radioactive P, C, or H and then tell us whether THAT > PARTICULAR cell remains for 70 or 80 years, or even a significant > fraction thereof. I do not believe you would ever discover such a cell. > Stem cells do not have to be immortal, only constantly replicated. The > progenitors to generation A stem cells need not remain to be the > progenitors of generation F. The original, parental DNA from any stem > cell gets diluted out after only a handful of cellular generations, and > can even be entirely replaced by mismatch repair, excision repair, > recombination, and cellular death. The strands aren't the energizer bunny. > We are dealing with a problem of definition here. Dr. Bogler and myself are using a set of precise definitions (which I will outline below) that are used by biologists working on the problems of cell division. You are taking exception to Oliver's comments because you are using (and disliking) the word "immortal" in a different way to us. I'll illustrate what we are talking about by means of a set of simple experiments that have been performed time and again in labs all over the world.I apologise if this is all old news to you, but I feel we need to make clear our definitions if we are to avoid arguing at cross-purposes. If you take a population of embryonic rat fibroblasts (a loosely defined mesenchymal cell population obtained by dissociating an embryonic rat carcass) and grow them in a culture dish, you will notice that the cells divide and rapidly fill up the area on the dish. At this point, they will stop dividing. They are said to be QUIESCENT. If you dissociate the cells on the dish, and replate them at a lower density, the cells will start dividing again. You can repeat this process between four and six times (by which time each of your founder cells will have divided probably between 20 and 30 times). At this point, the cells once more stop dividing, and become noticeably flattened. They cannot now be induced to divide any more. They are said now to be SENESCENT. Senescent cells do not die - they just sit there and carry on metabolising but cannot divide any further. We would interpret this phenomenon by saying that the cells we isolated from the rat embryos have a finite limit to the number of divisions they can undergo. This will tend to be roughly the same number in every experiment you perform. It is possible to carry out manipulations whilst these cells are still dividing that will override their limit to cell division. This can be done by, for example, introducing certain oncogenes such as v-myc, or the SV40 large T antigen. The cells will now continue to divide in culture indefinitely and will not respect their normal limited number of divisions. We call these cells IMMORTAL, in that they can be propagated indefinitely in culture, and the oncogenes that cause these effects IMMORTALISING ONCOGENES. Note that this is a narrow but precise definition of the word immortal used by biologists. Immortal cells are not 'cancerous'. If you inject immortalised fibroblasts into anmals, they will not form tumours. In order to become tumourigenic, or what we refer to as TRANSFORMED, other cellular changes have to occur, or need to be artificially introduced by, for example transforming oncogenes, such as the activated ras oncogene. My point here is that biologists tend to define immortal cells NOT as cells that 'live forever', but as cells that have no intrinsic limit to the number of divisions they can undergo. This is in stark contrast to most normal cells, which appear to have a pre-programmed number of cell divisions. Stem cells do not appear have a limit to the number of divisions they can undergo. I hope this goes some way to clarifying what we mean. -- Andy Groves Division of Biology, 216-76 California Institute of Technology From owner-ageing@net.bio.net Sat Apr 01 23:00:00 1995 Path: biosci!galaxy.ucr.edu!library.ucla.edu!agate!tcsi.tcs.com!uunet!in1.uu.net!comp.vuw.ac.nz!waikato!auckland.ac.nz!kcbbs!planet!chambers!steve From: steve@chambers.ak.planet.co.nz (Steve Chambers) Newsgroups: bionet.molbio.ageing,sci.life-extension Subject: Re: Must an AGING PROCESS be universal? was Defining... Message-ID: Date: Sun, 2 Apr 95 15:13:43 +1200 Organization: PlaNet (Auckland New Zealand) Lines: 36 Xref: biosci bionet.molbio.ageing:1638 sci.life-extension:4552 In obogler@ucsd.edu (Oliver Bogler) writes: >The question is, I agree, to what extent external processes affect ageing. >In other words, can environmental differences or biochemical differences >that are inherent really change the way we age? This would offer avenues >of intervention. Exactly. The issue then becomes: On which processes do we focus to achieve the most effective intervention? This is why a reeaxination of what constitutes an aging process is necessary. By excluding from aging the myriad common life-limiting processes that aren't universal we may be throwing out the baby with the bath water. We may also be severely limiting our chances of success by assuming that a single process can explain mortality in the oldest old of any species. Much emphasis is placed on changes to "maximum lifespan" as a measure of the effectiveness of any intervention - but if no single process is to blame then it's likely that no _single_ intervention will change this maximum. It's possible that MULTIPLE known interventions could extend maximum lifespan. We could already have effective tools without knowing it. Steve -- ________________________ (I_lurk,_therefore_I_am!_\ ,,, Steve Chambers (o o) steve@chambers.ak.planet.co.nz ----------------------oOO--(_)--OOo----------------------------- (c) Steve Chambers 1995. All rights reserved ---------------------------------------------------------------- From owner-ageing@net.bio.net Sat Apr 01 23:00:00 1995 Path: biosci!agate!howland.reston.ans.net!cs.utexas.edu!uunet!in1.uu.net!comp.vuw.ac.nz!waikato!auckland.ac.nz!kcbbs!planet!chambers!steve From: steve@chambers.ak.planet.co.nz (Steve Chambers) Newsgroups: bionet.molbio.ageing Subject: Cellular senescence- is it aging? was Defining... Message-ID: <-EwfvAeABh107h@chambers.ak.planet.co.nz> Date: Sun, 2 Apr 95 15:55:43 +1200 Organization: PlaNet (Auckland New Zealand) Lines: 47 In grovesa@starbase1.caltech.edu (Andrew K. Groves) writes: >I think there is a confusion here between biological ageing and >pathological conditions which lower life span - between cellular and >organismal aging, if you will. If you place a population of human >fibroblasts in culture, they will divide for a certain number of times and >stop. They will not die, they'll just sit there. If you're skilful, you >can maintain such senescent cultures for months and even years. But the >point is that those cells have all stopped dividing after a seemingly >pre-programmed period of time. How could random wear and tear account for >such an impressive synchrony of withdrawal from the cell cycle? >I'm not suggesting that senscence has a single cause - indeed, the work of >Olivia Pereira-Smith would suggest that there are several mechanisms on >the basis of genetic complementation in somatic cell fusion experiments. >Your "100+" mechanisms of wera and tear may well explain why people die, >or get cancer or whatever, but they may not be able to account for the >reproducible obseravtion of cellular senescence. Andy There's a tendency for those of us who've spent most of our studies in cellular and molecular biology to think that the term senescence (and by implication aging) only applies to cells. It doesn't - and for most of the community the terms apply principally to whole organisms. The processes that dictate the "lifespan" of a cell or clone are but a small subset of those that should be examined when studying aging. Genetic control is plainly a major factor in cellular senescence but cellular senescence probably doesn't "explain why people die." There's a hackneyed quote in gerontology: "Nobody dies of old skin." You have to ask yourself a question: If current definitions of aging (including one that relies upon cellular senescence) don't "explain why people die" then how useful are they? Steve -- ________________________ (I_lurk,_therefore_I_am!_\ ,,, Steve Chambers (o o) steve@chambers.ak.planet.co.nz ----------------------oOO--(_)--OOo----------------------------- (c) Steve Chambers 1995. All rights reserved ---------------------------------------------------------------- From owner-ageing@net.bio.net Sat Apr 01 23:00:00 1995 Path: biosci!agate!howland.reston.ans.net!news.sprintlink.net!nwnexus!news.halcyon.com!flames!venezia From: venezia@zgi.com (Domenick Venezia) Newsgroups: bionet.molbio.ageing Subject: Re: Must an AGING PROCESS be universal? Date: 2 Apr 1995 16:41:15 GMT Organization: Northwest Nexus Inc. Lines: 34 Distribution: bionet Message-ID: <3lmk3b$o03@news.halcyon.com> References: <3ljpem$ldr@mserv1.dl.ac.uk> NNTP-Posting-Host: flames.zgi.com X-Newsreader: TIN [version 1.2 PL2] Andrew K. Groves (grovesa@starbase1.caltech.edu) wrote: > > I disagree, and cite my examples of stem cells in bone marrow, gut and > skin. These cells do not appear to have a limit on the number of times > that they can divide in the living animal. ... > ... There are dividing stem cells in the gut of 120 year old humans, > and there is no reason to think that they have a limit on division. > > I stress this by way of comparison to cells that have a "Hayflick" limit. > Some cells in an animal DO have a seemingly pre-programmed number of > divisions, and will eventually stop dividing. They won't necessarily die - > they will just be unable to divide. Stem cells in the gut, bone marrow and > skin do not behave like this, even though the differentiated progeny to > which they give rise do. Is senescence not a probabilistic process with a presumably gaussian distribution? Don't we lose individual stem cells one at a time? The stem cells left in a 120 year old are simply those few on the extreme right of the distribution. Couldn't this be the reason our skins get thinner, and our digestion gets poorer as we age? The number of stem cells regenerating these tissues is less, and the tissue regeneration is no longer as robust? So I think the Hayflick limit is active in human stem cells, and isn't that the whole implicit assumption of the telomere/telomerase work? That shortened telomeres lead to senescence of stem cells and that the result of that senescence is the Hayflick limit? If you have data that suggests that human stem cells in vivo are in fact immortal I'd like to have a look at it, because it would completely change the way myself and many others think about aging. Domenick Venezia ZymoGenetics, Inc. Seattle, WA venezia@zgi.com From owner-ageing@net.bio.net Sat Apr 01 23:00:00 1995 Path: biosci!agate!dog.ee.lbl.gov!news.cs.utah.edu!news.cc.utah.edu!corona!patrick From: Patrick O'Neil Newsgroups: bionet.molbio.ageing Subject: Re: Must an AGING PROCESS be universal? Date: Sun, 2 Apr 1995 15:10:34 -0600 Organization: University Of Utah Computer Center Lines: 52 Message-ID: References: <3lgf2r$dui@mserv1.dl.ac.uk> NNTP-Posting-Host: corona.med.utah.edu Mime-Version: 1.0 Content-Type: TEXT/PLAIN; charset=US-ASCII In-Reply-To: On Sun, 2 Apr 1995, Andrew K. Groves wrote: > In article , Patrick > O'Neil wrote: > > > The DNA and proteins that first made me no longer exist, as they were > > the precise strands of DNA and extant proteins within the zygote that led > > to me. Those original cells and their contents have long ceased to exist > > .... > > We are dealing with a problem of definition here. Dr. Bogler and myself > are using a set of precise definitions (which I will outline below) that > ...divide and rapidly fill up the area on the dish. At this point, they > will > stop dividing. They are said to be QUIESCENT. If you dissociate the cells > on the dish, and replate them at a lower density, the cells will start > dividing again... You can repeat this process between four and six > times (by > which time each of your founder cells will have divided probably between > 20 and 30 times). At this point, the cells once more stop dividing, and > become noticeably flattened. They cannot now be induced to divide any > more. They are said now to be SENESCENT. Senescent cells do not die... I apologize for picking at details, particularly amongst a group that basically knows what it is talking about (vs those in sci.cryonics and related). Even a senescent cell cannot continue indefinitely since stochastic processes, as well as environmental effectors work to cleave, dimerize, hydrolyze, radicalize, etc, etc, DNA, proteins, and lipids and that the cellular house-keeping genes and proteins are not 100% perfect in detection nor repair/maintenance. Thus, even a senescent cell is going to die no matter how well it is treated - BUT it is not, certainly, as subject to irreparable damage and alterations as is any actively replicating cell and is not subject to all the same problems. In the best of circumstances, a senescent cell may last a long time but it is definitely a finite period. The only way around this is, paradoxically, to divide, at least periodically, which brings the dangers inherent in THIS activity (base misincorporation, template slippage, insertions). Granted, this should all more likely be directed at another group - that might envision human immortality rather than a more realistic life extension or improvement in the quality of normal human lifespan, but it is these type of nitnoid details that I approach this area from; and from these little details, I try to pick out areas that might be exploitable or of interest (balancing just the right amount of replication with stasis - how and at what level would normal degradative processes be most optimally balanced though never defeated. From this, you could either obtain the most life-extension for the buck, as it were, or the best quality gains). If it seems that I am clouding the issue this is not my intent. Patrick From owner-ageing@net.bio.net Sat Apr 01 23:00:00 1995 Path: biosci!TENET.EDU!dashley From: dashley@TENET.EDU (Don Ashley) Newsgroups: bionet.molbio.ageing Subject: Quiescent/Senescent/Stochastic/Immortality Date: 2 Apr 1995 16:46:34 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 64 Sender: daemon@net.bio.net Distribution: world Message-ID: References: NNTP-Posting-Host: net.bio.net O'Neill enlightens the public about terms related to generic ambitions to arrest the aging process and extend lifespans an extra 100 years. The public must be informed of the concepts and terminology in order to promote govt'l funding and private investments for research. On Sun, 2 Apr 1995, Patrick O'Neil wrote: > > > On Sun, 2 Apr 1995, Andrew K. Groves wrote: > > In article , Patrick > > O'Neil wrote: > > > > > The DNA and proteins that first made me no longer exist, as