From owner-ageing@net.bio.net Wed Jun 01 23:00:00 1994 Path: biosci!daresbury!trane.uninett.no!eunet.no!nuug!EU.net!uunet!nwnexus!flames!venezia From: venezia@zgi.com (Domenick Venezia) Newsgroups: bionet.molbio.ageing Subject: telomerase Date: 2 Jun 1994 02:42:44 GMT Organization: Northwest Nexus Inc. Lines: 35 Message-ID: <2sjgv4$g33@nwfocus.wa.com> NNTP-Posting-Host: flames.zgi.com X-Newsreader: TIN [version 1.2 PL2] Lisa Ruthig at Wistar Institute writes: >In article <2s627i$d9s@nwfocus.wa.com>, venezia@zgi.com (Domenick Venezia) >wrote: >> >> Sidney Shall says that the RNA moiety has been cloned but the protein >> moiety has not been. I'm not sure which organisms Sidney is talking about, >> but at least the yeast protein moiety has been cloned. Lundblad, V. and >> Szostak, J.W. "A Mutant with a Defect in Telomere Elongation Leads to >> Senescence in Yeast", Cell 57:633-643. Search for locus EST1 in >> PIR and/or EST1_YEAST in SWISS-PROT. The RNA moiety has been cloned from >> about 8 ciliates (Cell 67:343-353). >> >From " An Alternative Pathway for Yeast Telomerase Maintenance Rescues >ext1- Senescence," Cell 73:347-360 Lundblad and Blackburn: > >EST1 mutants show a continuous decline in telomere length and increases >in frequency of cell death and chromosome loss. "These phenotypes are >consistent with the hypothesis that the EST1 gene encodes an essential >component of the yeast telomere replication machinery, such as telomerase, >although other mechanisms for the failure to replicate telomeres are not >excluded." > > Note that they do not claim to have definitely cloned telomerase. I agree that they do not state that, and in fact in a review of the references immediately at my disposal no one in an original paper makes the statement. So I stand corrected and allow me to ammend my previous statement to state that a putative telomerase has been cloned. Domenck Venezia ZymoGenetics Seattle, WA venezia@zgi.com From owner-ageing@net.bio.net Wed Jun 01 23:00:00 1994 Path: biosci!agate!howland.reston.ans.net!pipex!uknet!daresbury!not-for-mail From: Newsgroups: bionet.molbio.ageing Subject: desirability of aging Date: 2 Jun 1994 09:34:15 +0100 Lines: 34 Sender: daemon@mserv1.dl.ac.uk Distribution: bionet Message-ID: <2sk5i7$bpf@mserv1.dl.ac.uk> Original-To: ageing@dl.ac.uk I have followed the discussion on the desirability of aging with interest, but also with some feelings of doubt. Modern societies are aging very rapidly and with aging comes the burden of chronic diseases like dementia, arthrosis etcetera. Life expectancy (LE) in the netherlands for instance is (1990) for women at birth 80.1 year, for men 73.9 year. At 65 years LE for women is 19.0 years and for men 14.4 years. At this moment about 13% of the Dutch population is over 65 years and this will expand till about 25% in 2010/2020. But if we look at how many years people can be expected to be in good health, we see something else. This measure is called Healthy Life Expectancy (HLE) or Disabillity Free Life Expectancy (DFLE) and is first developed by Sullivan in the '70's. This measure is based on the prevalence of disabilities in the population. For the Dutch population the figures are as followes: female: at birth 60.2 years; at 65 years 9.1 years male: at birth: 60.0 years; at 65 years 9.3 years We can also look at the HLP (Healthy Life Percentage), that is the percentage of the LE that can be expected to be healthy years: for women at birth: 75.1%, at 65 years of age: 48.0% for men at birth: 81.2%, at 65 years of age: 64.6%. This means for instance for women at 65 years of age in 1990, that they can expect to have more than half of their remaining life te be in poor health. Maybe we better look in ways to lower the amount of unhealthy years by prevention of chronic diseases like arthritis or Rheuma than to put a lot of money in research to expand our LE. Rom Perenboom, Leiden E-Mail: Perenboom@NIPG.TNO.NL From owner-ageing@net.bio.net Wed Jun 01 23:00:00 1994 Path: biosci!agate!howland.reston.ans.net!pipex!lyra.csx.cam.ac.uk!warwick!not-for-mail From: cuhes@csv.warwick.ac.uk (Malcolm McMahon) Newsgroups: bionet.molbio.ageing Subject: Re: desirability of aging. Date: 2 Jun 1994 10:32:10 +0100 Organization: University of Warwick, Coventry, UK Lines: 40 Message-ID: <2sk8uq$rlt@crocus.csv.warwick.ac.uk> References: <15498.9405270859@mailer.leeds.ac.uk> <2s62t5$65c@search01.news.aol.com> <2s7uop$p5n@acmex.gatech.edu> NNTP-Posting-Host: crocus-fddi.csv.warwick.ac.uk Mime-Version: 1.0 Content-Type: text/plain; charset=US-ASCII Content-Transfer-Encoding: 7bit In article <2s7uop$p5n@acmex.gatech.edu>, > >The initial aspects of a means to stop aging if it were cheap enough to be >generally available would be devastating to our society. One third of our >society would be back at work (as they would be essentially very knowledgeable >twenty year olds) and the birth rate would not slow down significantly. This >cannot help but to generate a lot of war and other craziness as the >population increases. > I'd have said that the effects of a cure for ageing that was _not_ cheap enought to be generally available, or which a clique tried to keep to themselves would be a great deal more devestating. People would rightly regard anyone that came between them and the cure as threatening their life. When you think about the motivations for having children I would guess that the birth rate _would_ slow significatly. People would feel less urgency about having kids. At the same time there seems no reason why a cure for aging should affect the menopause. As I understand it a woman simply runs out of eggs. The point is, I think, that when you consider the population equations the life-expectancy is only, at most, a multiplicative factor while the birth rate is an exponential factor. I would presume that quite a modest decline in birth rate would compensate for a large change in longevity. >The way I hope aging research progresses is for it to reduce old age >infirmity (as it is doing now), but still keep the limit at ~85 years. As >our society progresses, the age limit will hopefully move upwards with >the onset of the disease getting closer and closer to the maximum age limit. >Basically, people staying young until they die. I wonder how it would feel to be coming up to the age limit in perfect health and with a clear mind. Malcolm From owner-ageing@net.bio.net Wed Jun 01 23:00:00 1994 Path: biosci!agate!howland.reston.ans.net!pipex!warwick!not-for-mail From: cuhes@csv.warwick.ac.uk (Malcolm McMahon) Newsgroups: bionet.molbio.ageing Subject: Re: telomeres Date: 2 Jun 1994 10:40:19 +0100 Organization: University of Warwick, Coventry, UK Lines: 17 Message-ID: <2sk9e3$st9@crocus.csv.warwick.ac.uk> References: <68388@sdcc12.ucsd.edu> <2s8gsq$jql@search01.news.aol.com> NNTP-Posting-Host: crocus-fddi.csv.warwick.ac.uk Mime-Version: 1.0 Content-Type: text/plain; charset=US-ASCII Content-Transfer-Encoding: 7bit In article , jabowery@netcom.com (Jim Bowery) writes: >abubu@aol.com (ABUBU) writes: > >The basic answer is that the "unit of selection" is not the >individual, but the "gene". Genes are already "immortal" so >there is no inherent selective advantage for increasing the longevity >of the bodies carrying them. But why wouldn't an older, more experienced animal be a better parent? In wild animals, who generally die of unnatural causes, the effect would be marginal but even a marginal postive is selected for by evolution if there isn't a delitorious side-effect. Malcolm From owner-ageing@net.bio.net Wed Jun 01 23:00:00 1994 Path: biosci!agate!howland.reston.ans.net!pipex!lyra.csx.cam.ac.uk!warwick!not-for-mail From: cuhes@csv.warwick.ac.uk (Malcolm McMahon) Newsgroups: bionet.molbio.ageing Subject: Re: telomeres Date: 2 Jun 1994 10:53:17 +0100 Organization: University of Warwick, Coventry, UK Lines: 32 Message-ID: <2ska6d$1b9@crocus.csv.warwick.ac.uk> References: <9405190315.AA24155@pclsp2> <2s2c6h$hj1@crocus.csv.warwick.ac.uk> <68388@sdcc12.ucsd.edu> NNTP-Posting-Host: crocus-fddi.csv.warwick.ac.uk Mime-Version: 1.0 Content-Type: text/plain; charset=US-ASCII Content-Transfer-Encoding: 7bit In article <68388@sdcc12.ucsd.edu>, wsun@jeeves.ucsd.edu (Fiberman) writes: >In article <2s2c6h$hj1@crocus.csv.warwick.ac.uk> cuhes@csv.warwick.ac.uk (Malcolm McMahon) writes: > >>The death clock argument is the first suggested mechanism of aging that >>has ever made sense to me because it explains why there are no imortal >>mutants - they die of cancer before we notice they are immortal. > >But using the same argument as above. There must be a way to >prevent cancer in old age. A single cell can develop into an >organism without any problems, why would an adult organism >eventually develop cancer? > The death clock _is_ such a protective mechanism. It presents a second hurdle that a mutation must overcome to be a "successful" cancer. This is because a cancer that does no overcome the death clock will quickly use up its alloted number of divisions. A single cell does not always make it to an adult organism. I think that, approximately, any given cell has a certain chance of becoming cancerous in a given time regardless of age etc. If you take the rough approximation that, with the ageing clock, the mutation has to overcome two successive obstacles to become a maligancy: the ordinary controls and the death clock and guess that the chances of overcoming each are about the same then, were the death clock stopped, the odds against you getting a malignancy in any time period would presumably be reduced to the square root. Supposing (another guesstimate) the chances of contracting a malignancy in any year are 200 to 1 against then removing the death clock would make them 14 to 1. If this is even approximately true it's no wonder we don't see imortal mutants. Malcolm From owner-ageing@net.bio.net Wed Jun 01 23:00:00 1994 Path: biosci!daresbury!trane.uninett.no!eunet.no!nuug!EU.net!uunet!nwnexus!flames!venezia From: venezia@zgi.com (Domenick Venezia) Newsgroups: bionet.molbio.ageing Subject: Re: How evolution works Date: 2 Jun 1994 23:34:34 GMT Organization: Northwest Nexus Inc. Lines: 23 Message-ID: <2slqaa$dio@nwfocus.wa.com> References: <1994Jun2.145209.16926@emr1.emr.ca> NNTP-Posting-Host: flames.zgi.com X-Newsreader: TIN [version 1.2 PL2] Cathy Woodgold (woodgold@seismo.emr.ca) wrote: . . . : helps a lot too.) Anyway, this is one way that bad mutations are weeded out : in the human species; that method can't be used by an individual who is : living thousands of years! Correct me if I misunderstood, but what you are saying is that I should consent to die for the betterment of human evolution? Sorry, I'm a fairly altruistic guy, but my altruism has to be based on something a little more substantial. I mean, I have and would risk my life for someone or something, but I can guarantee I would not happy lie down in my grave for the sake of something as nebulous and ill defined as "human evolution". If the betterment of human evolution is your goal then you should have second thoughts about most of the field of medicine, after all death from disease and injury is "How Evolution Works" too. One last thought is that human evolution no longer works only on the level of the organism but also on the levels of technology and culture, so you can evolve a "better" human by affecting the organism and/or the culture and technology. Domenick Venezia ZymoGenetics, Seattle, WA venezia@zgi.com From owner-ageing@net.bio.net Wed Jun 01 23:00:00 1994 Path: biosci!daresbury!not-for-mail From: Kurt Schaudt Newsgroups: bionet.molbio.ageing Subject: Re: telomeres Date: 2 Jun 1994 21:45:34 +0100 Lines: 59 Sender: daemon@mserv1.dl.ac.uk Distribution: bionet Message-ID: <2slgde$knr@mserv1.dl.ac.uk> Original-To: Ageing discussion group On 28 May 1994, ABUBU wrote: > In article <68388@sdcc12.ucsd.edu>, wsun@jeeves.ucsd.edu (Fiberman) > writes: > > >There's no selection for longevity genes since as long as > >an organsim reaches the reproductive age, it has survived well > >in the evolutionary sense. > > I have heard this several times, but I do not see why. Wouldn't an > organism that stayed as a reproductive adult permanently have a great > advantage? It could have ten times (just to pick a number) as many > offspring as another organism that aged normally. It would also have > a better chance of staying alive, and rearing it's young by virtue of > experience. I am not persuaded by this argument. If the longevity genes of the organism would be not dominant it would not render his longevity to its offspring - except it would meet a partner with the same longevity genes. I think that this is extremely unlikely because such genomic longevity structure must be very complex and would affect multiple genes. I don't think that there are any genomic programs responsible for promoting ageing (telomere shortening seems not to affect our real lifespans) but there must be programs for counteracting ageing processes (accumulated poisoning, damages by oxidants and so on). As long as ageing processes are hindering the organism from reproduction there is a most strong evolutionary pressure for developing and enhancing genomic programs that counteract ageing. When lifespan is sufficient to have enough offspring this pressure vanishes totally. From this angle the lack of organisms enjoying longevity is not surprising at all: When (in early times) lifespan doesn't suffice to give all individuals the chance to reproduce (because many die before reaching fertility), only those with good "longevity" genes will meet others for reproduction who necessarily also have such benefical genes. So enhancement of the longevity apparatus is warranted even under hard conditions (meeting of a partner with properly fitting genes) - if fitting fails, descendants will not be able to reproduce. This pitiless pressure vanishes when the organisms has enhanced his lifespan sufficiently to allow all individuals to reproduce, so further enhancements come to a standstill. Besides this complexity (and number of responsible genes) will greatly be enhanced with longer lifespans. Eg mechanisms for counteracting oxidation processes in the lense of the eye must be VERY MUCH more perfect when they are capable to protect it, say, 60 years from cataract (man) than those protecting only, say, 5 years (dog). So meeting of partners with corrosponding enhanced genes counteracting ageing processes will become more and more unlikely. Kurt Schaudt From owner-ageing@net.bio.net Wed Jun 01 23:00:00 1994 Path: biosci!daresbury!doc.ic.ac.uk!warwick!not-for-mail From: cuhes@csv.warwick.ac.uk (Malcolm