they were > > > the precise strands of DNA and extant proteins within the zygote that led > > > to me. Those original cells and their contents have long ceased to exist > > > .... > > > > We are dealing with a problem of definition here. Dr. Bogler and myself > > are using a set of precise definitions (which I will outline below) that > > > ...divide and rapidly fill up the area on the dish. At this point, they > > will > > stop dividing. They are said to be QUIESCENT. If you dissociate the cells > > on the dish, and replate them at a lower density, the cells will start > > dividing again... You can repeat this process between four and six > > times (by > > which time each of your founder cells will have divided probably between > > 20 and 30 times). At this point, the cells once more stop dividing, and > > become noticeably flattened. They cannot now be induced to divide any > > more. They are said now to be SENESCENT. Senescent cells do not die... > > I apologize for picking at details, particularly amongst a group that > basically knows what it is talking about (vs those in sci.cryonics and > related). Even a senescent cell cannot continue indefinitely since > stochastic processes, as well as environmental effectors work to cleave, > dimerize, hydrolyze, radicalize, etc, etc, DNA, proteins, and lipids and > that the cellular house-keeping genes and proteins are not 100% perfect > in detection nor repair/maintenance. Thus, even a senescent cell is > going to die no matter how well it is treated - BUT it is not, certainly, > as subject to irreparable damage and alterations as is any actively > replicating cell and is not subject to all the same problems. In the > best of circumstances, a senescent cell may last a long time but it is > definitely a finite period. The only way around this is, paradoxically, > to divide, at least periodically, which brings the dangers inherent in > THIS activity (base misincorporation, template slippage, insertions). > Granted, this should all more likely be directed at another group - that > might envision human immortality rather than a more realistic life > extension or improvement in the quality of normal human lifespan, but it > is these type of nitnoid details that I approach this area from; and from > these little details, I try to pick out areas that might be exploitable > or of interest (balancing just the right amount of replication with > stasis - how and at what level would normal degradative processes be most > optimally balanced though never defeated. From this, you could either > obtain the most life-extension for the buck, as it were, or the best > quality gains). If it seems that I am clouding the issue this is not my > intent. > > Patrick > > From owner-ageing@net.bio.net Sat Apr 01 23:00:00 1995 Path: biosci!TENET.EDU!dashley From: dashley@TENET.EDU (Don Ashley) Newsgroups: bionet.molbio.ageing Subject: Senescence/Immortality Distinction Date: 2 Apr 1995 16:37:19 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 54 Sender: daemon@net.bio.net Distribution: world Message-ID: References: NNTP-Posting-Host: net.bio.net A clear differentiation follows from Groves: (comments welcome) On 2 Apr 1995, Andrew K. Groves wrote: > In article <-EwfvAeABh107h@chambers.ak.planet.co.nz>, > steve@chambers.ak.planet.co.nz (Steve Chambers) wrote: > > > > There's a tendency for those of us who've spent most of our studies > > in cellular and molecular biology to think that the term senescence > > (and by implication aging) only applies to cells. It doesn't - and > > for most of the community the terms apply principally to whole > > organisms. > > I agree. But the reason why much work has been done on cells is that they > represent a relatively simple way of examining the control of cell > division. > > > > The processes that dictate the "lifespan" of a cell or clone are but > > a small subset of those that should be examined when studying aging. > > > > Genetic control is plainly a major factor in cellular senescence but > > cellular senescence probably doesn't "explain why people die." There's > > a hackneyed quote in gerontology: "Nobody dies of old skin." > > > > You have to ask yourself a question: If current definitions of aging > > (including one that relies upon cellular senescence) don't "explain why > > people die" then how useful are they? > > I would suggest that one reason why we don't understand why people die is > that we don't understand the mechanisms of even simple systems such as > fibroblast senescence. You can define a phenomenon, but that is worlds > away from suggesting that you understand it. > > Another reason why simple culture models of cell growth are so popular is > that whilst "Nobody dies of old skin", a lot of people die of cancer, and > studies on cell division, senescence, transformation and death are a way > of getting at the molecular mechanisms of such processes. > > I'm not suggesting for a moment that other ways of thinking about ageing > are invalid. Quite the opposite. But part of the problem with the > discussion over the past few days is that people from different > backgrounds have been arguing about the meaning of concepts such as > immortality and senescence. Explaining one's own perspective may go some > way to clarifying the discussion. > > -- > Andy Groves > Division of Biology, 216-76 > California Institute of Technology > > From owner-ageing@net.bio.net Sat Apr 01 23:00:00 1995 Path: biosci!bloom-beacon.mit.edu!spool.mu.edu!uwm.edu!psuvax1!news.pop.psu.edu!hudson.lm.com!netline-fddi.jpl.nasa.gov!nntp-server.caltech.edu!NewsWatcher!user From: grovesa@starbase1.caltech.edu (Andrew K. Groves) Newsgroups: bionet.molbio.ageing Subject: Re: Must an AGING PROCESS be universal? Date: Sun, 02 Apr 1995 15:33:06 -0800 Organization: California Institute of Technology Lines: 29 Message-ID: References: <3lgf2r$dui@mserv1.dl.ac.uk> NNTP-Posting-Host: mac171.bio.caltech.edu In article , Patrick O'Neil wrote: > > I apologize for picking at details, particularly amongst a group that > basically knows what it is talking about (vs those in sci.cryonics and > related). ....... If it seems that I am clouding the issue this is not my > intent. > > Patrick Don't apologise! I certainly didn't intend to chastise you. My intention was to clarify what I saw as a confusion of terminology. That doesn't imply that anyone is right or wrong - I was just trying to explain what I understood by certain terms so that we weren't arguing about apples and oranges. In this instance, I was using a biological definition of immortality with regard to the capacity for cell division, and you were using the term in the more general (i.e. non-specialist) sense of "something that lives forever". That doesn't mean my definition is in some way 'better' than yours. They're just different. Cheers, Andy -- Andy Groves Division of Biology, 216-76 California Institute of Technology From owner-ageing@net.bio.net Sat Apr 01 23:00:00 1995 Path: biosci!bloom-beacon.mit.edu!spool.mu.edu!uwm.edu!fnnews.fnal.gov!nntp-server.caltech.edu!mac172.bio.caltech.edu!user From: grovesa@starbase1.caltech.edu (Andrew K. Groves) Newsgroups: bionet.molbio.ageing Subject: Re: Must an AGING PROCESS be universal? Date: 2 Apr 1995 22:02:03 GMT Organization: California Institute of Technology Lines: 39 Distribution: bionet Message-ID: References: <3ljpem$ldr@mserv1.dl.ac.uk> <3lmk3b$o03@news.halcyon.com> NNTP-Posting-Host: mac172.bio.caltech.edu In article <3lmk3b$o03@news.halcyon.com>, venezia@zgi.com (Domenick Venezia) wrote: > Andrew K. Groves (grovesa@starbase1.caltech.edu) wrote: > > Is senescence not a probabilistic process with a presumably gaussian > distribution? Don't we lose individual stem cells one at a time? The > stem cells left in a 120 year old are simply those few on the extreme > right of the distribution. Couldn't this be the reason our skins get > thinner, and our digestion gets poorer as we age? The number of stem > cells regenerating these tissues is less, and the tissue regeneration is no > longer as robust? So I think the Hayflick limit is active in human stem > cells, and isn't that the whole implicit assumption of the > telomere/telomerase work? That shortened telomeres lead to senescence > of stem cells and that the result of that senescence is the Hayflick > limit? If you have data that suggests that human stem cells in vivo are > in fact immortal I'd like to have a look at it, because it would completely > change the way myself and many others think about aging. > If you observe cell sensescence in culture, it certainly is not a probabilistic process - virtually all cells in a culture will drop out of the cell cycle within a few divisions of each other. The Hayflick limit has not been measured (to my knowledge) in human stem cells, partly because a) they are extremely difficult to identify and b) they are extremely difficult to propagate in culture in the way that Hayflick and others did for fibroblasts. I would say that the fact that 120 year olds have an intact gut at all would suggest that their crypt stem cells are working just fine - the human gut sheds an enormous number of cells every day (I think it's been estimated as 10 to the power of 11), and so any impairment of stem cell function would certainly compromise the integrity of this tissue very quickly indeed. -- Andy Groves Division of Biology, 216-76 California Institute of Technology From owner-ageing@net.bio.net Sat Apr 01 23:00:00 1995 Path: biosci!bloom-beacon.mit.edu!spool.mu.edu!howland.reston.ans.net!news.cac.psu.edu!news.pop.psu.edu!hudson.lm.com!netline-fddi.jpl.nasa.gov!nntp-server.caltech.edu!mac172.bio.caltech.edu!user From: grovesa@starbase1.caltech.edu (Andrew K. Groves) Newsgroups: bionet.molbio.ageing Subject: Re: Cellular senescence- is it aging? was Defining... Date: 2 Apr 1995 22:14:56 GMT Organization: California Institute of Technology Lines: 47 Message-ID: References: <-EwfvAeABh107h@chambers.ak.planet.co.nz> NNTP-Posting-Host: mac172.bio.caltech.edu In article <-EwfvAeABh107h@chambers.ak.planet.co.nz>, steve@chambers.ak.planet.co.nz (Steve Chambers) wrote: > There's a tendency for those of us who've spent most of our studies > in cellular and molecular biology to think that the term senescence > (and by implication aging) only applies to cells. It doesn't - and > for most of the community the terms apply principally to whole > organisms. I agree. But the reason why much work has been done on cells is that they represent a relatively simple way of examining the control of cell division. > The processes that dictate the "lifespan" of a cell or clone are but > a small subset of those that should be examined when studying aging. > > Genetic control is plainly a major factor in cellular senescence but > cellular senescence probably doesn't "explain why people die." There's > a hackneyed quote in gerontology: "Nobody dies of old skin." > > You have to ask yourself a question: If current definitions of aging > (including one that relies upon cellular senescence) don't "explain why > people die" then how useful are they? I would suggest that one reason why we don't understand why people die is that we don't understand the mechanisms of even simple systems such as fibroblast senescence. You can define a phenomenon, but that is worlds away from suggesting that you understand it. Another reason why simple culture models of cell growth are so popular is that whilst "Nobody dies of old skin", a lot of people die of cancer, and studies on cell division, senescence, transformation and death are a way of getting at the molecular mechanisms of such processes. I'm not suggesting for a moment that other ways of thinking about ageing are invalid. Quite the opposite. But part of the problem with the discussion over the past few days is that people from different backgrounds have been arguing about the meaning of concepts such as immortality and senescence. Explaining one's own perspective may go some way to clarifying the discussion. -- Andy Groves Division of Biology, 216-76 California Institute of Technology From owner-ageing@net.bio.net Sun Apr 02 23:00:00 1995 Newsgroups: bionet.molbio.ageing From: John@longevb.demon.co.uk (John de Rivaz) Path: biosci!agate!spool.mu.edu!uwm.edu!cs.utexas.edu!swrinde!pipex!peernews.demon.co.uk!longevb.demon.co.uk!John Subject: Re: Must an AGING PROCESS be universal? was Defining... References: <3lgf2r$dui@mserv1.dl.ac.uk> Organization: Myorganisation Reply-To: John@longevb.demon.co.uk X-Newsreader: Newswin Alpha 0.7 Lines: 20 X-Posting-Host: longevb.demon.co.uk Date: Mon, 3 Apr 1995 06:43:59 +0000 Message-ID: <397138810wnr@longevb.demon.co.uk> Sender: usenet@demon.co.uk In article: <3lgf2r$dui@mserv1.dl.ac.uk> writes: > There are plants (ferns and trees) that live for thousands of years. In > such plants, however, each dividing cell has a life which is probably ^^^^^^^^ > much shorter, similar to the situation in the bacterial colony. > Has anyone any hard facts on this? It looks as though this is an important point. -- Sincerely, **************************************** * Publisher of Longevity Report * John de Rivaz * Fractal Report * * details on request * **************************************** **** What is the point of life if it ends in death? **** From owner-ageing@net.bio.net Sun Apr 02 23:00:00 1995 Path: biosci!agate!howland.reston.ans.net!pipex!uknet!daresbury!not-for-mail From: Newsgroups: bionet.molbio.ageing Subject: Re: Must an AGING PROCESS be universal? Date: 3 Apr 1995 10:03:44 +0100 Lines: 90 Sender: lpddist@mserv1.dl.ac.uk Distribution: bionet Message-ID: <3lodlg$5hp@mserv1.dl.ac.uk> Original-To: AGEING@dl.AC.UK The next question is how old do individual cells really get. I would like to ask for sound proof, derived from individually tagged cells, showing their age. Andy thinks that the stem cells in the intestine live as long as the individual human being. If this is true the maximum age of an individual cell is at least 120 years. Can anyone add to this list, but please only when also quoting the paper in which it has been published. For me the list has not yet started, as I would like to know whether the intestine stem cells live that long for a fact. > > We are dealing with a problem of definition here. [We] are using a set of precise definitions (which I will outline below) that are used by biologists working on the problems of cell division. > > If you take a population of embryonic rat fibroblasts .. and grow them in a culture dish, you will notice that the cells > divide and rapidly fill up the area on the dish. At this point, they will > stop dividing. They are said to be QUIESCENT. If you dissociate the cells > on the dish, and replate them at a lower density, the cells will start > dividing again. You can repeat this process between four and six times (by > which time each of your founder cells will have divided probably between > 20 and 30 times). At this point, the cells once more stop dividing, and > become noticeably flattened. They cannot now be induced to divide any > more. They are said now to be SENESCENT. Senescent cells do not die - they > just sit there and carry on metabolising but cannot divide any further. We > would interpret this phenomenon by saying that the cells we isolated from > the rat embryos have a finite limit to the number of divisions they can > undergo. This will tend to be roughly the same number in every experiment > you perform. > > It is possible to carry out manipulations whilst these cells are still > dividing that will override their limit to cell division. This can be done > by, for example, introducing certain oncogenes such as v-myc, or the SV40 > large T antigen. The cells will now continue to divide in culture > indefinitely and will not respect their normal limited number of > divisions. We call these cells IMMORTAL, in that they can be propagated > indefinitely in culture, and the oncogenes that cause these effects > IMMORTALISING ONCOGENES. Note that this is a narrow but precise definition > of the word immortal used by biologists. > > My point here is that biologists tend to define immortal cells NOT as > cells that 'live forever', but as {cells} that have no intrinsic limit to > the number of divisions they can undergo. This is in stark contrast to > most normal cells, which appear to have a pre-programmed number of cell > divisions. Stem cells do not appear have a limit to the number of > divisions they can undergo. > As to this last paragraph, Andy, do you really mean cells or cell lines. See the word cells that I placed between marks. Best regards, Wouter van Doorn ATO-DLO, Wageningen, Holland > Return-path: > Received: from AGRO02 by ATO.AGRO.NL (PMDF V4.3-7 #7552) > id <01HOV9EMO7740013G2@ATO.AGRO.NL>; Sun, 2 Apr 1995 15:20:08 GMT > Received: from mserv1.dl.ac.uk by AGRO.NL (PMDF V4.2-12 #4885) > id <01HOV9E4W94G000NCQ@AGRO.NL>; Sun, 2 Apr 1995 15:19:44 MET > Received: by mserv1.dl.ac.uk id NAA22053 > (8.6.10/5.3[ref postmaster@dl.ac.uk] for dl.ac.uk from server-daemon@dl.ac.uk) > ; Sun, 2 Apr 1995 13:22:10 +0100 > Received: by mserv1.dl.ac.uk id JAA12470 > (8.6.10/5.3[ref postmaster@dl.ac.uk] for dl.ac.uk from server-daemon@dl.ac.uk) > ; Sun, 2 Apr 1995 09:13:09 +0100 > Received: by mserv1.dl.ac.uk id JAA12433 > (8.6.10/5.3[ref postmaster@dl.ac.uk] for dl.ac.uk from news@dl.ac.uk); Sun, > 2 Apr 1995 09:11:31 +0100 > Resent-date: Sun, 02 Apr 1995 13:22:10 +0000 (UT) > Date: Sun, 02 Apr 1995 00:06:30 -0800 > Resent-from: server-daemon@dl.ac.uk > From: grovesa@starbase1.caltech.edu (Andrew K. Groves) > Subject: Re: Must an AGING PROCESS be universal? > Sender: "bionet.molbio.ageing mail newsgroup" > To: "bionet.molbio.ageing mail newsgroup" > Reply-to: grovesa@starbase1.caltech.edu (Andrew K. Groves) > Resent-message-id: > Message-id: <9542132210.~INN-RLAa00165.bionet-news@dl.ac.uk> > X-Mailer: MXT V 12.16.1 > Content-transfer-encoding: 7BIT > Precedence: list > X-Article-Number: bionet.molbio.ageing Msg # 1355 > X-Listpath: bionet-news > Comments: List problems/queries to > Comments: To mail both the group and netnews send to (ageing@dl.ac.uk) > From owner-ageing@net.bio.net Sun Apr 02 23:00:00 1995 Path: biosci!bcm!cs.utexas.edu!howland.reston.ans.net!news.moneng.mei.com!uwm.edu!fnnews.fnal.gov!nntp-server.caltech.edu!mac172.bio.caltech.edu!user From: grovesa@starbase1.caltech.edu (Andrew K. Groves) Newsgroups: bionet.molbio.ageing Subject: Re: Must an AGING PROCESS be universal? Date: 3 Apr 1995 22:09:51 GMT Organization: California Institute of Technology Lines: 47 Distribution: bionet Message-ID: References: <3lodlg$5hp@mserv1.dl.ac.uk> NNTP-Posting-Host: mac172.bio.caltech.edu In article <3lodlg$5hp@mserv1.dl.ac.uk>, wrote: > The next question is how old do individual cells really get. I wouldlike > to ask for sound proof, derived from individually tagged cells, showing > their age. Andy thinks that the stem cells in the intestine live as long > as the individual human being. If this is true the maximum age of an > individual cell is at least 120 years. Can anyone add to this list, but > please only when also quoting the paper in which it has been > published. For me the list has not yet started, as I would like to know > whether the intestine stem cells live that long for a fact. > I think there is a misunderstanding here, although I'm not sure. A gut stem cell (to use the above example) divides, giving rise to two daughter cells - one of which is another stem cell, the other will go on and give rise to differentiated cells in the gut wall. So an 'individual' cell doesn't live for 120 years, although the propagation of the stem cell population does indeed occur, presumably as long as the gut remains intact. I don't see how you could do the tagging experiment you propose, not least because gut stem cells have never been unequivocally identified - their existence is inferred from the kinetics of gut wall shedding and renewal. As far as normal cells (as opposed to cell lines) being propagated beyond their normal limit, there is a fair amount of data that this can be achieved in culture. For example, glial progenitor cells (O-2A cells) can be grown in culture, but they normally tend to differentiate and stop dividing after a period of (about ) 10 divisions. If, on the other hand you grow similar primary cultures of these cells in a combination of platelet-derived growth factor and fibroblast growth factor, they can be propagated for months. If you withdraw these factors, the cells tend to differentiate immediately, suggesting that the effect of these two factors is reversible. It has been possible to expand such glial precursors, and to transplant them into animals, where they appear to differentiate normally without giving tumours. But this is more Oliver Bogler's speciality than mine, so I'll leave it to him to elaborate further if he sees fit. Regards, Andy Groves -- Andy Groves Division of Biology, 216-76 California Institute of Technology From owner-ageing@net.bio.net Sun Apr 02 23:00:00 1995 Newsgroups: bionet.molbio.ageing Path: biosci!bcm!cs.utexas.edu!swrinde!howland.reston.ans.net!ix.netcom.com!netcom.com!luly From: luly@netcom.com (Robert Luly) Subject: Homocysteine/Macular degen? Message-ID: Organization: NETCOM On-line Communication Services (408 261-4700 guest) X-Newsreader: TIN [version 1.2 PL1] Date: Mon, 3 Apr 1995 17:04:49 GMT Lines: 10 Sender: luly@netcom5.netcom.com Homocysteine is a "vascular toxin". Homocysteine levels elevate in most individuals as they grow older. Macular degeneration has a vascular componet. 1. Circumstantial evidence exists that suggests there could be a connection between Homocysteine and macular degeneration. 2. Has there been any published or unpublished research regarding this subject? -- luly@netcom.com From owner-ageing@net.bio.net Sun Apr 02 23:00:00 1995 Newsgroups: bionet.molbio.ageing Path: biosci!agate!howland.reston.ans.net!pipex!oleane!jussieu.fr!univ-lyon1.fr!swidir.switch.ch!scsing.switch.ch!rzusuntk.unizh.ch!NewsWatcher!user From: maga@vetbio.unizh.ch (Giovanni Maga) Subject: Re: Cellular senescence- is it aging? was Defining... Message-ID: Followup-To: bionet.molbio.ageing Sender: newsadm@rzu-news.unizh.ch (CNEWS ADMINISTRATION) Organization: University of Zurich Irchel- Biochemistry References: <-EwfvAeABh107h@chambers.ak.planet.co.nz> Date: Mon, 3 Apr 1995 17:48:37 GMT Lines: 18 In article <-EwfvAeABh107h@chambers.ak.planet.co.nz>, steve@chambers.ak.planet.co.nz (Steve Chambers) wrote: (omissis) > > You have to ask yourself a question: If current definitions of aging > (including one that relies upon cellular senescence) don't "explain why > people die" then how useful are they? > > Steve > But you can think that people die for a series of damages which can be related at last to cell death. Massive cell death will compromise the function of essential organs leading to organism's death. I think that we must still go on studying cell death but (as you pointed out) with an eye at the context in which these cells are located in living organisms. maga@vetbio.unizh.ch From owner-ageing@net.bio.net Mon Apr 03 23:00:00 1995 Path: biosci!daresbury!not-for-mail From: Newsgroups: bionet.molbio.ageing Subject: Re: Must an AGING PROCESS be universal? Date: 4 Apr 1995 04:30:52 +0100 Lines: 17 Sender: lpddist@mserv1.dl.ac.uk Distribution: bionet Message-ID: <3lqehc$l3b@mserv1.dl.ac.uk> Original-To: ageing@dl.AC.UK Andy - part of my last message was not kept, for some reason. I began with a paragraph in which I said I appreciated your definitions, which were quoted below. I accept that biologists working on cell division call cell lines that do not stop replicating to be 'immortal'. I am also a biologist, and would rather define 'immortal' (if I would use the word at all) for an individual cell or an individual polycellular orga- nism. The word immortal, however, is not very exact as it is not easy to prove. Thank you for explaining the terminology of biologists working on cell lines. It clearly helps the discussion. Wouter van Doorn ATO-DLO, Wageningen, The Netherlands. From owner-ageing@net.bio.net Mon Apr 03 23:00:00 1995 Path: biosci!bcm!cs.utexas.edu!news.tamu.edu!news.utdallas.edu!news.starnet.net!wupost!waikato!auckland.ac.nz!kcbbs!planet!chambers!steve From: steve@chambers.ak.planet.co.nz (Steve Chambers) Newsgroups: bionet.molbio.ageing Subject: Re: Must an AGING PROCESS be universal? was Defining... Message-ID: Date: Tue, 4 Apr 95 13:57:33 +1200 Organization: PlaNet (Auckland New Zealand) Lines: 113 Earlier I wrote: > We may all rely on the same processes, but there's considerable > variability in how much and how well we use them. Your heart disease > through fat example illustrates this. The APOE (apolipoprotein E) gene > has several alleles but one (e4) is associated with early atherosclerosis > and another (e2) is associated with hyperlipidemia. Get two copies of > the e3 allele and you'll probably never suffer atherosclerosis no > matter how much fat you eat. Since I wrote this, I've discovered a paper in Nature Genetics that shows that the effects of these alleles are not at all what might have been predicted from earlier studies. It seems that having e2 gives you TWICE the chance of making it to 100. Wacky huh? Hold that fat. This doesn't change my comments on the role of non-universal intrinsic differences in the aging of individuals but it does illustrate how difficult it will be to isolate individual processes: Like atherosclerosis most processes will be seriously polygenic. Which brings me to comments by Chris Driver In drierac@deakin.edu.au (Chris Driver) writes: >In article <3ZGevA7CBh107h@chambers.ak.planet.co.nz> steve@chambers.ak.planet.co.nz (Steve Chambers) writes: >>That doesn't necessarily follow, especially if there were enough of 'em >>and they were all "common". To illustrate the point let's assume there >>are 100 aging processes (I believe there are more) and any human has a >>30% chance of each. Assuming random distribution the prob. of being subject >>to no process is 0.7^100 or one chance in around 30,000,000,000,000,000. >>It's not going to happen very often. >>The above dynamic may explain lifespan distribution, or it may not. By >>saying that an aging process NEED not be universal I certainly don't mean >>to imply that NO aging process is universal. >I am not convinced: it should be possible to select for absence of A, then B >then C and produce an animal which lives very much longer. 1) To select for the absence of A you first need to know what A is. 2) You then need to find some way of selecting for [not A]. That could be a difficult (and expensive task). As an exercise, think of an easy way to select for APOE allele e3 in the above example. 3) Once you get to M you may still find that you've failed to increase maximum lifespan (in much the same way that medicine has failed to increase it for humans). Funding by now would be a serious problem. 4) When you've finally selected for [not A-M] you'll almost certainly have removed alleles necessary for several of [not N thru Z ...] Possible? Maybe, but certainly not practical and: 5) If no process turns out to be universal (not a chance) and by some miracle you succeed in isolating an "immortal" mutant, what you've discovered will only be partly applicable to human beings. And remember, to even get to step (1) science will need to accept a a radical redefinition of what constitutes an aging process. >In fact if you select for longevity in Drosophila, you can easily >obtain a modest increase in lifespan and then you hit a wall. That's not surprising, and it fits well with a multiple process model, as does Carey et al's medfly study where death rates are dramatically _reduced_ at old age in large cohorts. >Perhaps you accept a modified version. There are a number of deteriorative >processes which effect everybody, although the relative rate of progression is >slower in some than others. For instance cardiovascular degeneration occurs in >all people, but in some it is so slow that they die of something else first. >This means that cardiovascular disease is one ageing process. Cardiovascular disease is too broad an example. It's no doubt contributed to by several processes - some of which will be universal. Its biggest contributor, the formation of atheroma is different story, however. It's common but not universal in humans and it occurs in very few animal species - so its (hopefully few) component processes are plainly not universal. But I agree that variation in process rate will probably explain most of the heterogeneity we see in aging. And finally... There's been some discussion at crossed purposes since my initial post on defining aging processes. These comments describe my understanding of the terms I use - perhaps they should have been an addendum. Aging or ageing is that universal phenomenon that unless otherwise specified applies to whole organisms. Senescence - ditto, but it can also refer to clones or cell cultures. Cellular senescence for me is just that - cellular senescence. I know that the "cellular" is usually redundant between molecular biologists but I try never to drop it - or I'll lose sight of the "big picture". I never use the term immortal to refer to a cell because there's no such thing. I might call it immortalised, but that's descriptive of a change it's been through and quite a different matter. A cell line or clone can be immortal however. Downunder English is it's own entity variously influenced by English English and American English and scientific Downunder English is very much flavoured by the usage (or lack thereof) of local scientists. I can remember one of my lecturers, for example, not knowing what the term "Hayflick limit" meant. He'd just finished discussing doubling potential! Someone tell me if my use of these terms is inappropriate. Steve -- ________________________ (I_lurk,_therefore_I_am!