McMahon) Newsgroups: bionet.molbio.ageing Subject: Re: telomerase Date: 2 Jun 1994 21:20:35 +0100 Organization: University of Warwick, Coventry, UK Lines: 14 Message-ID: <2sleuj$4po@crocus.csv.warwick.ac.uk> References: <9406021636.AA27576@pclsp2> Reply-To: malcolm@geog.leeds.ac.uk NNTP-Posting-Host: crocus-fddi.csv.warwick.ac.uk Mime-Version: 1.0 Content-Type: text/plain; charset=US-ASCII Content-Transfer-Encoding: 7bit In article <9406021636.AA27576@pclsp2>, vinz@PCLSP2.KUICR.KYOTO-U.AC.JP (Vincenzo Nardi-Dei) writes: > > >This, being maybe thrue, does not exclude the importance of the second >principle of the thermodinamic in the process of aging. > I don't think that thermodynamics is a lot of use in far from equilibrium stiuations like life. If they were the laws of thermodynamics would have destroyed all life before it got started. Malcolm From owner-ageing@net.bio.net Wed Jun 01 23:00:00 1994 Path: biosci!daresbury!doc.ic.ac.uk!warwick!not-for-mail From: cuhes@csv.warwick.ac.uk (Malcolm McMahon) Newsgroups: bionet.molbio.ageing Subject: Re: telomeres Date: 2 Jun 1994 21:15:05 +0100 Organization: University of Warwick, Coventry, UK Lines: 20 Message-ID: <2slek9$jko@crocus.csv.warwick.ac.uk> References: <68388@sdcc12.ucsd.edu> <2sk9e3$st9@crocus.csv.warwick.ac.uk> Reply-To: malcolm@geog.leeds.ac.uk NNTP-Posting-Host: crocus-fddi.csv.warwick.ac.uk Mime-Version: 1.0 Content-Type: text/plain; charset=US-ASCII Content-Transfer-Encoding: 7bit In article , jabowery@netcom.com (Jim Bowery) writes: > >Clearly in animals where learning is critical, as it is in humans >in a technological civilization, we should expect to see strong selective >pressures toward life-long learning, prolonged fertility in women >and general longevity. You don't need a technological civilisation. As soon as you have language you can gain an evolutionary advantage by instructing your grandchildren. In reallity the technological civilisation may _reduce_ the advantage by collectivising the instructor role. But what I'm saying is that even in animals with little behavioural plasiticity as adults and a high casualty rate longevity is _still_ an advantage, albeit a marginal one and senescence would be evolved out unless longevity was strongly tied to some delitorious effect in young life. Malcolm From owner-ageing@net.bio.net Wed Jun 01 23:00:00 1994 Newsgroups: bionet.molbio.ageing Path: biosci!agate!overload.lbl.gov!dog.ee.lbl.gov!ihnp4.ucsd.edu!library.ucla.edu!csulb.edu!csus.edu!netcom.com!jabowery From: jabowery@netcom.com (Jim Bowery) Subject: Re: telomeres Message-ID: Organization: NETCOM On-line Communication Services (408 261-4700 guest) References: <68388@sdcc12.ucsd.edu> <2s8gsq$jql@search01.news.aol.com> <2sk9e3$st9@crocus.csv.warwick.ac.uk> Date: Thu, 2 Jun 1994 17:37:05 GMT Lines: 29 cuhes@csv.warwick.ac.uk (Malcolm McMahon) writes: > In article , > jabowery@netcom.com (Jim Bowery) writes: > >abubu@aol.com (ABUBU) writes: > > > >The basic answer is that the "unit of selection" is not the > >individual, but the "gene". Genes are already "immortal" so > >there is no inherent selective advantage for increasing the longevity > >of the bodies carrying them. > > But why wouldn't an older, more experienced animal be a better parent? > In wild animals, who generally die of unnatural causes, the effect > would be marginal but even a marginal postive is selected for by > evolution if there isn't a delitorious side-effect. Clearly in animals where learning is critical, as it is in humans in a technological civilization, we should expect to see strong selective pressures toward life-long learning, prolonged fertility in women and general longevity. However, technological civilization is brand new in evolutionary terms. To first order, we can view the genetic algorithms that have evolved as working to overcome natural deterioration by restarting the execution of the programs via reproduction. There just wasn't any big advantage to longevity. There is now. -- The promotion of politics exterminates apolitical genes in the population. The promotion of frontiers gives apolitical genes a route to survival. From owner-ageing@net.bio.net Wed Jun 01 23:00:00 1994 Path: biosci!RESUNIX.RI.SICKKIDS.ON.CA!shah From: shah@RESUNIX.RI.SICKKIDS.ON.CA Newsgroups: bionet.molbio.ageing Subject: (none) Date: 2 Jun 1994 10:27:08 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 17 Sender: daemon@net.bio.net Distribution: world Message-ID: <9406021713.AA15767@resunix.ri.sickkids.on.ca> NNTP-Posting-Host: net.bio.net I have a technical question: Are there any assays that can be done on tissue thin sections for distinguishing between apoptosis and necrosis? I know there is a method available that probes for generation of DNA 3'-ends by using terminal transferase. Are there other methods available. For example antibodie to proteins that are preferentially induced during apoptosis. I also have a question about quiescent (G0 phase) cells. Are there any general markers that could be used with all cell types for in situ hybridization? Thank you for cosidering my questions Sherry shah@resunix.ri.sickkids.on.ca From owner-ageing@net.bio.net Wed Jun 01 23:00:00 1994 Path: biosci!PCLSP2.KUICR.KYOTO-U.AC.JP!vinz From: vinz@PCLSP2.KUICR.KYOTO-U.AC.JP (Vincenzo Nardi-Dei) Newsgroups: bionet.molbio.ageing Subject: Re:telomerase Date: 2 Jun 1994 09:34:13 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 13 Sender: daemon@net.bio.net Distribution: world Message-ID: <9406021636.AA27576@pclsp2> NNTP-Posting-Host: net.bio.net >The idea is that the death clock is a second line of defence against cancer. >That to be a "success" and cancerous mutation must overcome both the normal >controls on growth and the death clock. This would enourmously decrease the >likelyhood of any given mutation being dangerous. > >Malcom This, being maybe thrue, does not exclude the importance of the second principle of the thermodinamic in the process of aging. -- Vincenzo From owner-ageing@net.bio.net Wed Jun 01 23:00:00 1994 Newsgroups: bionet.molbio.ageing Path: biosci!agate!howland.reston.ans.net!spool.mu.edu!torn!nott!emr1!news From: woodgold@seismo.emr.ca (Cathy Woodgold) Subject: How evolution works Message-ID: <1994Jun2.145209.16926@emr1.emr.ca> Sender: news@emr1.emr.ca Nntp-Posting-Host: saw19.seismo.emr.ca Reply-To: woodgold@seismo.emr.ca Organization: Geological Survey of Canada Date: Thu, 2 Jun 1994 14:52:09 GMT Lines: 33 I'd like to add some thoughts to the discussions that have been happening under the thread "telomeres". What happens to an organism after menopause DOES affect its evolution. In the extreme case, if a woman died immediately after giving birth to her last child, that child's chances of survival ... and of success ... would be diminished. Children do not look after themselves; their success is contributed to by parents, grandparents, aunts, great-aunts, uncles, great-uncles, etc., unrelated neighbours, etc. When a person stays alive beyond the child-bearing years, that person usually continues to contribute to society and thus contributes to the success of their own genes as represented in their grandchildren, grandneices and nephews, etc. That's one reason why humans have an instinctive desire to contribute to the community. Humans did not evolve as individuals, but as communities (almost like a multi-celled organism, wherin the cells are people!) Now we can use that instinctive desire to contribute, and focus it on a global perspective and the ultimate survival of the ecological planet and the whole species of humans and other life forms too. Many miscarriages occur, often before the woman knows she's pregnant. We don't really know the miscarriage rate because it often happens in the first few weeks and is not detectable. The miscarriage rate can be decreased a lot by both parents using excellent nutrition (mega-vitamins, anti-oxidants, etc.) in the three months before conception. Apparently the miscarriages are usually caused by mutations, which of course are almost always bad rather than good. (Excellent nutrition during the pregnancy helps a lot too.) Anyway, this is one way that bad mutations are weeded out in the human species; that method can't be used by an individual who is living thousands of years! Cathy TISSATAAFL Standard disclaimer From owner-ageing@net.bio.net Wed Jun 01 23:00:00 1994 Path: biosci!agate!howland.reston.ans.net!cs.utexas.edu!swrinde!pipex!warwick!not-for-mail From: cuhes@csv.warwick.ac.uk (Malcolm McMahon) Newsgroups: bionet.molbio.ageing Subject: Re: telomeres Date: 2 Jun 1994 10:56:59 +0100 Organization: University of Warwick, Coventry, UK Lines: 20 Message-ID: <2skadb$1kc@crocus.csv.warwick.ac.uk> References: <9405301043.AA17560@pclsp2> NNTP-Posting-Host: crocus-fddi.csv.warwick.ac.uk Mime-Version: 1.0 Content-Type: text/plain; charset=US-ASCII Content-Transfer-Encoding: 7bit In article <9405301043.AA17560@pclsp2>, vinz@PCLSP2.KUICR.KYOTO-U.AC.JP (Vincenzo Nardi-Dei) writes: > >Normal cells, should not develop in cancer-like form even when >their clock is not terminated; cells are inhibited in the growth >by the contact with the surrounding cells. This contact makes the cell >to "understand" its position and role in the organism. When for some >mutation the information on the contact inhibition is lost in the >cell, it could become cancer-like. > The idea is that the death clock is a second line of defence against cancer. That to be a "success" and cancerous mutation must overcome both the normal controls on growth and the death clock. This would enourmously decrease the likelyhood of any given mutation being dangerous. Malcolm > From owner-ageing@net.bio.net Thu Jun 02 23:00:00 1994 Newsgroups: bionet.molbio.ageing Path: biosci!agate!howland.reston.ans.net!spool.mu.edu!torn!nott!emr1!news From: woodgold@seismo.emr.ca (Cathy Woodgold) Subject: Re: Evolution Message-ID: <1994Jun3.141405.11149@emr1.emr.ca> Sender: news@emr1.emr.ca Nntp-Posting-Host: saw19.seismo.emr.ca Reply-To: woodgold@seismo.emr.ca Organization: Geological Survey of Canada References: Date: Fri, 3 Jun 1994 14:14:05 GMT Lines: 31 In article qo@netcom.com, jabowery@netcom.com (Jim Bowery) writes: > Clearly in animals where learning is critical, as it is in humans > in a technological civilization, we should expect to see strong selective > pressures toward life-long learning, prolonged fertility in women > and general longevity. However, technological civilization is brand > new in evolutionary terms. To first order, we can view the genetic > algorithms that have evolved as working to overcome natural > deterioration by restarting the execution of the programs via > reproduction. There just wasn't any big advantage to longevity. > > There is now. > Technological society is NOT brand new! Of course, our current style of technology is brand new. But technology such as flint arrowheads has been around for a long time (millions of years?). Even agriculture has been around for thousands of years, long enough to affect traits that evolve quickly. Humans have lived in societies for millions of years, and longevity (even after the reproductive years end) has had advantages throughout that time. I'm thinking about Inuit who used to commit suicide when they got old so they wouldn't be a burden on their communities. Evolutionarily, the most advantageous thing (for animals who live in communities, as humans do) would be to live a fairly long time and then die off suddenly, before inevitable deterioration makes one a drain on the community. This could be a reason for a death clock to evolve (though I don't think this applies to fruit flies! unless older flies would contribute gametes with too many mutations). Cathy TISSATAAFL From owner-ageing@net.bio.net Sat Jun 04 23:00:00 1994 Path: biosci!agate!howland.reston.ans.net!wupost!bcm!mbcr.bcm.tmc.edu!th035681 From: th035681@mbcr.bcm.tmc.edu (Timothy R. Hughes) Newsgroups: bionet.molbio.ageing Subject: FAQ Date: 5 Jun 1994 15:02:35 GMT Organization: Baylor College of Medicine, Houston, Tx Lines: 554 Distribution: world Message-ID: <2sspeb$in1@gazette.bcm.tmc.edu> NNTP-Posting-Host: mbcr.bcm.tmc.edu The purpose of this FAQ is to address Frequently Asked Questions on the bionet.molbio.ageing newsgroup. If you have any thoughts or suggestions, or would like to see any additional topics or specific publications included, please email me at: th035681@mbcr.bcm.tmc.edu Contents include: 1.) brief descriptions of topics generally encompassed, in order to indicate what's going on in general; and 2.) a few references, reviews and/or recent publications regarding topics in aging research. Thanks, -- Tim Hughes ======================================================================= I. Definition of Aging A. Senescence - Senescence refers to intrinsic adverse changes during aging in an organism. Strictly this is manifest as an increasing likelihood of death as a function of time, measured either from birth or from some developmental stage. [Also, strictly the term "senescence" should be used instead of "aging" in this FAQ but I haven't bothered.] Cell senescence refers to the limited proliferative capacity of cultured somatic cells (see below). 1. Gompertz Curve: A mathematical function called the "Gompertz curve" can be derived to describe expected mortality statistics for a population of organisms whose probability of death increases as a function of time. Many populations (including humans) demonstrate a survival curve which can be fit closely by a Gompertz curve. A critical parameter in the Gompertz expression is the MRDT (mortalitay rate doubling time) which is considered the index of how fast organisms in the population senesce, and it has been suggested that in scientific studies true slowing of the aging process occurs only when the MRDT increases, regardless of other aging parameters (i.e., mean, mode, maximum lifespan). General references on the study of aging: Finch, C. E. 1991. Longevity, Senescence, and the Genome. Univ. Chicago Press. 843 pages including references. Martin, George R. et al. 1993. Aging - Causes and Defenses. Annu. Rev. Med. 44:419-29. A quick overview, not entirely comprehensive but easy reading. Kirkwood, T.B.L. and Cremer, T. Cytogerontology Since 1881: A Reappraisal of August Weismann and a Review of Modern Progress. Human Genetics (1982) 60:101-121. A historical review of aging theories and arguments. II. Theories and evidence regarding the aging of multicellular organisms A. General Arguments. Population genetics [something I know little about] argues that no genetic trait which is detrimental late in life would be selected for, so no genes can survive throughout a population whose sole function is to cause senescence. The remaining possibilites are as follows: 1. Antagonistic Plieotropy: It is possible for genes which are benefical or necessary in youth or in the short term to be detrimental in the long term. An example is the cytochrome oxidase, a metabolic enzyme [detoxifant, I think] which is responsible for the initial step in transforming a number of dietary compounds into mutagenic agents. References: Aeschbacher, H-U. and Turesky, R.J. (1991) Mammalian cell mutagenicity and metabolism of heterocyclic aromatic amines. Mutation Research, 256:235-250. 