_\ ,,, Steve Chambers (o o) steve@chambers.ak.planet.co.nz ----------------------oOO--(_)--OOo----------------------------- (c) Steve Chambers 1995. All rights reserved ---------------------------------------------------------------- From owner-ageing@net.bio.net Mon Apr 03 23:00:00 1995 Path: biosci!galaxy.ucr.edu!ihnp4.ucsd.edu!network.ucsd.edu!licr-user003.ucsd.edu!user From: obogler@ucsd.edu (Oliver Bogler) Newsgroups: bionet.molbio.ageing Subject: Re: Must an AGING PROCESS be universal? Date: Mon, 03 Apr 1995 13:15:28 -0700 Organization: Ludwig Institute Lines: 36 Distribution: bionet Message-ID: References: <3ljpem$ldr@mserv1.dl.ac.uk> <3lmk3b$o03@news.halcyon.com> NNTP-Posting-Host: licr-user003.ucsd.edu In article <3lmk3b$o03@news.halcyon.com>, venezia@zgi.com (Domenick Venezia) wrote: > Is senescence not a probabilistic process with a presumably gaussian > distribution? Don't we lose individual stem cells one at a time? The > stem cells left in a 120 year old are simply those few on the extreme > right of the distribution. Couldn't this be the reason our skins get > thinner, and our digestion gets poorer as we age? The number of stem > cells regenerating these tissues is less, and the tissue regeneration is no > longer as robust? So I think the Hayflick limit is active in human stem > cells, and isn't that the whole implicit assumption of the > telomere/telomerase work? That shortened telomeres lead to senescence > of stem cells and that the result of that senescence is the Hayflick > limit? If you have data that suggests that human stem cells in vivo are > in fact immortal I'd like to have a look at it, because it would completely > change the way myself and many others think about aging. Cellular senescence does not appear to be probalistic in the sense that a cell has a given probability of senescing per division. In fact whole populations of cells senesce near-simultaneously in some model systems (eg. rodent embryo fibroblasts) which has led to the suggestion that a cellular clock regulates the onset of senescence. This is the main line of work that supports the view that cellular senescence, and so possibly organismal ageing, is an active process rather than the random accumulation of damage. The telomere hypothesis is one possible mechanism by which the postulated cellular clock could operate. At the moment the data are only correlative: telomere length/telomerase activity and expecte cellular lifespan correlate. But I need hardly say that that is not proof of causation. As to data that says that human stem cells *in vivo* are immortal - a bit hard to come by? Once we know what the basis of the Hayflick limit is, we could more easily go look. Oliver From owner-ageing@net.bio.net Mon Apr 03 23:00:00 1995 Path: biosci!ESSEX.HSC.COLORADO.EDU!kruged From: kruged@ESSEX.HSC.COLORADO.EDU (Edward Krug) Newsgroups: bionet.molbio.ageing Subject: Re: Must an AGING PROCESS be universal? Date: 4 Apr 1995 00:30:09 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 27 Sender: daemon@net.bio.net Distribution: world Message-ID: References: <954403451.~INN-VKBa00165.bionet-news@dl.ac.uk> NNTP-Posting-Host: net.bio.net Much has been made of the Hayflick limit for fibroblasts in cell culture. For my own purposes human fibroblasts beyond 35 doublings in cell culture are unusable, and I have seen cells grow "old" many times. Although this senescence is ascribed as an intrinsic aspect of these cells, I can't help but wonder if growing a single cell type in a monolayer in media which dosen't present diurnal and shorter variations in temperature, nutrients, hormones, immune cell survelence, trophic factors (both circulating and directly delivered), all these and probably a few more might actually obscure the true potential of these cells. We don't know all the factors which lead to the differentiation of pleupotent stem cells into fibroblasts, some of which apparently need be delivered by cell-to-cell contact. The cells which display a Hayflick limit may in fact be cells which need their enviromental clues for maintenance, and in culture they are just coasting, slowly coming to a stop. I work on getting parasitic protozoa which infect humans cells to grow in cell culture. It is painfully obvious that the conditions we can generate in culture don't match those in vivo. I am making this posting to argue that the Hayflick limit may be an artifact of incomplete knowledge of cell vitality requirements. Then again, the decline in the supply of those requirements in the whole animal may be a part of the "ageing process". Edward C. Krug e-mail =kruged@essex.hsc.colorado.edu Univ. of Colorado Med. School From owner-ageing@net.bio.net Mon Apr 03 23:00:00 1995 Path: biosci!agate!howland.reston.ans.net!news.moneng.mei.com!news.ecn.bgu.edu!psuvax1!news.cc.swarthmore.edu!netnews.upenn.edu!Lehigh.EDU!Lehigh.EDU!not-for-mail From: x011@Lehigh.EDU Newsgroups: bionet.molbio.ageing Subject: inderal? Date: 4 Apr 1995 08:36:24 -0400 Lines: 2 Message-ID: <3lreg8$3q18@ns1.CC.Lehigh.EDU> NNTP-Posting-Host: ns1.cc.lehigh.edu My wife has been taking inderal for at least 10 years. It looks like she has not aged a day. Is there any connection? Ron Blue From owner-ageing@net.bio.net Mon Apr 03 23:00:00 1995 Path: biosci!galaxy.ucr.edu!ihnp4.ucsd.edu!network.ucsd.edu!licr-user003.ucsd.edu!user From: obogler@ucsd.edu (Oliver Bogler) Newsgroups: bionet.molbio.ageing Subject: Re: Must an AGING PROCESS be universal? Date: Tue, 04 Apr 1995 10:58:40 -0700 Organization: Ludwig Institute Lines: 31 Distribution: bionet Message-ID: References: <3lodlg$5hp@mserv1.dl.ac.uk> NNTP-Posting-Host: licr-user003.ucsd.edu In article <3lodlg$5hp@mserv1.dl.ac.uk>, wrote: > The next question is how old do individual cells really get. I would like > to ask for sound proof, derived from individually tagged cells, showing > their age. Andy thinks that the stem cells in the intestine live as long > as the individual human being. If this is true the maximum age of an > individual cell is at least 120 years. Can anyone add to this list, but > please only when also quoting the paper in which it has been > published. For me the list has not yet started, as I would like to know > whether the intestine stem cells live that long for a fact. This experiment is undoable, or needs redefining. The only part of a cell that is truly immortal is the DNA sequence - you could tag the DNA of a stem cell at birth and see if the tag is still there at age 120. If it is, it will be in a cell derived from the tagged cell - and you will be able to conclude that the lineage is continuous and so that the first cell was immortal (The rest of the cell (the proteins, the membranes etc. etc.) is long turned over. Of course the atoms in the DNA as well - just the sequence will be the same.) But to me that is no different from saying that the stem cell that divides at age 120 is immortal because by definition it is derived from a cell that was onboard at birth. You only get cells from other cells - they are not ever made de novo. So the experiment would be to see whether there are any dividing stem cells at age 120 - and that is all. Its immortality, by the way, does not mean that it will not produce daughters that are mortal. Oh by the way - could we all post to the group, please - it is a bit like listening to one side of a phone conversation right now. Oliver From owner-ageing@net.bio.net Tue Apr 04 23:00:00 1995 Path: biosci!bcm!cs.utexas.edu!howland.reston.ans.net!vixen.cso.uiuc.edu!uwm.edu!fnnews.fnal.gov!nntp-server.caltech.edu!mac172.bio.caltech.edu!user From: grovesa@starbase1.caltech.edu (Andrew K. Groves) Newsgroups: bionet.molbio.ageing Subject: Re: Must an AGING PROCESS be universal? Date: 5 Apr 1995 03:27:24 GMT Organization: California Institute of Technology Lines: 32 Distribution: bionet Message-ID: References: <3lqehc$l3b@mserv1.dl.ac.uk> NNTP-Posting-Host: mac172.bio.caltech.edu In article <3lqehc$l3b@mserv1.dl.ac.uk>, wrote: > Andy - part of my last message was not kept, for some reason. I began >with > a paragraph in which I said I appreciated your definitions, which > were quoted below. I accept that biologists working on cell division > call cell lines that do not stop replicating to be 'immortal'. I am > also a biologist, and would rather define 'immortal' (if I would use the > word at all) for an individual cell or an individual polycellular orga- > nism. The word immortal, however, is not very exact as it is not easy to > prove. > > Thank you for explaining the terminology of biologists working on cell > lines. It clearly helps the discussion. > Sorry about the confusion with the last message! I think your last point is well taken with respect to dealing with stem cells in vivo. As Potten and Loeffler pointed out in an excellent review on stem cells a few years back, there are great difficulties in trying to interact experimentally with stem cells, as you may change their behaviour in the process. They referred to this as Heisenberg's Uncertainty Priciple operating in a biological context, which I think is a very interesting idea! Best wishes, Andy -- Andy Groves Division of Biology, 216-76 California Institute of Technology From owner-ageing@net.bio.net Tue Apr 04 23:00:00 1995 Newsgroups: bionet.molbio.ageing Subject: Re: Must an AGING PROCESS From: david.lloyd-jones@canrem.com (David Lloyd-Jones) Path: biosci!bcm!cs.utexas.edu!howland.reston.ans.net!torn!news.uunet.ca!uunet.ca!portnoy!canrem.com!david.lloyd-jones Distribution: world Message-ID: <60.762.4045.0N1D9C9C@canrem.com> References: <397138810wnr@longevb.demon.co.uk> Date: Tue, 4 Apr 95 21:13:00 -0500 Organization: CRS Online (Toronto, Ontario) Lines: 30 John@longevb.demon.co.uk asks: JD+In article: <3lgf2r$dui@mserv1.dl.ac.uk> +writes: +> There are plants (ferns and trees) that live for thousands of years. In +> such plants, however, each dividing cell has a life which is probably + ^^^^^^^^ +> much shorter, similar to the situation in the bacterial colony. +> JD+Has anyone any hard facts on this? It looks as though this is an important +point. John, Van Doorn has just presented the hard fact, elegantly and succinctly stated. I think it's a testimony to the Net's degradation that you don't recognise one when you see it. His use of the word "probably", which you underline as though it were something odd, simply adds to the accuracy of the whole statement. -dlj. david.lloyd-jones@canrem.com * 1st 1.11 #3818 * "640k should be enough for anybody" - Bill Gates, 1981. From owner-ageing@net.bio.net Thu Apr 06 23:00:00 1995 Path: biosci!bcm!cs.utexas.edu!howland.reston.ans.net!news.cac.psu.edu!news.pop.psu.edu!hudson.lm.com!newsfeed.pitt.edu!uunet!munnari.oz.au!newsroom.utas.edu.au!mg1_98.plant.utas.edu.au!user From: sj_skabo@postoffice.utas.edu.au (Stuart Skabo) Newsgroups: bionet.molbio.ageing Subject: Info: Oxidative Damage and Aging Followup-To: bionet.molbio.ageing Date: 7 Apr 1995 04:27:19 GMT Organization: Mol Biol Unit, Uni of Tasmania Lines: 15 Distribution: world Message-ID: NNTP-Posting-Host: mg1_98.plant.utas.edu.au Hoi All, I am an honours student at the university of Tasmania, Australia and i am doing an essay, "Can degenerative diseases and aging be attributed to damage by reactive oxygen molecules?". I am after references, other information sources and associated comment on this topic and am willing to post the results of this request and all the material i gathered on my own to the group or communicate with interested parties. I would be greatly appreciative of any help i receive, and can be contacted at the address below. Thank you for your time, Stuart Email: sj_skabo@postoffice.utas.edu.au From owner-ageing@net.bio.net Thu Apr 06 23:00:00 1995 Path: biosci!SINGER.ASRI.EDU!MANEV From: MANEV@SINGER.ASRI.EDU ("Hari Manev, M.D.") Newsgroups: bionet.molbio.ageing Subject: CALL FOR ABSTRACTS/POSTERS: OXIDATIVE STRESS, APOPTOSIS & BRAIN DAMAGE Date: 7 Apr 1995 14:17:48 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 4 Sender: daemon@net.bio.net Distribution: world Message-ID: <01HP2AKLZOR6003ST9@SINGER.ASRI.EDU> NNTP-Posting-Host: net.bio.net International Symposium on Oxidative Stress, Apoptosis and Brain Damage will be held in Pittsburgh, PA, USA, Sept 21-24, 1995. Twenty invited speakers! The deadline for abstracts is May 31. For the brochure and abstract forms fax: +412-359-4364 or e-mail: manev@singer.asri.edu From owner-ageing@net.bio.net Sat Apr 08 23:00:00 1995 Path: biosci!bloom-beacon.mit.edu!gatech!howland.reston.ans.net!agate!sunsite.doc.ic.ac.uk!doc.news.pipex.net!pipex!oleane!jussieu.fr!univ-lyon1.fr!swidir.switch.ch!scsing.switch.ch!news.belwue.de!fu-berlin.de!fub46.fddi1.fu-berlin.DE!not-for-mail From: Andreas Kage Newsgroups: bionet.molbio.ageing Subject: Quantification of morbidity in a population Date: Sun, 9 Apr 1995 19:23:44 +0000 Organization: Freie Universitaet Berlin Lines: 22 Message-ID: NNTP-Posting-Host: fub46.fddi1.fu-berlin.de (160.45.1.46) Mime-Version: 1.0 Content-Type: TEXT/PLAIN; charset=US-ASCII X-Access: 16 17 19 There are many reports that with ongoing age there is an increase of morbidity. If you want to define reference ranges for clinical decision support then you have to define a 'healthy' reference population. Two aspects of increase in morbidity can be discussed: (a) the number of persons in the population increase or (b) the quality of morbidity in a person increases. If you want to demonstrate that a clinical measure is related to morbidity than you need a quantification of the morbidity of an individuum. Has anybody an idea how to quantify morbidity ? Thanks for discussion Andreas Andreas Kage | UKRV-IKC Phone: +49 (0)30 3035 3405 | Spandauer Damm 130 E-Mail: akage@fub46.zedat.fu-berlin.de | 14050 Berlin From owner-ageing@net.bio.net Sat Apr 08 23:00:00 1995 Path: biosci!daresbury!not-for-mail From: Newsgroups: bionet.molbio.ageing Subject: Must an AGING PROCESS be universal? Date: 8 Apr 1995 14:36:26 +0100 Lines: 43 Sender: lpddist@mserv1.dl.ac.uk Distribution: bionet Message-ID: <3m63gq$482@mserv1.dl.ac.uk> Original-To: AGEING@dl.AC.UK In a discussion about the definition of immortality Oliver Bogler wrote: > > But to me that is no different from saying that the stem cell that divides > at age 120 is immortal because by definition it is derived from a cell > that was onboard at birth. You only get cells from other cells - they are > not ever made de novo. So the experiment would be to see whether there are > any dividing stem cells at age 120 - and that is all. > I have serious difficulty with this definition. We do not know how long an individual stem cell lives. The parent cell may divide and then fully differentiate, i.e. until death. The daughter cell does the same, etc. Each individual cell may live for a few days only. Yet you call the cell immortal. In this definition a cell is immortal when its descendants keep multiplying. As someone else has said, this would imply, logically, that the only immortal cell was the first one. Bacteria, which will go on multiplying when regularly placed on a new substrate, would in this line of thinking also be called immortal, although we know for a fact that each cell only lives for a day or two. Also human beings would then be immortal, since they have ever been multiplying (with some success). This shows that the definition defies common sense. I could agree with calling a cell culture immortal, but there is some hybris in the word. Isn't it a bit exaggerated? How could we prove it? Things that cannot be proven or disproven are outside the realm of science. The term, therefore, is unscientific. Best regards, Wouter van Doorn ATO-DLO, Wageningen, Holland ----- End forwarded message From owner-ageing@net.bio.net Sat Apr 08 23:00:00 1995 Path: biosci!news.cs.umb.edu!oitnews.harvard.edu!rutgers!uwm.edu!hookup!newshost.marcam.com!uunet!in1.uu.net!maple.enet.net!not-for-mail From: oceania@news.enet.net (Eric Klien) Newsgroups: bionet.molbio.ageing,sci.life-extension,sci.cryonics Subject: ANNOUNCE: World Health Net Moves! Date: 8 Apr 1995 17:02:42 -0700 Organization: Evergreen Communications Phoenix, AZ Lines: 11 Message-ID: <3m7872$li@pinyon.enet.net> NNTP-Posting-Host: pinyon.enet.net Xref: biosci bionet.molbio.ageing:1672 sci.life-extension:4628 sci.cryonics:1904 WEB SITE ANNOUNCMENT World Health Net has moved to its permanent location! This multimedia web site is home of the latest and most innovative research therapies. The American Academy of Anti-Aging Medicine, American Longevity Research Institute, High Technology Research Institute, Longevity Institute International, and the National Academy of Sports Medicine are on this site. (Life Resucitation Technologies, Inc. and Organ, Inc. have been moved due to a private offering in progress.) Many medical resources plus a medical mailing list are available on this site. Our address is http://world-health.net/ From owner-ageing@net.bio.net Sat Apr 08 23:00:00 1995 Path: biosci!agate!howland.reston.ans.net!vixen.cso.uiuc.edu!news.uoregon.edu!news.xmission.com!news.cc.utah.edu!corona!patrick From: Patrick O'Neil Newsgroups: bionet.molbio.ageing Subject: Telomeres Date: Sun, 9 Apr 1995 13:15:41 -0600 Organization: University Of Utah Computer Center Lines: 75 Message-ID: NNTP-Posting-Host: corona.med.utah.edu Mime-Version: 1.0 Content-Type: TEXT/PLAIN; charset=US-ASCII I am working on a research proposal for the study of telomere length regulation. Since telomerase activity is constant in germ cells, stem cells, and in a perhaps abnormal way in certain cancer cells, the question arises as to what prevents telomeres from extending indefinitely. Telomerase activity in the above mentioned cell types appears to be independent of cell cycle position, with telomerase activity throughout S and M phase. Therefore, cell cycle regulatory proteins do not appear to affect telomerase transcription levels...so how are telomeres maintained at a rather stable length? (All within a heterogenous but rather narrow range of several kb) My thoughts: 1) The level of telomerase transcription is under two layers of control: self regulated by feedback loop and developmentally regulated - for permanent silencing upon differentiation of a stem cell into a somatic tissue cell. If telomerase levels are low in general in, say, stem cells, then kinetically the enzyme may be constantly operating in a balance with cell division so that shortening due to division and normal degredation is balanced by extension. Thus telomerase is limiting. If this is the case, then the process is saturable so that if a lot of telomeric seed sequence is added to such a cell, then all telomeres should shorten and ultimately stabilize at a shorter length. 2) Telomere binding factors (proteins and ribonucleoproteins) act to regulate telomere length. I see that this could take place in two ways: Telomerase is a multisubunit enzyme. If any of its subunits are limiting, then the overall activity of the enzyme is limited by subunit levels as in 1 above. Alternatively, if such telomere binding species act to protect telomeres from degradation, and they are produced at a constant level so that an equilibrium is attained, then extension of telomere beyond a point at which there is enough binding factors to bind and protect the sequence would be automatically degraded back to protection levels. This would be a dynamic process in which telomerase constantly adds sequence but it get degraded back to set point. This is closely related to 1 above. 3) All telomeric sequence repeats from all species examined thus far appear capable of forming very stable G-quartets. Numerous studies with different sequences and various SHORT lengths (containing 1 to 4 tandem repeats - vs thousands of tandem repeats in actual telomeres) confirm that under physiological conditions, telomeric repeats can form stable G-quartet structures in vitro. In 1991, Alan M. Zahler, James R. Williamson, Thomas Cech, and David Prescott found that G-quartet DNA structures can inhibit telomerase activity - that is, telomerase cannot use such quartets as primer for extension. If telomeric sequences in vivo do form G-quartets, then it must be regulated somehow or as soon as 4 tandem repeats were produced, further extension would be inhibited since a G-quartet could form. Obviously, such early inhibition doesn't occur. Thus comes my research proposal. I seek to confirm that telomeres, in vivo, do in fact contain G-quartets (the regulation of their formation is not the subject of _this_ particular proposal). To confirm this, I intend to remove and seperate telomeric DNA from chromosomes in Oxytricha (since they contain many thousands of telomeres), treat with Proteinase K and RNAse, and check the CD on the DNA to check for G-quartet content. Another part of the study would be in S. cerevisiae in which I wish to knockout the TLC1 gene, which codes for the yeast ribonucleioprotein telomerase template component of the holoenzyme, with a version containing alterations to the template such that G-quartets could not form. If G-quartets are important for telomere length regulation, then the inability to produce G-quartets should lead to increased length of telomeres in so treated yeast. Alternatively, I could use a MoMLV vector to introduce a similarly altered telomerase template gene into a mouse cell line, overexpress it with a CMV promoter to favor mutant holoenzyme formation, and check for telomere length alterations vs G-quartet content (alternatively, I could go for a knockout). This latter (mouse) is more complicated but has the advantage to being more applicable to mammalian telomere systems. Any comments or suggestions? Have I missed something obvious that might go easier or quicker? Patrick From owner-ageing@net.bio.net Sun Apr 09 23:00:00 1995 Path: biosci!galaxy.ucr.edu!ihnp4.ucsd.edu!network.ucsd.edu!licr-user003.ucsd.edu!user From: obogler@ucsd.edu (Oliver Bogler) Newsgroups: bionet.molbio.ageing Subject: Re: Must an AGING PROCESS be universal? Date: Mon, 10 Apr 1995 15:40:27 -0700 Organization: Ludwig Institute Lines: 74 Distribution: bionet Message-ID: References: <3m63gq$482@mserv1.dl.ac.uk> NNTP-Posting-Host: licr-user003.ucsd.edu In article <3m63gq$482@mserv1.dl.ac.uk>, wrote: > In a discussion about the definition of immortality Oliver Bogler wrote: > > But to me that is no different from saying that the stem cell that divides > > at age 120 is immortal because by definition it is derived from a cell > > that was onboard at birth. You only get cells from other cells - they are > > not ever made de novo. So the experiment would be to see whether there are > > any dividing stem cells at age 120 - and that is all. > I have serious difficulty with this definition. We do not know how long an > individual stem cell lives. The parent cell may divide and then fully > differentiate, i.e. until death. The daughter cell does the same, etc. Each > individual cell may live for a few days only. Yet you call the cell immortal. What is an individual cell? Cell A divides to give cells B and C. Where is cell A now? Is it dead, just because you can not point to it? If each cell lives only a few days the whole organism will die soon. > In this definition a cell is immortal when its descendants keep multiplying. > As someone else has said, this would imply, logically, that the only immortal > cell was the first one. This argument would lead to a useless definition of the term immortal - see below. > Bacteria, which will go on multiplying when regularly placed on a new > substrate, would in this line of thinking also be called immortal, although > we know for a fact that each cell only lives for a day or two. > > Also human beings would then be immortal, since they have ever been multiplying > (with some success). This shows that the definition defies common sense. Again you reveal your confusion in terms of what 'immortality' means in the context of cellular senescence. > > I could agree with calling a cell culture immortal, but there is some hybris in > the word. Isn't it a bit exaggerated? How could we prove it? Things that > cannot be proven or disproven are outside the realm of science. The term, > therefore, is unscientific. Immortal in the normal sense means to live forever, and I agree with you this is an unscientific term. However there is a scientific definition of the immortal - which I thought we were all using. In the scientific term a cell is termed immortal if it generates a lineage of descendants that do not undergo senescence at the time when sister cell clones do. We tend to be a little sloppy, if you will, in that we call cells immortal - of course as individual cells they never are, because they need to keep dividing to be termed immortal. As soon as they divide they are gone. What is immortal is in fact the clone which they give rise to. One needs to think differently about organisms and cells. Organisms give rise to descendants without losing their identity. Therefore it is easy to see that they are all individually mortal, while their species may live much longer, or even be immortal (meaning the species lives many orders of magnitude longer than any inividual). Not so for cells. If all cells have a limited life at the time that they are generated then they wouldn't last long. If you think of an example: let us consider the first ever cell: lets call it A. It divides to make B and C.If B and C are now programmed with a finite life span, and their descendants inherit that limit then soon all the cells will be dead. (This is exactly what happens when you observe fibroblasts senesce - cells derived from the same cell stop dividing and senesce at the same time.) Since bacteria, for example have lived for millions of years, you could say that they are immortal - all the bacteria alive today are related - they all eventually come from the first bacterial cell division - they are immortal. Oliver -- Oliver Bogler obogler@ucsd.edu From owner-ageing@net.bio.net Mon Apr 10 23:00:00 1995 Path: biosci!bloom-beacon.mit.edu!grapevine.lcs.mit.edu!uhog.mit.edu!rutgers!gatech!howland.reston.ans.net!vixen.cso.uiuc.edu!news.uoregon.edu!news.xmission.com!news.cc.utah.edu!corona!patrick From: Patrick O'Neil Newsgroups: bionet.molbio.ageing Subject: Telomerase Part II Date: Mon, 10 Apr 1995 23:38:52 -0600 Organization: University Of Utah Computer Center Lines: 19 Message-ID: NNTP-Posting-Host: corona.med.utah.edu Mime-Version: 1.0 Content-Type: TEXT/PLAIN; charset=US-ASCII My proposal to examine G-quartet structures at the end of telomeres as a means of preventing further telomere elongation is a dead end. I acquired information shortly after the post that this is not a likely possibility...it appears that G-quartets involving telomere ends is more likely to be associated with synapsis during meiosis rather than a normal state of telomeric ends. Pity. With a S. cerevisiae enzyme identified that specifically cleaves G-quartet structures on a single strand 5' of the structure, and G-quartets being inhibitory to telomerase driven elongation, it looked like it could make a nice little regulatory tool. The latest poop I got from a colleague was that a crystal structure, as well as NMR data, on the 3' overhang region of human telomeres under physiological conditions was available - including bound proteins attached, forms a hairpin loop back on itself, with Hoogstein base pairings between repetitive Gs. Back to the drawing board. Though I do have another idea... Any ideas and suggestions welcome. Patrick From owner-ageing@net.bio.net Tue Apr 11 23:00:00 1995 Path: biosci!rutgers!gatech!howland.reston.ans.net!spool.mu.edu!olivea!news.bu.edu!jamie From: jamie@bu.edu (James Engert) Newsgroups: bionet.molbio.ageing Subject: Re: Must an AGING PROCESS Date: 12 Apr 1995 22:30:58 GMT Organization: Boston University Lines: 35 Distribution: world Message-ID: <3mhkb2$gnv@news.bu.edu> References: <397138810wnr@longevb.demon.co.uk> <60.762.4045.0N1D9C9C@canrem.com> NNTP-Posting-Host: acs2.bu.edu X-Newsreader: TIN [version 1.2 PL0] David Lloyd-Jones (david.lloyd-jones@canrem.com) wrote: : John@longevb.demon.co.uk asks: : : JD+In article: <3lgf2r$dui@mserv1.dl.ac.uk> : +writes: : +> There are plants (ferns and trees) that live for thousands of years. In : +> such plants, however, each dividing cell has a life which is probably : + ^^^^^^^^ : +> much shorter, similar to the situation in the bacterial colony. : +> : JD+Has anyone any hard facts on this? It looks as though this is an important : +point. : John, : : Van Doorn has just presented the hard fact, elegantly and succinctly : stated. I think it's a testimony to the Net's degradation that you : don't recognise one when you see it. : : His use of the word "probably", which you underline as though it were : something odd, simply adds to the accuracy of the whole statement. : : -dlj. : : : david.lloyd-jones@canrem.com : * 1st 1.11 #3818 * "640k should be enough for anybody" - Bill Gates, 1981. No dlj, not "something odd" but something "important as John originally said. Such an distinction is important and prevents the fact from being "hard" : but as you said net degradation. From owner-ageing@net.bio.net Wed Apr 12 23:00:00 1995 Path: biosci!TENET.EDU!dashley From: dashley@TENET.EDU (Don Ashley) Newsgroups: bionet.molbio.ageing Subject: Donahue & Life Extension Foundation Date: 13 Apr 1995 03:13:41 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 57 Sender: daemon@net.bio.net Distribution: world Message-ID: References: NNTP-Posting-Host: net.bio.net The proprietors of LEF were interviewed on Donahue Wednesday. The subject of extended lifespans was discussed with an exposure of millions. While Donahue's format is to entertain people with his insulting commentary, the topic was at least exposed to many people who have more than an infantile mind. It is doubtful that people who are already committed to encouraging research for life extension were convinced that such ambition is fruitless. Many new people are motivated. Donahue was not overtly discouraging research. His attack was on the promotion of products not approved by USFDA and sensationalistic advertising. Whatever LEF has done, legal or not, they did get the attention of millions of objective thinkers as well as millions of sheep. The idea of 120 or 150 year life spans was broadcast to the nation. That seed of thought can go a long way when promoted professionally. There's even a remote possibility that some local politician was exposed to the broadcast. That politician may be a decision maker when a credible bill is introduced for funding for research. Or maybe the politician's spouse was watching and discussed it at lunch. Attaching oneself to the cause of life extension research may carry with it a stigma of fanatacism after Donahue ridiculed the LEF proprietors. Just mentioning the idea of 150 year lifespans in social conversation brings reactions of disbelief anyway. The Donahue show and the LEF provide opportunity to move forward. The mental energy has been stimulated. Proponents of research may consider avoiding endorsements of products that violate federal law even though they look good in other countries. Patrick O'Neill has investigated telomerase and its effects on longevity/immortality. (see postings this month on this list). The research must continue. 