2. Longevity Assurance Genes: It is also possible that genes which are designed to protect us from detriment be finite in capacity, as no selection may exist for alleles which protect for longer than the lifetime. [Example: genes involved in DNA damage control in somatic tissues.] B. Disposable Soma Theory: It has been suggested that the optimal allocation of energy for an organism which reproduces repeatedly is to invest no more energy in somatic maintenance than is necessary to ensure reproduction. [The original idea, I believe, referred primarily to DNA damage.] [Also, this argument seems unlikely to me to apply to humans. My understanding is that we consume 40% of our resting energy on brain activity, and about 30% of all ATP generated on maintaining transmembrane potentials (from which many cellular processes are driven, I'm not sure how much of that is converted into work and how much is lost by diffusion) and maintain a fairly warm body temperature. This suggests to me that energy conservation is not a significant selective advantage for mammals and humans in particular.] C. Somatic Mutation Hypothesis. DNA is inherently unstable and is susceptible to numerous modification and damaging agents. As genetic material it requires constant maintenance. One of the original ideas about the aging process is that the accumulation of somatic mutations throughout the lifespan is responsible for dysfunction of cells and consequently of organs and individuals. This has fallen out of favor as a mechanism for aging since DNA damage would be expected to be fairly random, and aging is largely consistent over a population. 2. free radicals: Reactive oxygen species are produced by mitochondria in oxidative phosphorylation, the biochemical pathway that allows us to utilize oxygen in energy production [conversion, rather]. Free radical species can also be produced by ionozing radiation. Free radicals can modify/damage a wide range of cellular molecules including DNA, lipids and proteins (see below). 2. carcinogens and mutagens: 3. cancer: 4. mitochondrial DNA damage: Mitochondria contain a small genome which due to its proximity to oxidative phosphorylation activity is more susceptible to oxidation than the nuclear DNA. Human mtDNA is 16.6 kb and encodes a small portion of the peptides involved in oxidative phosphorylation and also the rRNAs and tRNAs needed to translate these genes. It has been observed that the mutation rate of mtDNA is higher than that of the nuclear DNA, and also that there is a decline in oxidative phosphorylation activity in some tissues with age. Mitochondrial genetics is complex due to interaction with nuclear genes, predominant maternal inheritance, and the possibility that not all mitochondria in a cell need to be genetically identical. Nonetheless a number of genetic diseases are linked to mtDNA, and that mutations in nuclear genes can adversely affect mtDNA and/or oxidative phosphorylation. It has been proposed that accumulated mtDNA damage is a mechanism in aging, and that mitochondria with genomic deletions would be enriched due to a replicative advantage. [As with any theory involving genomic instability, one must reconcile the fact that babies are inevitably born young. In this case the question is: how do babies escape getting mom's 20-40 year old mitochondria?] References: Wallace, D.C. (1992) Mitochondrial Genetics: A Paradigm for Aging and Degenerative Diseases? Science 256:628-632 (May 1 1992). D. Endocrine cascade E. Cell Senescence. A number of types of human cells will undergo less than about 100 divisions when cultured (grown in a dish or flask), at which point the cells adopt a distinctive appearance and will not divide any further. As stimulus to divide in mammalian tissues consists mainly of signaling factors it has been argued that senescence is a tissue culture artifact due to improper or inadequate signaling or an adaptive tolerance to signals. In large enough sample sizes, however, an inverse correlation between number of divisions obtained and age of donor is observed, and there also exists a rough correlation between species lifespan and number of divisions obtained. Furthermore cells from individuals with Werner's syndrome (premature aging) have a reduced proliferative capacity. It has been proposed that cell senescence occurs in vivo and could be responsible for loss of homeostasis in tissues of the elderly. Cells which senesce in culture include fibroblasts, lymphocytes, various epithelial cells, and adrenocortical cells. Tumor cells do not senesce in culture and it has also been proposed that senescence acts as a tumor-control mechanism by providing an additional hurdle for growth-errant cells. It is important to note that no direct evidence for cell senescence occuring in vivo has yet been obtained. References: Warner, H.R. et al. (1992) Control of Cell Proliferation in Senescent Cells. Journal of Gerontology 47(6):B185-B189. 1. DNA synthesis inhibition In an expression screen for cDNAs (expressed genes) in senescent cells which could inhibit DNA synthesis in "young" cells, the SDI-1 gene was cloned and found to be significantly up-regulated in senescent cells compered with their young counterparts. The gene was also cloned by two other groups simultaneously using completely different methods, and is thought to be the primary element responsible for p53-dependent cell-cycle arrest. References: Hunter, Tony (1993) Braking the cycle (minireview). Cell 75:839-841 (Dec 3 '93). 2. complementation studies: Cultured cells can be fused to one another and genetic properties analyzed in a manner analagous to yeast mating. Early cell fusion experiments clearly illustrated that senescence was a dominant trait in fused cultured cells (i.e. fusions of young to senescent are senescent; immortal to senescent are senescent.) This suggested that element(s) were missing from immortal cells which could be provided by senescent cells. To determine if immortal cells were all lacking the same thing or had different deletions, various immortal cells were fused, and it was found that some complemented (rescued) each other. In a specific case, a single inserted chromosome was sufficient to restore senescence. These complementation studies have recently been challenged, with apparently different results obtained using somewhat different methods. References: Pereira-Smith, O.M. & Smith, J.R. (1988) Genetic analysis of indefinite division in human cells: Identification of four complementation groups. PNAS 85:6042-6046. Ning, Y. et.al. (1991) Genetic analysis of indefinite division in human cells: Evidence for a cell-senescence-related gene(s) on human chromosome 4. PNAS 88:5635-5639. Ryan, P.A. et al (1994) Failure of Infinite Life span human cells from different immortality complementation groups to yield finite life span hybrids. J. Cell. Phys. (in press) 2. vs. DNA damage: [The fact that senescence is a dominant property suggests that DNA damage is not responsible for the senescence phenomenon. If senescent cells had lost a function that immortal cells retained, then immortality would be dominant. It seems unlikely that senescence would be due to a gain of function mutation in all senescent cells simultaneously. If immortality were due primarily to a gain of function mutation not present in senescent cells, again immortality would be expected to dominate. The remaining possibility then is that immortality is due to a loss of function, and that senescent cells have retained the normal genotype.] 3. telomere shortening: It was originally observed by Crick around 1960 (I think) that the DNA replication machinery, which can only synthesize in one direction, would always leave a little bit of unreplicated DNA on the lagging strand at the telomere (end of the chromosome). Proteins were identified which could extend telomeres, which have a special sequence. It is now well established that human telomeres get shorter on average as a function of age, that they are elongated in sperm cells, that as cells senesce in culture their telomeres shorten with a striking uniformity. It has been proposed that telomere shortening is responsible for cell senescence and hence is involved in the aging process, but no causal role has emerged. Evidence against the telomere hypothesis: Telomere shortening in yeast leads to cell death, not the phenotype seen in mammalian cell senescence; Mouse telomeres are up to ten times as long as human telomeres and do not shorten over the lifetime, and yet mouse cells senesce faster that human cells in culture. References: Kipling, D. & Cooke, H.J. (1990) Hypervariable ultra-long telomeres in mice. Nature 347:400-402. Lundblad, V. & Szostak, J. W. (1989) A Mutant with a Defect in Telomere Elongation Leads to Senescence in Yeast. Cell 57:633-643. Allsopp, R.C. et al. (1992) Telomere Length predicts replicative capacity of human fibroblasts. PNAS 89(21):10114-8. F. Apoptosis Apoptosis is a cell death mechanism involving activation of specific genes and a morphologically distinct, controlled self-destruction program. It is generally a response to a signal or stress rather than acute trauma. Apoptosis clearly plays a role in development, and it appears that random loss of cells in aging (apparently common in central nervous system and muscle) may result from random activation a cell death program. References: Lockshin, R.A. & Zakeri, Z.F. (1990) Programmed Cell Death: New Thoughts and Relevance to Aging. J. of Gerontology 45(5):B135-140. G. Oxidative Stress Hypothesis The free radical theory has given rise to the "oxidative stress hypothesis", which asserts that modification and damage to cellular molecules by free radicals is capable of altering "genetic programs" and disrupting cell function, thereby contributing to aging regardless of DNA damage. This model draws support from observations that (1) the free hydroxyl radical can clearly contribute to biochemical pathways producing not only damaged DNA but dysfunctional and/or deleterious proteins and lipids; (2) levels of such "oxidative stress" have been illustrated to increase throughout the lifespans of humans and drosophila [ and c. elegans? ], and is consistent with the results of rodent dietary restriction; (3) there is a clear correlation between lifespan and oxygen consumption/body weight weight in a number of species; (4) recent work in drosophila has extended lifespan by manipulating the biochemical pathway which metabolizes superoxide and hydrogen peroxide. There is extensive literature on oxidative stress. The genes/proteins involved in free radical metabolism are well-known (see SOD, catalase, glutathione peroxidase in any biochemistry textbook) but their regulation is not well understood. Downstream events (i.e., exactly which important proteins and lipids are modified/damaged) is also not clear. References: Sohal, R.S. & Allen, R.G. (1990) Oxidative Stress as a causal factor in differentiation and aging: a unifying hypothesis. Exp. Gerontology 25:499-522. Stadtman, Earl R. (1992) Protein Oxidation and Aging. Science 257:1220-1224. H. DNA methylation Methylation of cytidine residues of DNA has been correlated with gene expression levels in a number of cases. It is unresolved whether methylation is a cause or result of altered chromatin structure. DNA methylation is thought to be responsible for imprinting, and has been implicated as a mechanism in both development and aging. Overall methylation levels in mice apparently decrease as a function of age from six to twenty-four months, and may subsequently increase. There is an extensive literature on DNA methylation and aging studies are only a small part of this active field. References: Singhal, R.P. (1987) DNA methylation in Aging of Mice. Mechanisms of Ageing and Development, 41:199-210. j. Other III. Aging in model organisms Traditional approaches to genetic and biochemical study include making mutants, and fractionating extracts and assaying for activity. Generating mutant humans and dissecting them is clearly not as ethical, so traditional laboratory organisms are used in many aging studies. This has an advantage that experiments can be performed ethically and efficiently, but a disadvantage that the results may not apply to humans. Aside from obvious morpohological differences, perhaps the strongest argument is that since humans live so long, our genome must have overcome whatever it is that causes other organisms to have such short lifespans. On the other hand, aging even in fruit flies and worms has a striking resemblance to that in humans. A. Humans 1. biomarkers of aging in humans: 2. causes of death: I am having a hard time finding a simple summary of U.S. mortality statistics and would appreciate anyone's contribution here. What I have found is that approximately 40% of all persons will have a neoplasm in their lifetime and that for about 20% of the population this is the cause of death. George Will discussed Sherwin B. Nuland's latest book "How We Die: Reflections on Life's Final Chapter" in the March 7 1994 Newsweek, and claimed that 85% of the aging population "succumbs[s] to one of seven ailments - atherosclerosis, hypertension, adult-onset diabetes, obesity, Alzheimer's and other dementias, cancer, and decreased resistance to infections". The book is apparently quite morbid in its attention to detail, and I suppose I will try to find it although I'm frankly not looking forward to reading the thing. 