'Immortality' definition is being clarified on this list for net readers. The general public needs something to identify with in order to get motivated. 'Senescence' is not a common word among voters. The voting public who may support funding needs to be able to relate to a professional, non-stigmatized cause. 'Life extension' now carries questionable connotation. 'Longevity' remains neutral in public emotion. 'Disease' when referring to aging process offends the scientists who are possessive of the term. The choice of correct terminology carries the vote. Using terms with negative stigma obstructs communication and support. Donahue even ridiculed cryonics when he graphically described the decapitation of someone's mother for freezing. He makes money and gets to stay on the air by using repulsive commentary. If he wasn't emotional his show would lose viewers. The challenge and the opportunity is here, this week, for the courageous to promote research for the explosion of human lifespans. From owner-ageing@net.bio.net Wed Apr 12 23:00:00 1995 Path: biosci!LAFN.ORG!ad443 From: ad443@LAFN.ORG (Ralph Kush) Newsgroups: bionet.molbio.ageing Subject: ageing Date: 13 Apr 1995 08:49:15 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 6 Sender: daemon@net.bio.net Distribution: world Message-ID: <199504121728.AA06998@lafn.org> Reply-To: ad443@lafn.org NNTP-Posting-Host: net.bio.net subscribe ageing -- ad443@lafn.org (Ralph Kush) From owner-ageing@net.bio.net Wed Apr 12 23:00:00 1995 Path: biosci!rutgers!gatech!howland.reston.ans.net!news2.near.net!cat.cis.Brown.EDU!NewsWatcher!user From: st102271 Newsgroups: bionet.molbio.ageing,sci.life-extension Subject: Re: Must an AGING PROCESS be universal? was Defining... Date: Thu, 13 Apr 1995 13:33:55 -0500 Organization: Brown University -- Providence, Rhode Island USA Lines: 7 Message-ID: References: <3ZGevA7CBh107h@chambers.ak.planet.co.nz> <3lclh2$jss@news.rain.org> NNTP-Posting-Host: 128.148.164.109 Xref: biosci bionet.molbio.ageing:1686 sci.life-extension:4710 Yes, we may all have the same biochemical pathways, but the limiting aging process may differ by individual. For instance, no one has suggested that athersclerosis works differently in different humans, but some humans genetically have different numbers of LDL receptors, etc. So the aging pathway that each individual should concentrate on may very well differ. From owner-ageing@net.bio.net Thu Apr 13 23:00:00 1995 Path: biosci!bloom-beacon.mit.edu!grapevine.lcs.mit.edu!olivea!venus.sun.com!cs.utexas.edu!news.sprintlink.net!ralph.vnet.net!johnk From: johnk@vnet.net (John Kuntze) Newsgroups: bionet.molbio.ageing Subject: GETTING OLD Date: 14 Apr 1995 21:25:48 GMT Organization: --- RETIRED --- Lines: 4 Message-ID: <3mmp8s$87o@ralph.vnet.net> NNTP-Posting-Host: johnk.vnet.net X-Newsreader: News Xpress Version 1.0 Beta #3 There was an old geezer looking at this reflection in a mirror and said, "Boy, you sure have gotten UGLY since you got old. Fortunately, you don't have to worry about that much longer, your life span is closing in on you." From owner-ageing@net.bio.net Fri Apr 14 23:00:00 1995 Path: biosci!agate!howland.reston.ans.net!news2.near.net!das-news2.harvard.edu!oitnews.harvard.edu!newsfeed.rice.edu!rice!usenet From: Mark Gardner Newsgroups: bionet.molbio.ageing Subject: 133 years old Date: 15 Apr 1995 13:21:17 GMT Organization: Rice University, Houston, Texas Lines: 13 Message-ID: <3moh8d$1jv@larry.rice.edu> NNTP-Posting-Host: pinnacle.rice.edu Does anyone have any information on the old-timer that CNN reported on this morning. There was about a five second clip "sound bite" on an old man in the middle east that supposedly was confirmed to be 133 years old. They said he was a vegetarian that smoke and drank. They had a film clip of him. He looked about 70 years old. He was puffing a sig. I am mad at CNN for only giving a taste of the story and then going on to spend the next 30 minutes with WORTHLESS sports, weather and politics. In fact I rarely watch the news anymore because it is so WORTHLESS. I would almost bet that the tobacco industry found this old guy just to combat the movement to ban tobacco - more politics. From owner-ageing@net.bio.net Sat Apr 15 23:00:00 1995 Path: biosci!agate!howland.reston.ans.net!ix.netcom.com!netnews From: H.Kugler@ix.netcom.com (Dr. Hans J. Kugler) Newsgroups: bionet.molbio.ageing Subject: Re: Telomerase - - amino acid composition??? Date: 16 Apr 1995 06:11:45 GMT Organization: Netcom Lines: 8 Distribution: world Message-ID: <3mqcf1$eq4@ixnews4.ix.netcom.com> NNTP-Posting-Host: ix-lb8-27.ix.netcom.com > We did a lit search to find the amino acid composition (not sequence) of telomerase) and couldn't find anything. Has this been done? If yes, anybody have a reference? Hans J. Kugler, PhD Editor, PREVENTIVE MEDICINE UP-DATE From owner-ageing@net.bio.net Sat Apr 15 23:00:00 1995 Path: biosci!bloom-beacon.mit.edu!gatech!howland.reston.ans.net!Germany.EU.net!EU.net!uunet!in1.uu.net!rice!usenet From: Mark Gardner Newsgroups: bionet.molbio.ageing Subject: Re: Telomerase - - amino acid composition??? Date: 16 Apr 1995 21:25:23 GMT Organization: Rice University, Houston, Texas Lines: 17 Message-ID: <3ms203$4f7@larry.rice.edu> References: <3mqcf1$eq4@ixnews4.ix.netcom.com> NNTP-Posting-Host: pinnacle.rice.edu H.Kugler@ix.netcom.com (Dr. Hans J. Kugler) wrote: > We did a lit search to find the amino acid composition (not sequence) > of telomerase) and couldn't find anything. > Has this been done? If yes, anybody have a reference? > Hans J. Kugler, PhD > Editor, PREVENTIVE MEDICINE UP-DATE There is quite a lot at this address http://aeiveos.wa.com/agethry/telomere/ From owner-ageing@net.bio.net Sun Apr 16 23:00:00 1995 Path: biosci!rutgers!gatech!howland.reston.ans.net!news.sprintlink.net!news.clark.net!rahul.net!a2i!nntp-hub2.barrnet.net!nntp-sc.barrnet.net!news.fujitsu.com!amdahl.com!borg.svpal.org!oldfogy From: oldfogy@svpal.svpal.org (Bob Christopher) Newsgroups: bionet.molbio.ageing Subject: Retirement Date: 17 Apr 1995 17:34:09 GMT Organization: Silicon Valley Public Access Link Lines: 18 Message-ID: <3mu8qh$e00@borg.svpal.org> NNTP-Posting-Host: svpal.svpal.org X-Newsreader: TIN [version 1.2 PL2] This is off the subject somewhat... But I'm trying to find a newsgroup for senior citizens. I have recently retired on a very small pension and my present area is too expensive. I'm talking $600 for a studio Apartment. I'm looking for newsgroups (any group really!) for seniors where I can discuss different areas to investigate for inexpensive living. Where I am now... I don't even have enough left for a cheap bottle of wine after I pay my rent and Utilities. Thank God my Internet server is free! Any help ad to where I can info on inexpensive areas to retire will be greatly appreciated. Bob C. (oldfogy@svpal.org) From owner-ageing@net.bio.net Sun Apr 16 23:00:00 1995 Path: biosci!rutgers!gatech!howland.reston.ans.net!news.moneng.mei.com!uwm.edu!lll-winken.llnl.gov!osi-east2.es.net!oracle.pnl.gov!mica.inel.gov!cwis.isu.edu!news.cc.utah.edu!corona!patrick From: Patrick O'Neil Newsgroups: bionet.molbio.ageing Subject: Re: Telomerase - - amino acid composition??? Date: Sun, 16 Apr 1995 16:36:49 -0600 Organization: University Of Utah Computer Center Lines: 61 Message-ID: References: <3mqcf1$eq4@ixnews4.ix.netcom.com> <3ms203$4f7@larry.rice.edu> NNTP-Posting-Host: corona.med.utah.edu Mime-Version: 1.0 Content-Type: TEXT/PLAIN; charset=US-ASCII In-Reply-To: <3ms203$4f7@larry.rice.edu> On 16 Apr 1995, Mark Gardner wrote: > H.Kugler@ix.netcom.com (Dr. Hans J. Kugler) wrote: > > > We did a lit search to find the amino acid composition (not sequence) > > of telomerase) and couldn't find anything. > > Has this been done? If yes, anybody have a reference? > > Hans J. Kugler, PhD > > Editor, PREVENTIVE MEDICINE UP-DATE > > There is quite a lot at this address > > http://aeiveos.wa.com/agethry/telomere/ > What you will find is that there are many papers dealing with telomere structure, function, and replication, but that in spite of all the research, no protein component of any telomerase has yet been able to be identified. What HAS been found is the RNA template portion of the holoenzyme both in Tetrahymena and very recently, in S. cerevisiae (called TLC1: Gottschling, D. E. and Singer, M. S. 1994. TLC1: template RNA component of Saccharomyces cerevisiae telomerase. Science 266:404-409). I have here a HUGE PILE of papers dealing with telomeres from various aspects as a result of a research proposal I needed to produce. A few of them are: 1. Zakian, V. A. and Schulz, V. P. 1994. The saccharomyces PIF1 DNA helicase inhibits telomere elongation and de novo telomere formation. Cell 76:145-155. 2. Greider, C. W. and Autexier, C. 1994. Functional reconstitution of wild-type and mutant Tetrahymena telomerase. Genes & Dev. 8:563-575. 3. Gasser, S. M. and Palladino, F. 1994. Telomere maintenance and gene repression: a common end? Curr. Opin. Cell Biol. 6:373-379. 4. Greider, C. W. 1994. Mammalian telomere dynamics: healing, fragmentation, shortening and stabilization. Curr. Opin. Gene. Dev. 4:203-211. 5. Greider C. W. and Mantell, L. L. 1994. Telomerase activity in germline and embryonic cells of Xenopus. EMBO J. 13(13):3211-3217. 6. Shore, D. 1994. RAP1: a protean regulator in yeast. TIG 10(11):408-412 **(you will find that in yeast, where many of the genes that affect telomeres are characterized, that RAP1 and its partners play a major part in several activities, including telomere regulation...it is very complex)** These are a good start, certainly, and they will point you to many more. Essentially, telomerase activity can be detected but none of the direct players other than the template for Tetrahymena and yeast telomerase are known for certain. It makes certain proposals for research rather difficult to develop without compasses to point out a direction... Patrick From owner-ageing@net.bio.net Sun Apr 16 23:00:00 1995 Path: biosci!daresbury!trane.uninett.no!nac.no!Norway.EU.net!EU.net!howland.reston.ans.net!news.moneng.mei.com!uwm.edu!msunews!netnews.upenn.edu!netaxs.com!aengel From: aengel@netaxs.com (Alan Engel) Newsgroups: bionet.molbio.ageing Subject: ERATO Osaka Symposia Date: 17 Apr 1995 16:07:55 GMT Organization: Philadelphia's Complete Internet Provider Lines: 57 Message-ID: <3mu3or$cj0@netaxs.com> NNTP-Posting-Host: unix1.netaxs.com X-Newsreader: TIN [version 1.2 PL2] The Exploratory Research for Advanced Technology (ERATO) program of the Research Development Corporation of Japan (JRDC) announces its annual Osaka Symposia. Date: Thursday, 25 May, 13:00-17:05 Place: Osaka Science & Technology Center, 8F, Main Hall Admission: Free Language: Japanese Program: Opening Address (13:300-13:45) Hiromichi Matsudiara, President, JRDC Yoshizato Morphomatrix Project (13:45-14:35) - Towards Elucidation of Cell-Matrix Interactions Involved in Organ Formation Katsutoshi Yoshizato 1. Culture of Hepatocytes with Clonal Proliferation Chise Tateno 2. Culture of Papilla Cells that Support Hair Formation Takashi Matsuzuki Hirao Active Glass Project (14:35-15:05) - Laser-Induced Electronic Structure of Non-crystalline Solids Kazuyuki Hirao Intermission and Panel Session (15:05-15:25) Fusetani Biofouling Project (15:25-16:15) - Chemical Signals Involved in Communications of Marine Organisms Nobuhiro Fusetani 1. Biology of Larval Settlement Koichiro Tsurumi 2. Bioorganic Chemistry on Settlement Signal Substances Hiroshi Hirota 3. Signal Tranduction on Larval Settlement Kiyotaka Matsumura Itaya Electrochemiscopy Project (16:15-17:05) - Electrode-Liquid Interfaces at Atomic Resolution Kingo Itaya 1. Surface Structure by Combined Ultrahigh Vacuum and Electrochemistry Taro Yamada 2. Semiconductor Surfaces at Atomic Resolution Hideki Yao Panel Session also includes the following projects: 1. Takayanagi Particle Surface Project 2. Yamamoto Behavior Genes Project 3. Takai Biotimer Project Close (17:05) From owner-ageing@net.bio.net Mon Apr 17 23:00:00 1995 Path: biosci!TENET.EDU!dashley From: dashley@TENET.EDU (Don Ashley) Newsgroups: bionet.molbio.ageing Subject: Free Internet Server? Date: 18 Apr 1995 04:53:17 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 31 Sender: daemon@net.bio.net Distribution: world Message-ID: References: <3mu8qh$e00@borg.svpal.org> NNTP-Posting-Host: net.bio.net Bob, We have several retired members and would like to know how you get free internet service. Thanks Don On 17 Apr 1995, Bob Christopher wrote: > This is off the subject somewhat... But I'm trying to find a newsgroup > for senior citizens. > > I have recently retired on a very small pension and my present area is > too expensive. I'm talking $600 for a studio Apartment. > > I'm looking for newsgroups (any group really!) for seniors where I can > discuss different areas to investigate for inexpensive living. > > Where I am now... I don't even have enough left for a cheap bottle of > wine after I pay my rent and