3. progeroid syndromes: A number of hereditary disorders result in short lifespans during which the senescence process is apparently accelerated. None of them exactly matches the wild-type aging phenotype, but the similarities are quite striking, and one would expect genes causing these syndromes to be significant in regulating the aging process. Traditional genetic linkage analyses are difficult because the diseases are very rare autosomal recessive. A linkage for Werner's syndrome was announced two years ago but I haven't heard of a gene yet. A number of progeroid syndromes have been linked to DNA repair deficiencies, and Werner's has a reported mutator phenotype. [The distinction between DNA repair and general transcription and replication is not entirely clear at this point. It is interesting that not all cellular mutator phenotypes result in premature aging syndromes in the organism.] References: Goto, M. et. al. (1992) Genetic Linkage of Werner's syndrome to five markers on chromosome 8. Nature, 355:735-737 (20 Feb '92) 4. linkages to longevity: A recent publication reports the distribution of alleles implicated in cardiovascular risk at two loci (genes) between French centenarians and a control population aged 20-70. The study was quite large and different distributions were found at both loci. The paper refers to an established linkage between longevity and HLA genotype as well. [Also I believe it is common knowledge that women live generally longer than men, making the Y chromosome a significant longevity determinant.] References: Schachter, F. et. al. (1994) Genetic associations with human longevity at the APOE and ACE loci. Nature Genetics 6:29-32 (january 1994). 5. hormone studies: B. Rodents - mice are the most common mammalian experimental model for genetic research. The mouse is considered to to fairly closely model humans. Murine cells are easily transformed in culture. Mice may have fewer defenses against dysplasia because they are smaller and don't live as long. 1. calorie restriction: It was first observed in the 1930's that rats which were fed less but supplied with proper nutrition lived longer. It has since been determined that the caloric intake is the sole determinant, suggesting that metabolic rate metabolic rate serves as a "genetic clock". However, metabolic rate is not necessarily lowered when the reduced mass of the animal is corrected for. The fact that a large number of physiological and pathological symptoms of aging are delayed in CR animals has made the phenomenon difficult to study. As glucose, insulin, and plasma-free glucocorticoid concentrations are affected, modulation of neuroendocrine regulatory systems has been implicated. The onset of tumors, which kill about 50% of all mice, is delayed in CR mice. No direct evidence exists for any hypothesis regarding the effects of CR. References: Masoro, E.J. (1993) Dietary Restriction and Aging. J. of the Am. Ger. Soc. 41:994-999. Weindruch, R. (1989) Dietary Restriction, Tumors, and Aging in Rodents. J. of Geron. 44(6):67-71. 2. SAM (senescence accelerated mouse): 3. SOD transgenics C. Drosophila 1. Genetic analysis 2. engineered mutants: Flies with extra copies of both Superoxide Dismutase, which converts superoxide anion radical to H2O2, and Catalase, which converts H2O2 to water and oxygen, were shown to have moderately increased lifespan and slightly delayed loss of physical activity. Cellular oxidative stress was clearly reduced as measured by protein carbonyl content. References: Orr, W.C. & Sohal, R.S. (1994) Extension of Life-Span by Overexpression of Superoxide Dismutase and Catalase in Drosophila melanogaster. Science 263:1128-1130 (25 Feb '94) D. C. Elegans 1. backcross analysis 2. age-1 mutant 2. "Methuselah": A recently reported mutant now holds the record for increase in lifespan. A mutation in daf-2, a developmental gene, more than doubles nematode lifespan (18 to 42 days mean). The mutants are "healthy and fertile". References: Kenyon, C. et al. (1993) A C. elegans mutant that lives twice as long as wild type. Nature 366:461-464. See also News & Views (Pertridge & Harvey) from the same issue. E. Other Species 1. yeast 2. sea urchin 3. calorie restriction in primates F. Relationship of biomarkers of aging in humans to those in model organisms IV. Other interesting phenomena, etc. =================================================================== +++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++ =================================================================== From owner-ageing@net.bio.net Sat Jun 04 23:00:00 1994 Path: biosci!agate!howland.reston.ans.net!pipex!lyra.csx.cam.ac.uk!mole.bio.cam.ac.uk!ag24 From: ag24@mole.bio.cam.ac.uk (Aubrey de Grey (Genetics)) Newsgroups: bionet.molbio.ageing Subject: Re: FAQ Date: 5 Jun 1994 16:39:09 GMT Organization: U. of Cambridge, England Lines: 31 Distribution: world Message-ID: <2ssv3d$pj0@lyra.csx.cam.ac.uk> References: <2sspeb$in1@gazette.bcm.tmc.edu> NNTP-Posting-Host: mole.bio.cam.ac.uk In the FAQ, Tim Hughes writes: > [The fact that senescence is a dominant property > suggests that DNA damage is not responsible for > the senescence phenomenon. If senescent cells had > lost a function that immortal cells retained, > then immortality would be dominant. > It seems unlikely that senescence would be due > to a gain of function mutation in all senescent > cells simultaneously. If immortality were due > primarily to a gain of function mutation not present in > senescent cells, again immortality would be > expected to dominate. The remaining possibility > then is that immortality is due to a loss of function, > and that senescent cells have retained the normal > genotype.] I don't see this. Surely all it takes for damage to be dominant is for the damaged DNA to be (before being damaged) a negative regulator of a gene whose expression causes the cell to senesce. This regulation could either be by the gene product of the negative regulator, in which case the dominance of senescence would arise only if dosage were relevant (ie if one dose of regulator could not suppress two doses of senescer), or it could be a direct DNA-DNA cis-regulation, eg where the regulator DNA binds a protein whose attachment inhibits transcription of the gene immediately downstream (namely the senescer), in which case a dosage argument is not necessary. Am I missing something here? Cheers, Aubrey From owner-ageing@net.bio.net Sun Jun 05 23:00:00 1994 Newsgroups: bionet.molbio.ageing Path: biosci!agate!howland.reston.ans.net!gatech!newsxfer.itd.umich.edu!uunet!utcsri!utnut!nott!emr1!news From: woodgold@seismo.emr.ca (Cathy Woodgold) Subject: Re: How evolution works Message-ID: <1994Jun6.144856.22340@emr1.emr.ca> Sender: news@emr1.emr.ca Nntp-Posting-Host: saw19.seismo.emr.ca Reply-To: woodgold@seismo.emr.ca Organization: Geological Survey of Canada References: <2slqaa$dio@nwfocus.wa.com> Date: Mon, 6 Jun 1994 14:48:56 GMT Lines: 46 In article dio@nwfocus.wa.com, venezia@zgi.com (Domenick Venezia) writes: > Cathy Woodgold (woodgold@seismo.emr.ca) wrote: > .. > : helps a lot too.) Anyway, this is one way that bad mutations are weeded out > : in the human species; that method can't be used by an individual who is > : living thousands of years! > Correct me if I misunderstood, but what you are saying is that I should > consent to die for the betterment of human evolution? I'm correcting you. I'm saying nothing of the sort. I don't remember using the word "should" nor any similar word; this is a scientific, not an ethical discussion, isn't it? I'm trying to understand how human evolution works. My reason for doing so is the opposite of what you seem to think I mean. Actually, I think people (most of the time) "should" try to live as long and as healthily as possible. I don't see how this could affect human evolution in a bad way ... especially when one is talking about someone who has already had all the children they're likely to. Having children at an older age may affect their genes a bit, but that's a separate sociocultural issue and is certainly not going to have a major impact on the gene pool. (The better environment, financially, socially and so on, that an older parent tends to be able to provide, is probably much more important than the gene quality. For example, most teenage mothers do not breastfeed their children here in Ottawa.) I think people "should" have children at whatever age they decide is best for their family (or whatever age they choose to) and "should" usually try to live as long as possible and try to help their children be healthy and live as long as possible. I'm intrigued by the possibility that something about telomeres may be useful in helping people live longer, and I'm exploring various sides of the idea, with the hope that I and others may be able to live longer. If I think of something like "Oh, well, it might not work because...." I will say that, too .... not because we shouldn't try to live longer but because that's part of the process of figuring out how to live longer! By the way, I said miscarriages happen; I didn't say we should try to make more of them happen! I gave information about how to cut down the number (excellent nutrition by both parents starting about three months before conception; Dad can go back to junk food after conception) in the hope that some people would use it. I want to help other people to be healthier. Sorry if this sounds like a tirade. :) Cathy TISSATAAFL my personal opinions only From owner-ageing@net.bio.net Mon Jun 06 23:00:00 1994 Path: biosci!daresbury!trane.uninett.no!eunet.no!nuug!EU.net!uunet!nwnexus!flames!venezia From: venezia@zgi.com (Domenick Venezia) Newsgroups: bionet.molbio.ageing Subject: Re: How evolution works Date: 7 Jun 1994 00:41:53 GMT Organization: Northwest Nexus Inc. Lines: 7 Message-ID: <2t0foh$5m8@nwfocus.wa.com> NNTP-Posting-Host: flames.zgi.com X-Newsreader: TIN [version 1.2 PL2] I apparently misconstrued Cathy Woodgold's point in a previous post and I apologize. I also apologize for having misplaced the previous post so I can not go back and re-read it to get it right. And I apologize for having forgotten its main points %-}. Oops. Sorry. Domenick Venezia ZymoGenetics, Seattle, venezia@zgi.com From owner-ageing@net.bio.net Mon Jun 06 23:00:00 1994 Newsgroups: bionet.molbio.ageing Path: biosci!agate!dog.ee.lbl.gov!ihnp4.ucsd.edu!swrinde!pipex!sunic!trane.uninett.no!eunet.no!nuug!EU.net!uunet!nih-csl!newssrv!sabol From: sabol@codon.nih.gov (Steven L. Sabol) Subject: Purification of apoptotic DNA Message-ID: Followup-To: bionet.molbio.ageing Sender: postman@alw.nih.gov (AMDS Postmaster) Organization: National Institutes of Health X-Newsreader: VersaTerm Link v1.1.1 Date: Tue, 7 Jun 1994 16:57:59 GMT Lines: 21 In apoptosis, genomic DNA is usually partially degraded, with a hallmark "nucleosomal ladder" of 190-200 bp and multiples thereof appearing, although in many systems only a minority of the genomic DNA is degraded this far, much of it remaining in 50+-kilobase fragments. To analyze apoptotic DNA, it would seem to be desirable to isolate genomic DNA of all sizes rather than just small ladder DNA. Standard DNA isolation procedures accomplish this, but there are often problems in redissolving ethanol-precipitated high-molecular weight DNA without extensive shearing. Several companies sell genomic DNA purification kits involving ion-exchange columns and protocols that do not include ethanol precipitation. Has anyone had experience with these kits in purifying apoptotic DNA? If so, how does column-kit-purified DNA compare with DNA purified by non-column methods? How do the recoveries of ladder-size DNA vs. 50+-kilobase DNA compare in these column-based kits? Steven L. Sabol Lab. of Biochemical Genetics NHLBI, NIH Bethesda, MD sabol@codon.nih.gov From owner-ageing@net.bio.net Tue Jun 07 23:00:00 1994 Path: biosci!agate!doc.ic.ac.uk!daresbury!trane.uninett.no!sunic!EU.net!uunet!news.delphi.com!usenet From: jarice@delphi.com Newsgroups: bionet.molbio.ageing Subject: Re: desirability of aging. Date: Wed, 8 Jun 94 03:05:31 -0500 Organization: Delphi (info@delphi.com email, 800-695-4005 voice) Lines: 17 Message-ID: References: <9405270056.AA05681@possum.murdoch.edu.au> <15498.9405270859@mailer.leeds.ac.uk> NNTP-Posting-Host: bos1c.delphi.com X-To: Fergus Doherty Fergus Doherty writes: >Would it really be desirable to live for 3-400 years? This would lead to >an increased population, perhaps even more so if it led to more children >spread over a longer period (child bearing period for women would be >greater if ageing slowed?). What effect of such older people would there >be on innovation and social change, might not such a society be dangerously >static? Since the population is increasing at an exponential rate, immortality only changes the population by a constant factor. Thus it doesn't change the nature of the crisis, only the details. If immortality were prevented to keep population under control, then that would be killing one person so another person can have children. The preceeding was taken (and altered slightly) from sci.cryonics FAQ, para3-3. From owner-ageing@net.bio.net Tue Jun 07 23:00:00 1994 Path: biosci!agate!ihnp4.ucsd.edu!swrinde!pipex!doc.ic.ac.uk!susx.ac.uk!bafa1 From: bafa1@central.susx.ac.uk (Sydney Shall) Newsgroups: bionet.molbio.ageing Subject: Re: How evolution works Date: 8 Jun 1994 12:27:30 GMT Organization: University of Sussex Lines: 74 Message-ID: <2t4dfi$e7h@infa.central.susx.ac.uk> References: <2slqaa$dio@nwfocus.wa.com> <1994Jun6.144856.22340@emr1.emr.ca> NNTP-Posting-Host: solx1.central.susx.ac.uk X-Newsreader: TIN [version 1.2 PL2] Cathy Woodgold (woodgold@seismo.emr.ca) wrote: : In article dio@nwfocus.wa.com, venezia@zgi.com (Domenick Venezia) writes: : > Cathy Woodgold (woodgold@seismo.emr.ca) wrote: : > .. : > : helps a lot too.) Anyway, this is one way that bad mutations are weeded out : > : in the human species; that method can't be used by an individual who is : > : living thousands of years! : > Correct me if I misunderstood, but what you are saying is that I should : > consent to die for the betterment of human evolution? : I'm correcting you. I'm saying nothing of the sort. I don't remember using : the word "should" nor any similar word; this is a scientific, not an ethical : discussion, isn't it? I'm trying to understand how human evolution works. : My reason for doing so is the opposite of what you seem to think I mean. : Actually, I think people (most of the time) "should" try to live as long : and as healthily as possible. I don't see how this could affect human evolution : in a bad way ... especially when one is talking about someone who has already : had all the children they're likely to. Having children at an older age : may affect their genes a bit, but that's a separate sociocultural issue and : is certainly not going to have a major impact on the gene pool. (The better : environment, financially, socially and so on, that an older parent tends to : be able to provide, is probably much more important than the gene quality. : For example, most teenage mothers do not breastfeed their children here : in Ottawa.) I think people "should" have children at whatever age they decide : is best for their family (or whatever age they choose to) and "should" usually : try to live as long as possible and try to help their children be healthy and : live as long as possible. I'm intrigued by the possibility that something about : telomeres may be useful in helping people live longer, and I'm exploring various : sides of the idea, with the hope that I and others may be able to live longer. : If I think of something like "Oh, well, it might not work because...." I will : say that, too .... not because we shouldn't try to live longer but because that's : part of the process of figuring out how to live longer! By the way, I said : miscarriages happen; I didn't say we should try to make more of them happen! : I gave information about how to cut down the number (excellent nutrition by : both parents starting about three months before conception; Dad can go back to : junk food after conception) in the hope that some people would use it. I want : to help other people to be healthier. : Sorry if this sounds like a tirade. :) : Cathy TISSATAAFL my personal opinions only I would like to add another thought to the discussion of human evolution and longevity. Presumably if there are genes which modulate longevity, for which there is good experimental evidence, then these genes first appeared and were later modified by mutation and natural selection. It would therefore be useful to find these genes and determine would influence they have on the development of animals. All attempts to lengthen life-span in humans "should" in my view be coupled to improving the health and welfare of all, as well as older people. The "novel" idea that I would advance is that there is no natural selection in human populations since about the beginning of the 20th Century, because in general people are over-riding their biological ability to have many offspring by "social" decisions to limit the number of children. In most parts of the world the number of children achieved is almost entirely a "social" not a "biological" decision. This idea does not exclude the idea that our current biology as humans includes selection over the last million years during which time we have survivied as social Homo sapiens. -- Sydney SHALL, Laboratory of Cell and Molecular Biology, Biology Building, University of Sussex, Brighton, East Sussex BN1 9QG, From owner-ageing@net.bio.net Tue Jun 07 23:00:00 1994 Path: biosci!PCLSP2.KUICR.KYOTO-U.AC.JP!vinz From: vinz@PCLSP2.KUICR.KYOTO-U.AC.JP (Vincenzo Nardi-Dei) Newsgroups: bionet.molbio.ageing Subject: Re: How evolution works Date: 8 Jun 1994 09:18:18 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 18 Sender: daemon@net.bio.net Distribution: world Message-ID: <9406081620.AA06308@pclsp2> NNTP-Posting-Host: net.bio.net Given the fact that in most parts of the world, in the 21st century society, seems that there is no more genetic evolution in the human race and that the human race can not emprouve more due to the lack of a real selective pressure, and it is even possible that it get worse, it seems to me that times are mature to start thinking on becoming immortals. :-) Vincenzo From owner-ageing@net.bio.net Wed Jun 08 23:00:00 1994 Newsgroups: bionet.molbio.ageing Path: biosci!bcm!cs.utexas.edu!swrinde!pipex!sunic!EU.net!uunet!utcsri!utnut!nott!emr1!news From: woodgold@seismo.emr.ca (Cathy Woodgold) Subject: Re: How evolution works Message-ID: <1994Jun9.144615.4576@emr1.emr.ca> Sender: news@emr1.emr.ca Nntp-Posting-Host: saw19.seismo.emr.ca Reply-To: woodgold@seismo.emr.ca Organization: Geological Survey of Canada References: <2t0foh$5m8@nwfocus.wa.com> Date: Thu, 9 Jun 1994 14:46:15 GMT Lines: 79 Thank you for your apology! Apology accepted. I don't have the original post, either. The point I was trying to get across I'll make another attempt at explaining. I'm imagining an inividual who takes drugs to lengthen the telomeres in the cells of his/her body so that he/she can live a long time. My point is that the individual will inevitably get cancer unless some powerfull way of controlling it is found. (Other people on this newsgroup have been making this same point.) I'm making an analogy between two lines of human cells. A "line" of cells is a set of cells such that at any time there is only one which is considered an active member of the line, and the cells are all connected through time with each other via cell reproductive events (mitosis, meiosis and fertilization). Both lines I'm considering are 1000 years long. One is a typical normal cell line existing in a line of humans of normal lifespan. Let's suppose it starts with a sperm cell; then it includes the fertilized egg that that sperm fertilizes; it includes one, at any given time, of the cells of the developing fetus; as the fetus develops ovaries or testicles, the cell line I'm interested in includes one at any time of the cells of those ovaries or testicles (if it were any other part of the fetus' body it wouldn't be a 100-year- long cell line, would it? It would be limited by the individual's lifespan.) Then after that individual grows up, it includes an egg or sperm which is fertilized and becomes another individual, and so on. Now, it's easy to choose such a cell line in retrospect. I can look at my arm under a microscope and say "I'm talking about this one cell, and it's parent cell before the last mitosis, and it's parent, and so on... except that with fertilization there are two parent cells, so I always choose the egg cell in that case. So I'm talking about the parent or egg-parent cells, of this particular cell, going back 1000 years." It's much harder to predict beforehand which cell of a small fetus will be the parent of an egg or sperm which will successfully develop into another human, or which sperm will fertilize an egg and grow, etc. The other line of cells I'm talking about is an imaginary line of cells within the body of an individual who is living 1000 years because that individual takes drugs to lengthen telomeres and takes other steps to live a long time. The point is that the individual is likely to get cancer. This doesn't mean one shouldn't try to live longer; just that one of the major means is battling cancer. The reason the individual is likely to get cancer is as follows. During the normal 1000-year cell line, a lot of natural selection takes place. Seriously defective eggs, sperm and other cells do not form part of the cell line. Fetuses who have seriously damaged genes (caused by poor nutrition, xrays, or other causes) miscarry and don't form part of the 1000-year cell line. Etc. The natural selection favours normal human development. Within the individual who is living 1000 years, a lot of natural selection also takes place. However, most (at least) of this natural selection favours, not normal human development of the body as a whole, but survival, reproduction and success of individual cells and groups of cells. Usually the success of cells contributes to the success of the individual as a whole, and I suppose the natural selection of cells within the body is a necessary part of healthy human development. But it does tend to lead to cancer, which is simply some cells becoming extremely effective. Here's another analogy: J. Lovelock in The Ages of Gaia talks about life on earth as one whole organism. The mechanisms of evolution of Gaia are somewhat different from the mechanisms of evolution of species, since there is just one Gaia (no ongoing natural selection of planets). However, often the evolution by natural selection of species benefits Gaia as a whole in ways which are not exactly coincidental. For example, some organisms exert a beneficial influence on local climate; natural selection for these has us ending up with a lot of species which therefore exert a beneficial influence on the climate as a whole. Evolution and natural selection are very complex things. I keep learning new things about them. For example, it just occurred to me that within our bodies there may be a certain amount of natural selection of cells which prevents cancer; for example, if a precancerous cell tends to suck nutrients away from the cells around it, perhaps it kills them and perhaps this tends to result in its own death, or at least the death of some other precancerous cells, which are likely to be near (because closely related to) the one cell I started talking about. Anyway, the study of the evolution of Gaia may shed some light on the long-term survival of individuals, and vice versa. Cathy TISSATAAFL From owner-ageing@net.bio.net Wed Jun 08 23:00:00 1994 Path: biosci!daresbury!trane.uninett.no!eunet.no!nuug!EU.net!uunet!nwnexus!flames!venezia From: venezia@zgi.com (Domenick Venezia) Newsgroups: bionet.molbio.ageing Subject: Re: How evolution works Date: 9 Jun 1994 20:13:27 GMT Organization: Northwest Nexus Inc. Lines: 35 Message-ID: <2t7t57$3so@nwfocus.wa.com> NNTP-Posting-Host: flames.zgi.com X-Newsreader: TIN [version 1.2 PL2] On 09 June Cathy Woodgold writes: >I'm imagining an inividual who takes drugs to lengthen the telomeres in the >cells of his/her body so that he/she can live a long time. My point is that >the individual will inevitably get cancer unless some powerfull way of >controlling it is found. (Other people on this newsgroup have been making >this same point.) Yes, I agree. Bruce Ames says that cancer goes up with the fifth power of age. Bottom line: if you live long enough cancer will get you. But I am not sure that it follows that if we extend life through telomeric extension, i.e., the suppression of cellular senescence, that the occurrance of cancer would follow the same power function. We need to think about why cancer increases with age. Is it that we are generating more replication errors with age? If so, why are we generating more errors, or are we tolerating more errors? Is it that our immune systems are less efficient at detecting and defeating nascent cancers? I don't know. But one thing I suspect is that the steady progression of cellular senescence is contributing to the steady loss of function we see with ageing. It may be be that the young are resistant to cancer because they basically still have all their cells. Their immune systems are at 100%, their genetic repair functions are at 100%, their tolerance for oxidized protein is still low, etc. Hard dat would help here. If this is the case then extending your telomeres will flatten the cancer power function to some degree. I am in no way advocating that the fight against cancer be lessened, but simply pointing out that preventing cellular senescence may be affecting a whole cascade of age related issues, cancer included. What does TISSATAAFL stand for or mean? Domenick From owner-ageing@net.bio.net Thu Jun 09 23:00:00 1994 Path: biosci!agate!howland.reston.ans.net!spool.mu.edu!nigel.msen.com!zib-berlin.de!news.th-darmstadt.de!news From: dh7y@.pop.th-darmstadt.de (Inst. f. Biochemie) Newsgroups: bionet.molbio.ageing Subject: determination of apoptosis Date: 10 Jun 1994 07:23:30 GMT Organization: TH Darmstadt Lines: 19 Message-ID: <2t94di$11rm@rs18.hrz.th-darmstadt.de> NNTP-Posting-Host: bc3.bc.chemie.th-darmstadt.de X-Newsreader: WinVN 0.90.6 Hello World, in our lab we are starting to investigate apoptosis in general with special regards to endothelial cells. As we read many papers we are confused, because some of the investigators use the phenol/chloroform extraction before loading the DNA on the agarose gel and some investigators donīt extract with phenol. My question is, which method is better or more recommendable? Hoping to get a lot of valuable informations Gangolf Gangolf Schrimpf Institut fuer Biochemie Petersenstrasse 22 D-64287 Darmstadt Tel.: 06151/165157 e-mail: dh7y@pop.th-darmstadt.de From owner-ageing@net.bio.net Thu Jun 09 23:00:00 1994 Path: biosci!agate!howland.reston.ans.net!pipex!uknet!EU.net!uunet!psinntp!sjuvm!yprlbio Nntp-Posting-Host: 149.68.2.20 Date: Thu, 9 Jun 1994 15:58:49 -0400 From: "LOCKSHIN, RICHARD A" Newsgroups: bionet.molbio.ageing Subject: RE: Purification of apoptotic DNA Message-ID: <09JUN94.17256915.0020@sjumusic.stjohns.edu> References: Sender: usenet@sjumusic.stjohns.edu Organization: St. John's University Lines: 32 In article sabol@codon.nih.gov (Steven L. Sabol) writes: >In apoptosis, genomic DNA is usually partially degraded, with a hallmark >"nucleosomal ladder" of 190-200 bp and multiples thereof appearing, although >in many systems only a minority of the genomic DNA is degraded this far, >much of it remaining in 50+-kilobase fragments. > >To analyze apoptotic DNA, it would seem to be desirable to isolate genomic >DNA of all sizes rather than just small ladder DNA. Standard DNA isolation >procedures accomplish this, but there are often problems in redissolving >ethanol-precipitated high-molecular weight DNA without extensive shearing. >Several companies sell genomic DNA purification kits involving ion-exchange >columns and protocols that do not include ethanol precipitation. Has anyone >had experience with these kits in purifying apoptotic DNA? If so, how does >column-kit-purified DNA compare with DNA purified by non-column methods? How >do the recoveries of ladder-size DNA vs. 50+-kilobase DNA compare in these >column-based kits? > >Steven L. Sabol >Lab. of Biochemical Genetics >NHLBI, NIH >Bethesda, MD >sabol@codon.nih.gov >. I agree with you that some people "purify" DNA fragments to the point that there is virtually nothing left other than artifactual fragmenta- tion. Check our article (Zakeri, Lockshin, et al, FASEB J spring of 1993) in which we compared purified DNA and total DNA by end-labeling. Let me know what else you come up with. Richard Lockshin, Dept. Biol. Sci. St. John's University Jamaica NY 11439 718: 990-1854, FAX 718: 380-8543 yprlbio@sjumusic.stjohns.edu From owner-ageing@net.bio.net Thu Jun 09 23:00:00 1994 Path: biosci!agate!dog.ee.lbl.gov!ihnp4.ucsd.edu!sdcc12!jeeves!wsun From: wsun@jeeves.ucsd.edu (Fiberman) Newsgroups: bionet.molbio.ageing Subject: Re: How evolution works Message-ID: <69193@sdcc12.ucsd.edu> Date: 10 Jun 94 19:26:32 GMT References: <9406081620.AA06308@pclsp2> Sender: news@sdcc12.ucsd.edu Organization: University of California, San Diego Lines: 29 Nntp-Posting-Host: jeeves.ucsd.edu In article <9406081620.AA06308@pclsp2> vinz@PCLSP2.KUICR.KYOTO-U.AC.JP (Vincenzo Nardi-Dei) writes: > >Given the fact that in most parts of the world, in the 21st century >society, seems that there is no more genetic evolution in the >human race and that the human race can not emprouve more due to >the lack of a real selective pressure, and it is even possible