Utilities. Thank God my Internet server is > free! > > Any help ad to where I can info on inexpensive areas to retire will be > greatly appreciated. > > Bob C. (oldfogy@svpal.org) > > > From owner-ageing@net.bio.net Mon Apr 17 23:00:00 1995 Path: biosci!bcm!cs.utexas.edu!howland.reston.ans.net!news.cac.psu.edu!news.pop.psu.edu!psuvax1!news.cc.swarthmore.edu!netnews.upenn.edu!Lehigh.EDU!Lehigh.EDU!not-for-mail From: x011@Lehigh.EDU Newsgroups: bionet.molbio.ageing Subject: another wild idea Date: 18 Apr 1995 09:10:52 -0400 Lines: 275 Message-ID: <3n0dos$1vs3@ns1.CC.Lehigh.EDU> NNTP-Posting-Host: ns1.cc.lehigh.edu Old men who marry young women live significantly longer. Old women who marry young men live significantly longer. SPECTULATION: Pheromones may be a used as a message system to order the reversal of aging. This could be check out in a nursing home with young nurses taking care of old men. Babies around old women may signal a reversal of aging. The following got me going: In article <3mtsg0$mqb@netnews.upenn.edu>, wysocki@pobox.upenn.edu (Charles J. W ysocki) writes: >OWEN MEYERS (MEYERS@MCCLB0.MED.NYU.EDU) wrote: >: A friend has made a request of me that I am ill equipped to handle. If >: anyone can be of assistance, I would appreciate it. You can e-mail all >: information to me. > >I have taken the liberty to post this response rather than a direct reply >because there is considerable misunderstanding in the popular press about >pheromones in general and especially about human chemical communication. > >: explanation about pheromones and ectohormones. Basically I need to know >: what happens to humans when we smell these scents. After we inhale, >: does this stimulus travel to our brains and then to nerve endings?, etc. > >In the original definition, a pheromone was a single chemical compound >or limited set of compounds that, when released by the sender and >detected by the recipient (of the same species), would elicit a >stereotypical response each and every time. Unfortunately, for most >pheromonal responses, each of the components of the definition have >fallen by the wayside. Even for insects, wherein much more is known >about pheromones than for mammals, the complexity is enormous. For some >responses the chemical stimulus is a bouquet, composed of a delicately >balanced mixture of many compounds. In other situations, the "pheromone" >crosses species lines. For example, the "pheromone" may be released by a >predator who is sending out a mimic-message -- the sex-attractant of the >female of the prey species. The male responds to the amorous message >only to find itself in the jaws of its prey. In other situations, there >may be considerable learning or context specificity, not at all what was >in mind when the original definition was presented. Furthermore, there >is considerable diversity in the type of message/response that can occur. > >In general there are three types of pheromones: primer, releaser and >signalling. > >i) A primer pheromone may or may not be "smelled" per se, i.e., recognized >as an odor. It induces long-term effects, typically as a result of a >neuroendocrine response. For example, there are situations where expsoure >to the chemical signals of the opposite sex will stimulate the onset of >puberty -- the exposed animal reaches puberty before the unexposed animal. >In other situations, exposure of a recently inseminated female to the >chemical signals of a strange male will induce pregnancy failure. In one >species of voles, this can take place as late as a few day away from birth >resulting in a "miscarriage." > >ii) A releaser pheromone is what people generally think of when they hear >the term pheromone. It is a chemical signal that elicits a recordable >response, e.g. sexual attraction. There are many examples of releaser >pheromones in the literature; unfortunately, the chemical identity of >most releaser pheromones in unknown. > >iii) The third, and most problematic type of pheromone, is the signalling >pheromone -- chemicals that provide information but do not necessarily >elicit a behavioral response. For example, among mammals, each individual >(including humans) has a unique odor-print that is, in part, genetically >determined by genes in the major histocompatibility complex (a set of >genes that regulates the immune response). Odor-prints allow mothers to >recognize their own baby on the day of birth and for new-borns to >recognize their mother by scent alone. Signalling pheromones also >provide information about social status, e.g., level of dominance in a >group, diet, gender, age, etc. Signalling pheromones are informational. > >Among humans, NO releaser pheromones have been identified, although there >have been comercial products that claim the contrary. There are >fragrances that possess pheromones of other mammals, e.g., a pig releaser >pheromone, androstenone or androstenol, that induces sows to assume the >mating posture if they are in heat. There are some suggestions that >humans may have primer pheromones. Females that live together tend to >syncronize their menstrual cycles. Some studies have generated evidence >that this syncrony may be based in part in chemical communication between >the females. There is yet another small group of studies to suggest that >the chemical cues from males tend to regularize the cycles of females. > >: I'm considering writing an article about men's and women's fragrances, and >: how we, as humans, are attracted to these scents. > >In the world of pheromones, many primer pheromones are detected via a >specialized structure in the nose, the vomeronasal organ. There has been >a recent resurgence of interest in this structure because of possibility >that humans may possess this chemosensory organ. Like olfaction, >sensory receptors in the nose have specialized receptor proteins on their >external membrane (in the mucus overlying the sensory sheet). These >receptor proteins are most likely analogous to neurotransmitter or >hormone receptors. When activated by a ligand, these receptors transduce >the chemical information into an electrical response that is conveyed >along the axon of the cell to the respective structure in the brain -- >the olfactory bulb for olfaction and the accessory olfactory bulb for >vomeronasal receptors. > >I am going to take this discussion one step further by including >information that I have posed in this group in the past. I do this >because of its relevance to this thread. > >--------------------old thread starts here------------ > > The terms vomeronasal organ and Jacobson's organ have been used >interchangeably; however, the homology has yet to be demonstrated. >Throughout many decades of comparative research, it became clear that some >amphibians, most reptiles, and most mammals have a vomeronasal organ >(birds lack this structure -- it is present during embryogenesis but >disappears). The problems begin to arise when descriptions of primates >became available. There is no question that New World primates have a >fully developed vomeronasal organ. Where it has been investigated, >prosimians also have a vomeronasal organ. Whether Old World primates >possess a vomeronasal organ (and hence an accessory olfactory system in >general) remains wide open for discussion. One can find as many >references to support the argument that, as adults, Old World primates >lack a vomeronasal organ as references to support the claim that they have >a vomeronasal organ (see Wysocki, C.J. 1979 Neurobehavioral evidence for >the involvement of the vomeronasal system in mammalian reproduction. >Neuroscience and Biobehavioral Reviews, 3, 301-341). If Old World >primates have a vomeronasal organ, then it is possible that humans also >have a vomeronasal organ. If Old World primates lack a vomeronasal organ >and a vomeronasal system one would be hard pressed to generate an argument >that this structure reemerged with the advent of homo sapiens. If the >former, then Jacobson's Organ may be homologous with the vomeronasal >organ, but there is much comparative work to be done to demonstrate this. > > It is true that the bipolar receptor cells of animals that have a >well-defined vomeronasal organ project to the accessory olfactory bulb. >This has NOT been demonstrated for humans or for any other Old World >primate. As a side issue, the term accessory olfactory is a misnomer. In >many instances, the accessory olfactory system, with its receptors in the >vomeronasal organ, is primary, i.e., it is the system that is critical in >response to some chemical signals, especially those that affect >reproductive physiology or behavior. > > Electrical responses, equivalent to generator potentials, have been >recorded from the human Jacobson's organ; however, one should be cautious in >interpreting the origin of these responses. Furthermore, it is possible >to generate autonomic responses from activation of free nerve endings of >the trigeminal nerve endings of the trigeminal nerve, which innervates the >vomeronasal organ. As for the reported sexual dimorphism in the >electrical response -- there could be numerous reasons, including >differences in the mucus layer. > > Another big question that remains unanswered is whether Jacobson's >Organ has a neural connection with the brain that is like that seen in >other species that possess a functional vomeronasal organ. In the latter, >there exist bipolar receptor cells whose dendrites possess putative >pheromone receptors. To my knowledge none of these have yet been cloned, >although there are numerous reports of cloned putative olfactory >receptors, e.g., > >Benarie, N. Lancet, D., Taylor, C., Khen, M., Walker, N., Ledbetter, >D.H., Carrozzo, R., Patel, K., Sheer, D., Lehrach, H. and North, M.A. >Olfactory receptor gene cluster on human chromosome 17 - possible >duplication of an ancestral receptor repertoire. Hum. Mol. Genet. >3:22-235, 1994. > >Buck, L. Identification and Analysis of a Multigene Family Encoding >Odorant Receptors - Implications for Mechanisms Underlying Olfactory >Information Processing. Chem. Senses. 18:203-208, 1993. > >Buck, L. and Axel, R. A Novel Multigene Family May Encode Odorant >Receptors. A Molecular Basis for Odor Recognition. Cell 65:175-187, >1991. > >Buck, L.B. Receptor diversity and spatial patterning in the mammalian >olfactory system. Molecular Basis of Smell and Taste Transduction. 179, >1993. > >Chess, A., Buck, L., Dowling, M.M., Axel, R. and Ngai, J. Molecular >biology of smell - expression of the multigene family encoding putative >odorant receptors. Cold Spring Harb. Symp. Quant. Biol. 57505-516: 1992. > >Lancet, D., Benarie, N., Cohen, S., Gat, U., Grossisscroff, R. Hornsaban, >S., Khen, M., Lehrach, H., Natochin, M., North, M., Seidemann, E. and >Walker, N. Olfactory receptors - transduction, diversity, human >psychophysics and genome analysis. Molecular Basis of Smell and Taste >Transduction. 179, 1993. > >Lancet, D. Grossisseroff, R., Margalit, T., Seidemann, E. and Benarie, N. >Olfaction - From Signal Transduction and Termination to Human Genome >Mapping. Chem. Sense 18:217-225, 1993. > >Margalit, T. and Lancet, D. Expression of Olfactory Receptor and >Transduction Genes During Rat Development. Brain Res. Dev. Brain Res. >73:7-16, 1993. > >Ngai, J., Dowling, M.M., Buck, L., Axel, R. and Chess, A. The Family of >Genes Encoding Odorant Receptors in the Channel Catfish. Cell. >73:657-666, 1993. > >Ressler, K.J., Sullivan, S.L. and Buck, L.B. A zonal organization of >odorant receptor gene expression in the olfactory epithelium. Cell. 73: >597-609, 1993. > >Parmentier, M., Libert, F., Schurmans, S., Schiffmann, S., Lefort, A., >Eggericks, D., Ledent, Cl, Mollereau, C., Gerard,C., Perret, J., >Grootegoed, A. and Vassart, G. Expression of Members of the Putative >Olfactory Receptor Gene Family in Mammalian Germ Cells. Nature. >355:453-455, 1992. > >Schurmans, S., Muscatelli, F., Miot, F., Mattei, M.G., Vassart, G. and >Parmentier, M. The OLFR1 gene encoding the HGMP07c putative olfactory >receptor maps to the 17p13->p12 region of the human genome and reveals an >mspi restriction fragment length polymorphism. Cytogenet.Cell.Genet. >63:200-204, 1993. > >Vanderhaeghen, P., Schurmans, S., Vassart, G. and Parmeentier, M. >Olfactory receptors are displayed on dog mature sperm cells. J.Cell.Biol. >123:1441-1452, 1993. > > Back to the bipolar receptor cell in the vomeronasal organ -- the >cell bodies of the bipolar cells are located along the medial wall of a >lumen within the vomeronasal organ (bilaterally). The axons of these >cells exit the vomeronasal organ and traverse the nasal septum, cross the >cribriform plate, bypass the main olfactory bulbs and synapse in the >accessory olfactory bulbs. It is these bipolar cells that many claim are >lacking in the human. There are two recent papers that address this >issue. The first, > >Takami, S., Getchell, M.L., Chen, Y., Montibloch, LO., Berliner, D.L., >Stensaas, L.J. and Getchell, T.V. Vomeronasal epithelial cells of the >adult human express neuron-specific molecules. Neuroreport. 4:375-378, >1993. > >purports to have found a few cells that have a bipolar appearance. The >cells did stain for some epitopes that are associated with neurons, viz., >neuron-specific enolase and PGP 9.5, but these epitopes also are found on >neuroendocrine cells. Importantly, the cells did not stain for olfactory >marker protein, which does react with bipolar cells in other species that >have been investigated. The second > >Boehm, N. and Gasser, B. Sensory receptor-like cells in the human foetal >vomeronasal organ. Neuroreport. 4:867-870, 1993. > >(since this posting, another paper has appeared -- >Boehm, B., Roos, J. and Gasser, B. Luteinizing hormone-releasing hormone >(LHRH)-expressing cells in the nasal septum of human fetuses. >Developmental Brain REsearch, 82:175-180, 1994.) > >reports the presence of bipolar cells in the early stages of fetal >development; however, staining is not found in the oldest sample, >suggesting that a vomeronasal epithelium is present during embryonic >development but regresses. > > There is considerable evidence to suggest that humans might respond >to chemical cues that are not detected as a smell or that the responses >are involuntary. Some of the most recent are those that address some of >the points raised by other contributors to this thread. They include: > >Schank, J.C. and McClintock, M.K. A Coupled-Oscillator Model of >Ovarian-Cycle Syncrony Among Female Rats. J. Theor. Biol. 157:317-362, >1992. > >Weller, A. and Weller, L. Menstrual Synchrony Between Mothers and >Daughters and Between Roommates. Physiol. Behav. 