that >it get worse, it seems to me that times are mature to start thinking >on becoming immortals. > >:-) > >Vincenzo Are you saying that human beings cannot be improved? Has nature produced her finest organisms? This is an interesting assertion. However, we must keep in mind that evolution occurs on a time scale of millions of years. For example, imagine that there is a food shortage in the future and human beings must compete more intensely to survive. In this case, perhaps only the strongest or most intelligent could survive. Isn't this evolution at work? I am not implying that intelligence is soley genetic based, but it is likely to be true to a certain degree. Just as we are evolved from apes, I believe humans of the distant future could be more highly intelligent than present humans. -fm From owner-ageing@net.bio.net Thu Jun 09 23:00:00 1994 Newsgroups: bionet.molbio.ageing Path: biosci!daresbury!trane.uninett.no!sunic!EU.net!howland.reston.ans.net!europa.eng.gtefsd.com!library.ucla.edu!csulb.edu!csus.edu!netcom.com!jabowery From: jabowery@netcom.com (Jim Bowery) Subject: Re: How evolution works Message-ID: Organization: NETCOM On-line Communication Services (408 261-4700 guest) References: <2t7t57$3so@nwfocus.wa.com> Date: Fri, 10 Jun 1994 19:56:09 GMT Lines: 23 venezia@zgi.com (Domenick Venezia) writes: > On 09 June Cathy Woodgold writes: > > >I'm imagining an inividual who takes drugs to lengthen the telomeres in the > >cells of his/her body so that he/she can live a long time. My point is that > >the individual will inevitably get cancer unless some powerfull way of > >controlling it is found. (Other people on this newsgroup have been making > >this same point.) > > Yes, I agree. Bruce Ames says that cancer goes up with the fifth power of > age. Bottom line: if you live long enough cancer will get you. But I am > not sure that it follows that if we extend life through telomeric extension, > i.e., the suppression of cellular senescence, that the occurrance of cancer > would follow the same power function. Understanding how telomerase-based longevity might be induced without cancer requires understanding the point that Domenick brings up as well as the regulatory mechanisms already in place for cells that use telomerase in our bodies at present. If telomerase-based longevity is so cancer-prone, then why isn't everyone wandering around with bone-marrow cancer? -- The promotion of politics exterminates apolitical genes in the population. The promotion of frontiers gives apolitical genes a route to survival. From owner-ageing@net.bio.net Fri Jun 10 23:00:00 1994 Path: biosci!sjubiol.stjohns.edu!rick From: rick@sjubiol.stjohns.edu (Richard Lockshin) Newsgroups: bionet.molbio.ageing Subject: Re: determination of apoptosis Date: 10 Jun 1994 20:46:43 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 16 Sender: daemon@net.bio.net Distribution: world Message-ID: <9406101337.AA15375@sjubiol.stjohns.edu> NNTP-Posting-Host: net.bio.net if you do not have massive, synchronous apoptosis, then the ladder fraction will be vanishingly small. You can improve the possibility of detecting it by using end-labeling, which reduces the bias of mass. Purification of the DNA essentially removes the bulk intact DNA to concentrate the ladder, but you may find that you are measuring only artifactually broken DNA. See our paper (Zakeri, Lockshin et al in the spring of 1993, FASEB J, or articles by F. Oberhammer, M. Sikorska, and J. Isaacs. (If you can't find them by a literature search, check back. I have my database on another computer.) Richard A. Lockshin Dept. of Biol. Sci. St. John's University 8000 Utopia Parkway Jamaica NY 11439 USA Phone: 718: 990 1854 Fax: 718: 380-8543 From owner-ageing@net.bio.net Fri Jun 10 23:00:00 1994 Path: biosci!parcom.ernet.in!music From: music@parcom.ernet.in (Rajeev Upadhye) Newsgroups: bionet.molbio.ageing Subject: (none) Date: 11 Jun 1994 01:01:17 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 16 Sender: daemon@net.bio.net Distribution: world Message-ID: <9406110643.AA02935@parcom> NNTP-Posting-Host: net.bio.net Please cancel my subscription. Rajeev Upadhye ________________________________________________________________________ Fundamentals of Research Methodology | Centre for Development of | Advanced Computing "Take the roots of some tree | Pune University Campus Crush them with some thing | Ganesh Khind, Pune Then give it to someone | Maharashtra, INDIA 411 007 SOMETHING will definitely happen!!!" | Email: music@parcom.ernet.in | Fax : 91 212 337551 ------ PANCHA TANTRA | Phone: 91 212 332461 (A Sanskrit Book of Fairy Tales) | _________________________________________________________________________ From owner-ageing@net.bio.net Sun Jun 12 23:00:00 1994 Newsgroups: bionet.molbio.ageing Path: biosci!agate!howland.reston.ans.net!torn!nott!emr1!news From: woodgold@seismo.emr.ca (Cathy Woodgold) Subject: Re: How evolution works Message-ID: <1994Jun13.144234.26890@emr1.emr.ca> Sender: news@emr1.emr.ca Nntp-Posting-Host: saw19.seismo.emr.ca Reply-To: woodgold@seismo.emr.ca Organization: Geological Survey of Canada References: <2t4dfi$e7h@infa.central.susx.ac.uk> Date: Mon, 13 Jun 1994 14:42:34 GMT Lines: 38 Sydney SHALL wrote: >The "novel" idea that I would advance is that there is no natural >selection in human populations since about the beginning of the 20th >Century, because in general people are over-riding their biological >ability to have many offspring by "social" decisions to limit the number >of children. In most parts of the world the number of children achieved >is almost entirely a "social" not a "biological" decision. I agree that people usually choose how many children they will have. However, I disagree that there is no natural selection! Even if everyone always chose to have exactly two children and those children always survived to have offspring themselves, there would still be natural selection for fast-swimming sperm and healthy egg cells, and for embryos that are capable of developing into babies. However, many people don't have exactly two children. For example, I know someone who had only one child, though she would have liked more, because complications of her diabetes led her to decide not to have any more children. Of course, in a less technological society such a diabetic would have died and had zero children; but having just one child instead of more is still natural selection against the genes, if there are such, that predispose one to diabetes. (More significantly, perhaps, it's natural selection against the cultural practices, passed from parents to children, that predispose one to diabetes. Diabetes depends more on nutrition than on genes.) There is also natural selection for people who love children and want to have lots of children. By the way, humans have evolved, through natural selection, the qualities of responsibility, intelligence, cooperation, etc. and many are now applying these qualities to the survival of the planet by limiting the number of children they have. (Some choose to have zero children because "there are too many people in the world", though they still want some people to have children to continue the species; others might stop, say, at five children, out of a sense of responsibility, though they would have liked to have had eight.) Cathy TISSATAAFL From owner-ageing@net.bio.net Sun Jun 12 23:00:00 1994 Path: biosci!PCLSP2.KUICR.KYOTO-U.AC.JP!vinz From: vinz@PCLSP2.KUICR.KYOTO-U.AC.JP (Vincenzo Nardi-Dei) Newsgroups: bionet.molbio.ageing Subject: Re: determination of apoptosis Date: 12 Jun 1994 22:36:32 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 5 Sender: daemon@net.bio.net Distribution: world Message-ID: <9406130539.AA02910@pclsp2> NNTP-Posting-Host: net.bio.net Use phenol/chloroform extraction. Vinz From owner-ageing@net.bio.net Sun Jun 12 23:00:00 1994 Path: biosci!agate!doc.ic.ac.uk!uknet!EU.net!uunet!dziuxsolim.rutgers.edu!atlantis.rutgers.edu!jin From: jin@atlantis.rutgers.edu (Gavin L. Gim) Newsgroups: bionet.molbio.ageing Subject: It may not be that bad (Re: desirability of aging. Message-ID: Date: 13 Jun 94 05:14:37 GMT References: <15498.9405270859@mailer.leeds.ac.uk> <2s62t5$65c@search01.news.aol.com> <2s7uop$p5n@acmex.gatech.edu> Organization: Rutgers Univ., New Brunswick, N.J. Lines: 29 gt8623b@prism.gatech.edu (William Shelly Hayes) writes: >[....] >The initial aspects of a means to stop aging if it were cheap enough to be >generally available would be devastating to our society. One third of our >society would be back at work (as they would be essentially very knowledgeable >twenty year olds) and the birth rate would not slow down significantly. This >cannot help but to generate a lot of war and other craziness as the >population increases. I think eventually human beings have to leave the earth. It will be highly desirable to live much longer than the natural life span in a spaceship. Travelling between two planets of two different solar systems takes thousands of years if Einstein's prediction that nothing can be faster than light is true. I think the pregresses in physics and engineering will parallel that of biology so when the day comes that ageing can really be stopped, space travelling will not be far away. Therefore, human beings can keep reproducing and living long as long as we expand to other planets. Hopefully, those two technologies, spaceship and life-prolonging, come out at the same time. Then your worries will be solved. Gavin From owner-ageing@net.bio.net Tue Jun 14 23:00:00 1994 Message-ID: <003356Z15061994@anon.penet.fi> Path: biosci!daresbury!trane.uninett.no!eunet.no!nuug!EU.net!news.eunet.fi!anon.penet.fi Newsgroups: bionet.molbio.ageing From: an24923@anon.penet.fi (Vampire Hunter D) X-Anonymously-To: bionet.molbio.ageing Organization: Anonymous contact service Reply-To: an24923@anon.penet.fi Date: Wed, 15 Jun 1994 00:29:02 UTC Subject: don't read this, please Lines: 7 Does this thing work or Not? ------------------------------------------------------------------------- To find out more about the anon service, send mail to help@anon.penet.fi. Due to the double-blind, any mail replies to this message will be anonymized, and an anonymous id will be allocated automatically. You have been warned. Please report any problems, inappropriate use etc. to admin@anon.penet.fi. From owner-ageing@net.bio.net Wed Jun 15 23:00:00 1994 Path: biosci!agate!ihnp4.ucsd.edu!swrinde!pipex!uknet!daresbury!not-for-mail From: Newsgroups: bionet.molbio.ageing Subject: Correct reference Date: 16 Jun 1994 11:25:57 +0100 Lines: 8 Sender: daemon@mserv1.dl.ac.uk Distribution: bionet Message-ID: <2tp9bl$geu@mserv1.dl.ac.uk> Original-To: ageing@dl.ac.uk Few hours ago I posted a small message for carnosine's anti-ageing effects. There was a small mistake in the quoted reference. Before anybody becomes too upset, the correct and complete reference is: McFarland, GA and Holliday, R. (1994) Retardation of the senescence of cultured human diploid fibroblasts by carnosine. Experimental Cell Research, 212: 167-175. Suresh Rattan/Aarhus/Denmark From owner-ageing@net.bio.net Wed Jun 15 23:00:00 1994 Path: biosci!agate!ihnp4.ucsd.edu!swrinde!pipex!doc.ic.ac.uk!susx.ac.uk!bafa1 From: bafa1@central.susx.ac.uk (Sydney Shall) Newsgroups: bionet.molbio.ageing Subject: Re: Anti-ageing discoveries Date: 16 Jun 1994 09:31:39 GMT Organization: University of Sussex Lines: 49 Distribution: bionet Message-ID: <2tp65r$bdp@infa.central.susx.ac.uk> References: <2tp3l7$b8h@mserv1.dl.ac.uk> NNTP-Posting-Host: solx1.central.susx.ac.uk X-Newsreader: TIN [version 1.2 PL2] RATTAN@kemi.aau.dk wrote: : Research on ageing is linked with a search for methods to prevent/delay/ : cure ageing and age-related diseases/symptoms/characterisitcs.The market : for anti-ageing products is unsaturable. Perhaps that is why many of : the senior ageing researchers are now either opening up their own : companies or sitting on consultancy boards of other companies. : Apparently, there is a lot of money to be made!!!!! : Recently, two new discoveries have been published claiming certain : anti-ageing effects on human cells in culture. This week in the journal : EXPERIMENTAL CELL RESEARCH, VOL 212, PP 165, 1994; ROBIN HOLLIDAY : (of Holliday junction fame) has published senescence-retarding effects : of a dipeptide beta-alanyl-L-histidine, called carnosine, on human : fibroblasts. Maintenance of young morphology along with some other : cellular and biochemcial characterisitcs is the main effect seen. There is : a slight increase in cell proliferation too. Even senescence characteristics : can be reversed. Of course, at this stage nothing is known about the : mode of action of such a dipeptide in bringing about so big changes : in cellular physiology, ageing and lifespan. : That was the first report. The other one is coming out or may be it is : already out, I have not seen it yet, in the latest issue of BBRC. : This is about the famous Factor-X as anti-ageing miracle compound. : I cant tell the name yet until I see the published journal. Already : it has taken 8 years of companies-induced blockage on publication. I know : all this because I am the author of this second paper. So, in a day or : two I will tell you the detail of this other compound discovered by : .. : Now get ready with all those mechanistic questions. : Suresh Rattan : Laboratory of Cellular Ageing : Department of Chemistry : Aarhus University : DK-8000 Aarhus - c : Denmark e-mail: Rattan@kemi.aau.dk The message from Suresh Rattan is exciting. If people are interested in the compound carnosine, the dipepetide that he mentions, Alan Hipkiss at King's College, London, England has been studying the "anti-ageing" properties of this compound for some time. It should be said that in this context "anti-ageing" means retarding the loss of physiological function. This may or may not affect death (from other causes), and may or may not be relevant to the biological process of "ageing". -- Sydney SHALL, Laboratory of Cell and Molecular Biology, Biology Building, University of Sussex, Brighton, East Sussex BN1 9QG, From owner-ageing@net.bio.net Wed Jun 15 23:00:00 1994 Path: biosci!daresbury!not-for-mail From: Newsgroups: bionet.molbio.ageing Subject: Anti-ageing discoveries Date: 16 Jun 1994 09:48:39 +0100 Lines: 33 Sender: daemon@mserv1.dl.ac.uk Distribution: bionet Message-ID: <2tp3l7$b8h@mserv1.dl.ac.uk> Original-To: ageing@dl.ac.uk Research on ageing is linked with a search for methods to prevent/delay/ cure ageing and age-related diseases/symptoms/characterisitcs.The market for anti-ageing products is unsaturable. Perhaps that is why many of the senior ageing researchers are now either opening up their own companies or sitting on consultancy boards of other companies. Apparently, there is a lot of money to be made!!!!! Recently, two new discoveries have been published claiming certain anti-ageing effects on human cells in culture. This week in the journal EXPERIMENTAL CELL RESEARCH, VOL 212, PP 165, 1994; ROBIN HOLLIDAY (of Holliday junction fame) has published senescence-retarding effects of a dipeptide beta-alanyl-L-histidine, called carnosine, on human fibroblasts. Maintenance of young morphology along with some other cellular and biochemcial characterisitcs is the main effect seen. There is a slight increase in cell proliferation too. Even senescence characteristics can be reversed. Of course, at this stage nothing is known about the mode of action of such a dipeptide in bringing about so big changes in cellular physiology, ageing and lifespan. That was the first report. The other one is coming out or may be it is already out, I have not seen it yet, in the latest issue of BBRC. This is about the famous Factor-X as anti-ageing miracle compound. I cant tell the name yet until I see the published journal. Already it has taken 8 years of companies-induced blockage on publication. I know all this because I am the author of this second paper. So, in a day or two I will tell you the detail of this other compound discovered by .. Now get ready with all those mechanistic questions. Suresh Rattan Laboratory of Cellular Ageing Department of Chemistry Aarhus University DK-8000 Aarhus - c Denmark e-mail: Rattan@kemi.aau.dk From owner-ageing@net.bio.net Wed Jun 15 23:00:00 1994 Path: biosci!PCLSP2.KUICR.KYOTO-U.AC.JP!vinz From: vinz@PCLSP2.KUICR.KYOTO-U.AC.JP (Vincenzo Nardi-Dei) Newsgroups: bionet.molbio.ageing Subject: re: Anti-ageing discoveries Date: 16 Jun 1994 06:46:48 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 16 Sender: daemon@net.bio.net Distribution: world Message-ID: <9406161349.AA12686@pclsp2> NNTP-Posting-Host: net.bio.net >it has taken 8 years of companies-induced blockage on publication. Suresh, could you please be more explicative? Thank you very much indeed. Vincenzo Nardi-Dei Lab. of Bio-Functional Molecules Institute for Chemical Research Kyoto University Japan From owner-ageing@net.bio.net Thu Jun 16 23:00:00 1994 Path: biosci!agate!ihnp4.ucsd.edu!swrinde!pipex!uknet!daresbury!not-for-mail From: Newsgroups: bionet.molbio.ageing Subject: Humour in ageing Date: 17 Jun 1994 13:58:21 +0100 Lines: 38 Sender: daemon@mserv1.dl.ac.uk Distribution: bionet Message-ID: <2ts6ld$r0@mserv1.dl.ac.uk> Original-To: ageing@dl.ac.uk Something to cheer me up while I am getting free-radicalized due to anxiety; Press RETURN for more... MAIL> #39 17-JUN-1994 14:09:33.37 MAIL I hope no body minds a little humour on this channel. 1. Ageing (for men) is when you remember that you used to run after girls, but you do not remember - "what for?" 2. An elderly couple is sitting near each other at the dinner table. First the woman eats her food slowly and surely while the man gently fans away any flies or other nasty things. After she finishes eating, the man starts to eat his food, and now the woman fans and cleans while he enjoys the food. A social gerontologist watching them is highly impressed and says "I am so pleased to see both of you. You must be having great love and respect for each other." The old woman replies: "To hell with love and respect; we have only one set of dentures...." (So guys, now you know what it means to be elderly in these times of declining national health services......). I love to collect nice, clean jokes (sometimes even not so nice and Press RETURN for more... MAIL> #39 17-JUN-1994 14:09:33.37 MAIL unclean are also OK). So please contribute your stories once in a while to cheer up all of us who are otherwise bored to death looking for single base errors in gerontogenes or not so gerontogenes!! Suresh Rattan/Aarhus/Denmark rattan@kemi.aau.dk From owner-ageing@net.bio.net Thu Jun 16 23:00:00 1994 Path: biosci!daresbury!doc.ic.ac.uk!susx.ac.uk!bafa1 From: bafa1@central.susx.ac.uk (Sydney Shall) Newsgroups: bionet.molbio.ageing Subject: Re: Humour in ageing Date: 17 Jun 1994 16:03:23 GMT Organization: University of Sussex Lines: 52 Distribution: bionet Message-ID: <2tshgb$7ff@infa.central.susx.ac.uk> References: <2ts6ld$r0@mserv1.dl.ac.uk> NNTP-Posting-Host: solx1.central.susx.ac.uk X-Newsreader: TIN [version 1.2 PL2] RATTAN@kemi.aau.dk wrote: : Something to cheer me up while I am getting free-radicalized due to : anxiety; : Press RETURN for more... : MAIL> : #39 17-JUN-1994 14:09:33.37 MAIL : I hope no body minds a little humour on this channel. : 1. Ageing (for men) is when you remember that you used to run after : girls, but you do not remember - "what for?" : 2. An elderly couple is sitting near each other at the dinner table. First : the woman eats her food slowly and surely while the man gently fans away : any flies or other nasty things. After she finishes eating, the man starts : to eat his food, and now the woman fans and cleans while he enjoys the : food. A social gerontologist watching them is highly impressed and says : "I am so pleased to see both of you. You must be having great love and : respect for each other." : The old woman replies: : "To hell with love and respect; we have only one set of dentures...." : (So guys, now you know what it means to be elderly in these times : of declining national health services......). : I love to collect nice, clean jokes (sometimes even not so nice and : Press RETURN for more... : MAIL> : #39 17-JUN-1994 14:09:33.37 MAIL : unclean are also OK). So please contribute your stories once in : a while to cheer up all of us who are otherwise bored to death : looking for single base errors in gerontogenes or not so gerontogenes!! : Suresh Rattan/Aarhus/Denmark rattan@kemi.aau.dk Suresh; Shakespeare had his line on this too!!! "I am not so young as to dote on her for singing, nor so old as to dote on her for anything" -- Sydney SHALL, Laboratory of Cell and Molecular Biology, Biology Building, University of Sussex, Brighton, East Sussex BN1 9QG, ENGLAND. Telephone: +44.273.67.83.03 FAX: +44.273.67.84.33 From owner-ageing@net.bio.net Thu Jun 16 23:00:00 1994 Newsgroups: bionet.molbio.ageing Path: biosci!bcm!cs.utexas.edu!usc!elroy.jpl.nasa.gov!lll-winken.llnl.gov!decwrl!ames!purdue!mozo.cc.purdue.edu!barani From: barani@cc.purdue.edu (barani) Subject: cause-and-effect Sender: news@mozo.cc.purdue.edu (USENET News) Message-ID: Date: Fri, 17 Jun 1994 22:48:43 GMT Organization: Purdue University Computing Center Lines: 47 I wish to comment on a particular type of articles posted in this newsgroup. Many statements like the following appear in these articles: "a cell becomes cancerous because it can lead to ageing..." "certain genes are turned off or turned on because the future generation baby can be healthy..." etc. There is an element of the authors' personal beliefs in these arguments related to cause-and-effect. What happens at the molecular level in a cell cannot be attributed to human desirability and convictions (that Mother Nature intended it that way etc.!). We need to take an IMPERSONAL look at the ageing problem. Please do not make arguments which seemingly imply that there are Supernatural Reasons which is why we age, or, for that matter, "Nature Found a better way to recycle by killing us and producing babies" and so on. We need scientific information about the ageing process. This scientific information is in terms of molecular mechanisms which eventually lead to the morpidity of the macroscopic living system. Why certain genes are turned on or off should be explained on molecular biological reasons rather than that it is good for future etc. In simple words, 'future cannot be made a REASON for the present' while 'present can be EXPLAINED based on the past'. S.Baranidharan Lilly Hall of Life Sciences Purdue University \ / \ / \ / \ / \ / \ / \ / \ / \ / |***|***| |***|***| |***|***| \ **|** / \ **|** / \ **|** / \ *|* / \ *|* / \ *|* / \ | / \ | / \ | / \|/ \|/ \|/ | | | _ | _ _ | _ _ | _ / \ | / \ / \ | / \ / \ | / \ \ \ | / / \ \ | / / \ \ | / / \__\|/__/ \__\|/__/ \__\|/__/ ************************************************************************ |This box is dedicated to the memory of those who spent their lifetimes| | worrying about the age-old problem of the old-age problem. | ************************************************************************ From owner-ageing@net.bio.net Thu Jun 16 23:00:00 1994 Newsgroups: bionet.molbio.ageing Path: biosci!daresbury!trane.uninett.no!sunic!EU.net!howland.reston.ans.net!europa.eng.gtefsd.com!sundog.tiac.net!usenet.elf.com!rpi!utcsri!utnut!nott!emr1!news From: woodgold@seismo.emr.ca (Cathy Woodgold) Subject: Rate of cancer occurrence with age Message-ID: <1994Jun17.163314.4739@emr1.emr.ca> Sender: news@emr1.emr.ca Nntp-Posting-Host: saw19.seismo.emr.ca Reply-To: woodgold@seismo.emr.ca Organization: Geological Survey of Canada References: <2t7t57$3so@nwfocus.wa.com> Date: Fri, 17 Jun 1994 16:33:14 GMT Lines: 121 In article 3so@nwfocus.wa.com, venezia@zgi.com (Domenick Venezia) writes: >... Bruce Ames says that cancer goes up with the fifth power of > age. Bottom line: if you live long enough cancer will get you. But I am > not sure that it follows that if we extend life through telomeric extension, > i.e., the suppression of cellular senescence, that the occurrance of cancer > would follow the same power function. We need to think about why cancer > increases with age. Is it that we are generating more replication errors > with age? ... > What does TISSATAAFL stand for or mean? From this discussion, and from thinking about it, I've gotten a better understanding, I think, of what cancer is and of why we die of old age. Although I still intend to live as long as I can, these thoughts have made me more accepting of my own eventual death. My father once said to me that having children was nature's way of getting a fresh start with healthy organs and now I'm thinking along those lines. Of course, it's still a good idea to try NOT to die. Anyway, this is the way I think cancer works. In order for a cell to become cancerous, it must overcome about five hurdles. These include: beginning to produce the substance that induces blood vessels to grow into a tumour; producing a substance that dissolves the intercellular substance, allowing the cells room to grow; producing telomerase so growth is no longer limited by the length of the telomeres; and other things, I suppose. Each of these hurdles can be overcome by turning on (or off) certain genes that we already have in each of our cells. These genes are needed at certain times for normal development, or are needed by specific kinds of cells in the body, so they're part of the human genome. Accidentally turning on a gene is relatively easy to do ... a lot easier than spontaneously mutating a gene into something new and useful, for example. However, it's not terribly easy; the vast majority of our cells don't become cancerous. There are controls that normally prevent a gene from accidentally turning on. I call a cell precancerous if it's overcome one or more of the hurdles, other than correctly using the genes during normal development. Lemma 1. Everybody has lots of precancerous cells. Evidence: In Cancer and Vitamin C, the authors mention some autopsies that were done on people who died of things other than cancer, and said that it was very common for people to have cancers they didn't know about while they were alive. These cancers didn't seem to bother them. So lots of people have full-fledged or almost full-fledged cancer; there must be a much greater number of people who have cells that have overcome at least one of the hurdles. A bit of math makes this clear. Maybe I'll explain further down. Lemma 2. A fertilized egg that's going to develop into a live baby is neither cancerous nor precancerous. Argument: In order to develop into a live baby, the fetus must develop fairly normally ... have a heart that really beats, etc. In order to develop fairly normally, each of the "hurdles" to cancer is used individually in various ways. For example, blood vessels must be induced to grow a certain amount but not too much. For example, if all the embryo's cells were busy dissolving the intercellular substance, a normal fetus would not take shape. Another argument: the fertilized egg is a totally undifferentiated cell. Perhaps this means all its genes are turned on. As it develops into a fetus, various cells have some genes turned on or off as appropriate, by some mechanism(s). So almost by definition, the fertilized egg can't have genes that are inappropriately turned on. Perhaps as the embryo develops, cells with certain genes turned on simply gravitate towards the part of the body where such genes are appropriate. Lemma 3. Cancer occurs with a rate of about the fifth power of age. Argument: Suppose that "mistakes" that accidentally turn on genes that overcome the "hurdles" to cancer occur at a constant rate. N1 = R1 * NB * t N1 number of cells that have overcome hurdle 1 R1 rate at which hurdle 1 occurs NB number of cells in body t time (i.e. age of individual, from conception) Suppose the "mistakes" occur randomly. That is, a cell that has overcome one hurdle is neither more nor less likely to overcome another hurdle than a normal cell. N12 = (N1 * N2) / NB N12 number of cells that have overcome both hurdle 1 and hurdle 2 N2 number of cells that have overcome hurdle 2 N12345 = (N1 * N2 * N3 * N4 * N5) / NB ** 4 N12345 estimated number of cells that have overcome all 5 hurdles ** exponentiation Substituting, N12345 = (R1*NB*t) * (R2*NB*t) * (R3*NB*t) * (R4*NB*t) * (R5*NB*t)/NB ** 4 = (R1 * R2 * R3 * R4 * R5) * NB * (t ** 5) When N12345 is a lot less than 1, one assumes the person doesn't have cancer. When it's 1 or more, there's probably a cancerous cell, which will then begin dividing and the number of cancerous cells will increase rapidly, no longer constrained by the above equation. This shows that cancer goes up with the fifth power of age; that it goes up linearly with the number of cells in the body; and that it depends, of course, on the rates of various cells overcoming various hurdles. Was Bruce Ames' statment about the fifth power of age based on a similar argument, or was it backed up with experimental evidence? We can reduce our cancer rate by reducing the rates of cells overcoming the various hurdles. We can do this by: avoiding radiation; avoiding pollution or dangerous chemicals; reducing