53:943-949, 1993. > >Weller, A. and Weller, L. The impact of social interaction factors on >menstrual synchrony in the workplace. Psychoneuroendocrinology. >20:21-31, 1995. > >Weller, J. and Weller, A. Human menstrual synchrony - a critical >assessment. Neurosci. Biobehav. Rev. 17:427-439, 1993. > >and earlier work referenced therein. > > >========================================================================= >Charles J. Wysocki, Ph.D. wysocki@pobox.upenn.edu >Monell Chemical Senses Center FAX: 215-898-2084 >3500 Market Street Phone: 215-898-4265 >Philadelphia, PA 19104-3308 telex: 7106700328 > From owner-ageing@net.bio.net Mon Apr 17 23:00:00 1995 Path: biosci!agate!howland.reston.ans.net!news.cac.psu.edu!news.pop.psu.edu!psuvax1!news.cc.swarthmore.edu!netnews.upenn.edu!Lehigh.EDU!Lehigh.EDU!not-for-mail From: x011@Lehigh.EDU Newsgroups: bionet.molbio.ageing Subject: Re: melatonin interactions safe? Date: 18 Apr 1995 08:58:03 -0400 Lines: 33 Message-ID: <3n0d0r$4b9o@ns1.CC.Lehigh.EDU> NNTP-Posting-Host: ns1.cc.lehigh.edu In article <3mvifj$9ih@cville-srv.wam.umd.edu>, theoblit@wam.umd.edu (Jason Tayl or) writes: > >Brian Manning Delaney (bmdelane@ellis.uchicago.edu) wrote: >: In another article, dr.ray@ix.netcom.com (Dr Ray), citing >: Skene's article, said that Prozac and other SSRIs increase >: nocturnal melatonin levels. > >: This has not been established, to the best of my knowledge. >: No consistent pattern has yet emerged from the research >: findings. It would seem sensible that SSRIs would increase >: melatonin-production (since serotonin is a precursor), but > ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ >: the evidence, so far, is lacking. > >: Actually, I think there are more studies showing no effect >: of SSRIs on mel-production than studies showing either a >: positive or a negative effect. > >: -- >: Brian M. Delaney [DO NOT cc: articles to me.] > >Hmmm. Since tryptophan is a longevity antagonist, this implies >negative feedback mechanisms at work in the hypothalamus. No? > >-- >Jason Taylor | "Doctor, don't cut so deep! > | That's the third operating table you've ruined this week!" > Excellant line of thought. I would be surprised to find out there was no negative feedback mechanisms. I keep suspecting the answer is in the pineal gland. The question is how do you turn on the repair mechanism to reverse aging. Ron Blue x011@lehigh.edu From owner-ageing@net.bio.net Mon Apr 17 23:00:00 1995 Path: biosci!agate!howland.reston.ans.net!news.cac.psu.edu!news.pop.psu.edu!psuvax1!news.cc.swarthmore.edu!netnews.upenn.edu!Lehigh.EDU!Lehigh.EDU!not-for-mail From: x011@Lehigh.EDU Newsgroups: bionet.molbio.ageing Subject: Re: Telomerase - - amino acid composition??? Date: 18 Apr 1995 08:52:21 -0400 Lines: 68 Message-ID: <3n0cm5$4njr@ns1.CC.Lehigh.EDU> NNTP-Posting-Host: ns1.cc.lehigh.edu In article , Patrick O'Neil writes: >On 16 Apr 1995, Mark Gardner wrote: >> H.Kugler@ix.netcom.com (Dr. Hans J. Kugler) wrote: >> >> > We did a lit search to find the amino acid composition (not sequence) >> > of telomerase) and couldn't find anything. >> > Has this been done? If yes, anybody have a reference? >> > Hans J. Kugler, PhD >> > Editor, PREVENTIVE MEDICINE UP-DATE >> There is quite a lot at this address >> http://aeiveos.wa.com/agethry/telomere/ >> >What you will find is that there are many papers dealing with telomere >structure, function, and replication, but that in spite of all the >research, no protein component of any telomerase has yet been able to be >identified. What HAS been found is the RNA template portion of the >holoenzyme both in Tetrahymena and very recently, in S. cerevisiae >(called TLC1: Gottschling, D. E. and Singer, M. S. 1994. TLC1: template >RNA component of Saccharomyces cerevisiae telomerase. Science 266:404-409). >I have here a HUGE PILE of papers dealing with telomeres from various >aspects as a result of a research proposal I needed to produce. A few of >them are: > >1. Zakian, V. A. and Schulz, V. P. 1994. The saccharomyces PIF1 DNA >helicase inhibits telomere elongation and de novo telomere formation. >Cell 76:145-155. > >2. Greider, C. W. and Autexier, C. 1994. Functional reconstitution of >wild-type and mutant Tetrahymena telomerase. Genes & Dev. 8:563-575. > >3. Gasser, S. M. and Palladino, F. 1994. Telomere maintenance and gene >repression: a common end? Curr. Opin. Cell Biol. 6:373-379. > >4. Greider, C. W. 1994. Mammalian telomere dynamics: healing, >fragmentation, shortening and stabilization. Curr. Opin. Gene. Dev. >4:203-211. > >5. Greider C. W. and Mantell, L. L. 1994. Telomerase activity in >germline and embryonic cells of Xenopus. EMBO J. 13(13):3211-3217. > >6. Shore, D. 1994. RAP1: a protean regulator in yeast. TIG >10(11):408-412 **(you will find that in yeast, where many of the genes >that affect telomeres are characterized, that RAP1 and its partners play >a major part in several activities, including telomere regulation...it is >very complex)** > >These are a good start, certainly, and they will point you to many more. >Essentially, telomerase activity can be detected but none of the direct >players other than the template for Tetrahymena and yeast telomerase are >known for certain. It makes certain proposals for research rather >difficult to develop without compasses to point out a direction... >Patrick Patrick has made a painfully true statement. Theory drives empirical observation. Empirical observation drives theory development. Since progress has not been as good as we like, perhaps we should open the door to a brief period of wild speculation. This might suggest to the prepared receptive mind a solution at a later date. To start the ball rolling I'll throw out a wild idea. I do not remember my source. Some type of metal was used to lock on to the tips of DNA. Sorry don't remember which one. The important thing was that the DNA would conduct electricity 10,000 times higher than expected. The current flow was speculated to be useful in predicting which DNA fragments would be connected to diseases. Such a tool may be useful in aging research and yield new facts that may generate a new theory. Ron Blue x011@lehigh.edu From owner-ageing@net.bio.net Tue Apr 18 23:00:00 1995 Path: biosci!adam.cc.sunysb.edu!news.sprintlink.net!pipex!sunsite.doc.ic.ac.uk!daresbury!not-for-mail From: Newsgroups: bionet.molbio.ageing Subject: Re: Must an AGING PROCESS be universal? Date: 19 Apr 1995 12:17:17 +0100 Lines: 158 Sender: lpddist@mserv1.dl.ac.uk Distribution: bionet Message-ID: <3n2rft$6of@mserv1.dl.ac.uk> Original-To: ageing@dl.ac.UK In a discussion about the term immortal Oliver Bogler annotated my message and wrote: > > > In a discussion about the definition of immortality Oliver Bogler wrote: > > > But to me that is no different from saying that the stem cell that divides > > > at age 120 is immortal because by definition it is derived from a cell > > > that was onboard at birth. You only get cells from other cells - they are > > > not ever made de novo. So the experiment would be to see whether there are > > > any dividing stem cells at age 120 - and that is all. > > > I have serious difficulty with this definition. We do not know how long an > > individual stem cell lives. The parent cell may divide and then fully > > differentiate, i.e. until death. The daughter cell does the same, etc. Each > > individual cell may live for a few days only. Yet you call the cell immortal. > > What is an individual cell? Cell A divides to give cells B and C. Where is > cell A now? Is it dead, just because you can not point to it? If each cell > lives only a few days the whole organism will die soon. > > > In this definition a cell is immortal when its descendants keep multiplying. > > As someone else has said, this would imply, logically, that the only immortal > > cell was the first one. > > This argument would lead to a useless definition of the term immortal - > see below. > > > Bacteria, which will go on multiplying when regularly placed on a new > > substrate, would in this line of thinking also be called immortal, although > > we know for a fact that each cell only lives for a day or two. > > > > Also human beings would then be immortal, since they have ever been > multiplying (with some success). This shows that the definition defies common sense. > > Again you reveal your confusion in terms of what 'immortality' means in > the context of cellular senescence. > > > > > I could agree with calling a cell culture immortal, but there is some > hybris in > > the word. Isn't it a bit exaggerated? How could we prove it? Things that > > cannot be proven or disproven are outside the realm of science. The term, > > therefore, is unscientific. > > Immortal in the normal sense means to live forever, and I agree with you > this is an unscientific term. However there is a scientific definition of > the immortal - which I thought we were all using. In the scientific term a > cell is termed immortal if it generates a lineage of descendants that do > not undergo senescence at the time when sister cell clones do. We tend to > be a little sloppy, if you will, in that we call cells immortal - of > course as individual cells they never are, because they need to keep > dividing to be termed immortal. As soon as they divide they are gone. What > is immortal is in fact the clone which they give rise to. > > One needs to think differently about organisms and cells. Organisms give > rise to descendants without losing their identity. Therefore it is easy to > see that they are all individually mortal, while their species may live > much longer, or even be immortal (meaning the species lives many orders of > magnitude longer than any inividual). Not so for cells. If all cells have > a limited life at the time that they are generated then they wouldn't last > long. If you think of an example: let us consider the first ever cell: > lets call it A. It divides to make B and C.If B and C are now programmed > with a finite life span, and their descendants inherit that limit then > soon all the cells will be dead. (This is exactly what happens when you > observe fibroblasts senesce - cells derived from the same cell stop > dividing and senesce at the same time.) Since bacteria, for example have > lived for millions of years, you could say that they are immortal - all > the bacteria alive today are related - they all eventually come from the > first bacterial cell division - they are immortal. > > Oliver > I am very glad that we do agree on one thing: the term immortal, in whatever context we want to use it (either referring to cells or individuals, or to cell lines) is unscientific. Cell biologist should try to avoid unscienti- fic terms. You call bacteria immortal, yet we know that they live for a few days only. It is beyond me how we could use one term for two different levels. Level one is that of the individual (cell or multicellular organism), the other the level of the cell line. Most biologists would use the term for the latter purpose only. You tell people that disscuss with you rather rapidly that they are confused. The only thing I am trying to do is to get clear definitions. So let us stay polite. As far as I can see it there is a form of circular argument in the terminology of people working with cell cultures. They established the very interesting fact that cells undergo a limited number of divisions, then stop dividing unless treated with carcinogenic agents. As cells from older individuals showed a lower number of divisions the hypothesis was put forward that a limited number of cell divisions is a main cause of ageing and death. I think this is a very plausible thought, but as far as I know there is still quite a debate whether this is true. A cell line then is called senescent when it does not show division any more, and immortalized when it goes on dividing. Here probably is the fallacy of circular reasoning. Normally, biologist would call a cell senescent when it is in a stage of differentiation leading to programmed death, this is usually long after its last division. To call a cell line senescent when it does not divide any more, while the cells are staying alive looks as if the above hypothesis is taken for a fact. Also the term immortal can then be understood: a halt to cell division is regarded as death (related to the individual the cell line was taken from), and when the cease-division is overcome it is regarded as life (even 'immortal' life). Would it not be better to use neutral terms for the stages in cell cultures like a) dividing, b) quiescent, c) nondividing, and d) carcinogenic, or any other set of terms that just describes the facts. Wouter van Doorn ATO-DLO, Wageningen, Holland > > > Return-path: > Received: from ATO4 by ATO2.ATO.AGRO.NL (PMDF V4.3-7 #7552) > id <01HP7FL4LM2800009N@ATO2.ATO.AGRO.NL>; Tue, 11 Apr 1995 08:28:01 GMT > Received: from AGRO02 by ATO.AGRO.NL (PMDF V4.3-7 #7552) > id <01HP792QKXOG0019YP@ATO.AGRO.NL>; Tue, 11 Apr 1995 05:20:03 GMT > Received: from mserv1.dl.ac.uk by AGRO.NL (PMDF V4.2-12 #4885) > id <01HP79265FSW00261T@AGRO.NL>; Tue, 11 Apr 1995 05:19:36 MET > Received: by mserv1.dl.ac.uk id DAA21592 > (8.6.10/5.3[ref postmaster@dl.ac.uk] for dl.ac.uk from server-daemon@dl.ac.uk) > ; Tue, 11 Apr 1995 03:00:33 +0100 > Received: by mserv1.dl.ac.uk id CAA20784 > (8.6.10/5.3[ref postmaster@dl.ac.uk] for dl.ac.uk from server-daemon@dl.ac.uk) > ; Tue, 11 Apr 1995 02:51:27 +0100 > Received: by mserv1.dl.ac.uk id CAA19150 > (8.6.10/5.3[ref postmaster@dl.ac.uk] for dl.ac.uk from news@dl.ac.uk); Tue, > 11 Apr 1995 02:31:46 +0100 > Resent-date: Tue, 11 Apr 1995 00:00:33 +0000 (UT) > Date: Mon, 10 Apr 1995 15:40:27 -0700 > Resent-from: server-daemon@dl.ac.uk > From: obogler@ucsd.edu (Oliver Bogler) > Subject: Re: Must an AGING PROCESS be universal? > Sender: "bionet.molbio.ageing mail newsgroup" > To: "bionet.molbio.ageing mail newsgroup" > Reply-to: obogler@ucsd.edu (Oliver Bogler) > Resent-message-id: > Message-id: <954110033.~INN-LTFa00165.bionet-news@dl.ac.uk> > X-Mailer: MXT V 12.16.1 > Content-transfer-encoding: 7BIT > Precedence: list > X-Article-Number: bionet.molbio.ageing Msg # 1396 > X-Listpath: bionet-news > Comments: List problems/queries to > Comments: To mail both the group and netnews send to (ageing@dl.ac.uk) > From owner-ageing@net.bio.net Tue Apr 18 23:00:00 1995 Path: biosci!bcm!cs.utexas.edu!howland.reston.ans.net!vixen.cso.uiuc.edu!uwm.edu!msunews!harbinger.cc.monash.edu.au!news.uwa.edu.au!cjmann From: cjmann@tartarus.uwa.edu.au (Christopher Mann) Newsgroups: bionet.molbio.ageing Subject: Organelle Nucleic Acid Stability and Ageing Date: 19 Apr 1995 10:58:59 GMT Organization: The University of Western Australia Lines: 1 Message-ID: <3n2qdj$hrn@styx.uwa.edu.au> NNTP-Posting-Host: cyllene.uwa.edu.au X-Newsreader: TIN [version 1.2 PL2] From owner-ageing@net.bio.net Wed Apr 19 23:00:00 1995 Path: biosci!rutgers!uwm.edu!msunews!harbinger.cc.monash.edu.au!news.uwa.edu.au!cjmann From: cjmann@tartarus.uwa.edu.au (Christopher Mann) Newsgroups: bionet.molbio.agei