pollution in the environment and in our food; taking antioxidants. Women can reduce their rate of breast cancer by: not taking birth control pills; not having abortions; and breastfeeding their children, if they have any. (There are natural birth control methods now with lower pregnancy rates than the Pill.) In all this, I've totally ignored the role of the immune system in controlling cancer. It's extremely important; lots and lots of cancerous cells are destroyed by the immune system. I don't know why it fails sometimes. Perhaps the main mechanism of vitamin C in controlling cancer is by allowing the immune system to work. Perhaps one of the "hurdles" that cancer overcomes is developing a way to dodge the immune system. Cathy TISSATAAFL From owner-ageing@net.bio.net Thu Jun 16 23:00:00 1994 Path: biosci!daresbury!trane.uninett.no!sunic!EU.net!howland.reston.ans.net!europa.eng.gtefsd.com!sundog.tiac.net!usenet.elf.com!rpi!psinntp!sjuvm!yprlbio Nntp-Posting-Host: 149.68.2.20 Date: Thu, 16 Jun 1994 17:11:08 -0400 From: "LOCKSHIN, RICHARD A" Newsgroups: bionet.molbio.ageing Subject: Re: determination of apoptosis Message-ID: <16JUN94.18558433.0121@sjumusic.stjohns.edu> References: <9406130539.AA02910@pclsp2> Sender: usenet@sjumusic.stjohns.edu Organization: St. John's University Lines: 9 In article <9406130539.AA02910@pclsp2> vinz@PCLSP2.KUICR.KYOTO-U.AC.JP (Vincenzo Nardi-Dei) writes: > >Use phenol/chloroform extraction. > >Vinz I would use both, because extraction may throw away the fragments. Actually, some people (probably improperly) _discard_ the extracted DNA and analyze only the fragments (or artifacts, if you will :-) From owner-ageing@net.bio.net Sun Jun 19 23:00:00 1994 Path: biosci!agate!howland.reston.ans.net!pipex!warwick!not-for-mail From: cuhes@csv.warwick.ac.uk (Malcolm McMahon) Newsgroups: bionet.molbio.ageing Subject: Re: cause-and-effect Date: 20 Jun 1994 10:45:57 +0100 Organization: University of Warwick, Coventry, UK Lines: 16 Message-ID: <2u3ogl$6tb@crocus.csv.warwick.ac.uk> References: NNTP-Posting-Host: crocus-fddi.csv.warwick.ac.uk Mime-Version: 1.0 Content-Type: text/plain; charset=US-ASCII Content-Transfer-Encoding: 7bit In article , barani@cc.purdue.edu (barani) writes: >"a cell becomes cancerous because it can lead to ageing..." >"certain genes are turned off or turned on because the future >generation baby can be healthy..." >etc. > >There is an element of the authors' personal beliefs in these >arguments related to cause-and-effect. This is a familiar cry for scientific "objectivity" of the sort that led to the long dark night of behaviourism in the psycholigal sciences. It missed the point that evolutionary processes, like mental processes are goal directed and can often be best analysed in terms of purpose. Malcolm From owner-ageing@net.bio.net Sun Jun 19 23:00:00 1994 Newsgroups: bionet.molbio.ageing Path: biosci!agate!spool.mu.edu!torn!nott!emr1!news From: woodgold@seismo.emr.ca (Cathy Woodgold) Subject: Re: cause-and-effect Message-ID: <1994Jun20.154241.5723@emr1.emr.ca> Sender: news@emr1.emr.ca Nntp-Posting-Host: saw19.seismo.emr.ca Reply-To: woodgold@seismo.emr.ca Organization: Geological Survey of Canada References: Date: Mon, 20 Jun 1994 15:42:41 GMT Lines: 47 In article 9Ky@mozo.cc.purdue.edu, barani@cc.purdue.edu (barani) writes: > ... > Many statements like the following appear in these articles: > > "a cell becomes cancerous because it can lead to ageing..." > "certain genes are turned off or turned on because the future > generation baby can be healthy..." > etc. > ... > Please do not make arguments which seemingly imply that > there are Supernatural Reasons which is why we age, or, for that matter, > "Nature Found a better way to recycle by killing us and producing babies" > and so on. I don't know about the first quoted statement, but the second seems to be an attempt to approximate what I wrote, so I'm responding. I did not make any statement meaning quite the same as either of the quoted statements, and I don't think anybody else did, either. If you're going to criticize what people say, please try to quote them exactly; criticize what they said, not what they didn't say! If you think I was implying that there are Supernatural Reasons or that being killed by Nature is "better", you have misunderstood me. Perhaps I didn't express my ideas clearly enough. (Why do people keep misunderstanding me? I think this is the second time I've been misunderstood while trying to explain the same concept. Am I not explaining it very well, or is it a very difficult concept to grasp?) Basically, the concept I was working with was that there are a lot of fertilized human eggs. A lot of these grow into babies, and a lot of them don't. A lot of the ones that don't grow into babies don't grow into babies because they have seriously defective genes. It is "natural selection" that decides which genes are so seriously defective that a baby can't result. If you don't understand the concept of "natural selection": ask me or somebody else to explain it. Anyway, "natural selection" is NOT a "Supernatural Reason". It's a scientific concept. And once again, I DON'T THINK IT'S A GOOD THING FOR PEOPLE TO DIE!! and please stop saying that I'm saying that when I'm not!! By the way, somebody asked what TISSATAAFL meant, and I forgot to answer. It's my answer to TANSTAAFL, which stands for "There Ain't No Such Thing As A Free Lunch" (from The Moon Is a Harsh Mistress, by R. Heinlein). Ask again if you still can't figure it out. Cathy TISSATAAFL From owner-ageing@net.bio.net Sun Jun 19 23:00:00 1994 Path: biosci!agate!howland.reston.ans.net!pipex!lyra.csx.cam.ac.uk!warwick!not-for-mail From: cuhes@csv.warwick.ac.uk (Malcolm McMahon) Newsgroups: bionet.molbio.ageing Subject: Re: cause-and-effect Date: 20 Jun 1994 16:05:44 +0100 Organization: University of Warwick, Coventry, UK Lines: 22 Message-ID: <2u4b88$5su@crocus.csv.warwick.ac.uk> References: <2u3ogl$6tb@crocus.csv.warwick.ac.uk> <2u41a9$2nq@infa.central.susx.ac.uk> NNTP-Posting-Host: crocus-fddi.csv.warwick.ac.uk Mime-Version: 1.0 Content-Type: text/plain; charset=US-ASCII Content-Transfer-Encoding: 7bit In article <2u41a9$2nq@infa.central.susx.ac.uk>, >Unlike mental processes, evolutionary processes are NOT goal-directed. >The current view of evolution very clearly observes that mutations >happen in cells (or organisms) and then afterwards natural selection >works against all those forms that are not able to produce the most >offspring over an extended time period. > >The evolution of mental properties are odd and unique precisely because >the ability of a brain to develop "purpose" and "objevtives". Natural >selection has neither of these properties. > I think you could "model" evolutions behaviour pretty well on the assumption that it "aims" to fill all available eccological niches. My reading on genetic algorithms shows me that evolution can be regarded as an exteremly powerful general purpose problem solving technique. It may well be that mental processes actually solve problems in the same way: by selecting, combining and mutating ideas. To me evolution _is_ a thought process. Malcolm From owner-ageing@net.bio.net Sun Jun 19 23:00:00 1994 Path: biosci!agate!howland.reston.ans.net!pipex!uknet!doc.ic.ac.uk!susx.ac.uk!bafa1 From: bafa1@central.susx.ac.uk (Sydney Shall) Newsgroups: bionet.molbio.ageing Subject: Re: cause-and-effect Date: 20 Jun 1994 12:16:09 GMT Organization: University of Sussex Lines: 32 Message-ID: <2u41a9$2nq@infa.central.susx.ac.uk> References: <2u3ogl$6tb@crocus.csv.warwick.ac.uk> NNTP-Posting-Host: solx1.central.susx.ac.uk X-Newsreader: TIN [version 1.2 PL2] Malcolm McMahon (cuhes@csv.warwick.ac.uk) wrote: : In article , : barani@cc.purdue.edu (barani) writes: : >"a cell becomes cancerous because it can lead to ageing..." : >"certain genes are turned off or turned on because the future : >generation baby can be healthy..." : >etc. : > : >There is an element of the authors' personal beliefs in these : >arguments related to cause-and-effect. : This is a familiar cry for scientific "objectivity" of the sort that : led to the long dark night of behaviourism in the psycholigal sciences. : It missed the point that evolutionary processes, like mental processes : are goal directed and can often be best analysed in terms of purpose. : Malcolm Unlike mental processes, evolutionary processes are NOT goal-directed. The current view of evolution very clearly observes that mutations happen in cells (or organisms) and then afterwards natural selection works against all those forms that are not able to produce the most offspring over an extended time period. The evolution of mental properties are odd and unique precisely because the ability of a brain to develop "purpose" and "objevtives". Natural selection has neither of these properties. -- Sydney SHALL, Laboratory of Cell and Molecular Biology, Biology Building, University of Sussex, Brighton, East Sussex BN1 9QG, ENGLAND. Telephone: +44.273.67.83.03 FAX: +44.273.67.84.33 From owner-ageing@net.bio.net Sun Jun 19 23:00:00 1994 Newsgroups: bionet.molbio.ageing Path: biosci!agate!howland.reston.ans.net!spool.mu.edu!torn!nott!emr1!news From: woodgold@seismo.emr.ca (Cathy Woodgold) Subject: Re: cause-and-effect Message-ID: <1994Jun20.154750.6212@emr1.emr.ca> Sender: news@emr1.emr.ca Nntp-Posting-Host: saw19.seismo.emr.ca Reply-To: woodgold@seismo.emr.ca Organization: Geological Survey of Canada References: <2u3ogl$6tb@crocus.csv.warwick.ac.uk> Date: Mon, 20 Jun 1994 15:47:50 GMT Lines: 27 In article 6tb@crocus.csv.warwick.ac.uk, cuhes@csv.warwick.ac.uk (Malcolm McMahon) writes: > In article , > barani@cc.purdue.edu (barani) writes: > >"a cell becomes cancerous because it can lead to ageing..." > >"certain genes are turned off or turned on because the future > >generation baby can be healthy..." > >etc. > > > >There is an element of the authors' personal beliefs in these > >arguments related to cause-and-effect. > > This is a familiar cry for scientific "objectivity" of the sort that > led to the long dark night of behaviourism in the psycholigal sciences. > It missed the point that evolutionary processes, like mental processes > are goal directed and can often be best analysed in terms of purpose. > > Malcolm I agree! Science is a lot more than objectively proven facts. Science also comprises creative thinking, hypotheses, theories, ideas, "personal beliefs" which affect creative thinking and help lead to hypotheses, and so on. And evolution is quite complex, and I find it gets tiresome to keep repeating, "the ones that were less fit were less likely to survive, so the ones that survived were more likely to have trait X" ... it's so much easier to say "we have eyes so that we can see", etc. From owner-ageing@net.bio.net Sun Jun 19 23:00:00 1994 Path: biosci!daresbury!trane.uninett.no!eunet.no!nuug!EU.net!howland.reston.ans.net!europa.eng.gtefsd.com!library.ucla.edu!ihnp4.ucsd.edu!news.acns.nwu.edu!uicvm.uic.edu!u56149 Organization: University of Illinois at Chicago, ADN Computer Center Date: Mon, 20 Jun 1994 11:33:38 CDT From: Message-ID: <94171.113338U56149@uicvm.uic.edu> Newsgroups: bionet.molbio.ageing Subject: Humor in Ageing Lines: 11 Old Deans never die; they just loose their faculties. =============================================================================== + Gerald L. Bartlett, M.D., Ph.D. Phone: 309-671-8440 + + Professor and Chairman of Pathology FAX: 309-671-8439 + + University of Illinois College of Medicine @ Peoria + + Box 1649, Peoria, IL 61656-1649 e-mail: jlb@uic.edu + + 1 Illini Drive, Peoria, IL 61605-2576 u56149@uicvm.cc.uic.edu + =============================================================================== From owner-ageing@net.bio.net Sun Jun 19 23:00:00 1994 Newsgroups: bionet.molbio.ageing Path: biosci!daresbury!trane.uninett.no!sunic!EU.net!howland.reston.ans.net!europa.eng.gtefsd.com!news.umbc.edu!haven.umd.edu!purdue!mozo.cc.purdue.edu!barani From: barani@cc.purdue.edu (barani) Subject: scope of bionet.molbio.ageing Sender: news@mozo.cc.purdue.edu (USENET News) Message-ID: Date: Mon, 20 Jun 1994 18:24:38 GMT Organization: Purdue University Computing Center Lines: 81 >Article: 796 of bionet.molbio.ageing >From: woodgold@seismo.emr.ca (Cathy Woodgold) >I don't know about the first quoted statement, but the second seems to >be an attempt to approximate what I wrote, so I'm responding. I did not >make any statement meaning quite the same as either of the quoted statements, >and I don't think anybody else did, either. If you're going to criticize >what people say, please try to quote them exactly; criticize what they >said, not what they didn't say! If I criticize what people didnt say, then these people have nothing to feel offended about either!! I have deliberately avoided refering to articles in order to emphasize the scope of this newsgroup rather than picking on people. Again, this newsgroup is "bionet.molbio.ageing" and when I see an article that is far from the topic, I am compelled to send signals. We are interested in finding the molecular biological reasons for ageing and I am sure I will find support from those vast majority of silent readers of this newsgroup. We are not interested in articles which propose justifications for our ageing or even trying to define 'scientific objectivity'. I hope this message is taken in the right spirit and that it does not open a thread of articles. > If you think I was implying that there are Supernatural Reasons or that >being killed by Nature is "better", you have misunderstood me. Perhaps I >didn't express my ideas clearly enough. (Why do people keep misunderstanding >me? I think this is the second time I've been misunderstood while trying to >explain the same concept. Am I not explaining it very well, or is it a >very difficult concept to grasp?) > Basically, the concept I was working with was that there are a lot >of fertilized human eggs. A lot of these grow into babies, and a lot >of them don't. A lot of the ones that don't grow into babies don't grow into babies because they have seriously defective genes. It is "natural >selection" that decides which genes are so seriously defective that a >baby can't result. If you don't understand the concept of "natural selection": ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ >ask me or somebody else to explain it. Anyway, "natural selection" is NOT ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ You cannot intimidate someone and also expect them to discuss science. I dont see any reason for you to feel hurt personally when I had made a very general comment requesting every