Login

Join for Free!
112340 members


Human aging

Genetics as it applies to evolution, molecular biology, and medical aspects.

Moderator: BioTeam

Postby pomkon » Sun Jan 11, 2009 11:29 pm

A cruical question: stem cells do not go under replicative senescence because it has telomerase. As all cells have its DNA damage and mutations, then stem cells would accumulate more abnormalities than somatic ones, so they die off quicker, and should be lost quicker?
pomkon
Garter
Garter
 
Posts: 7
Joined: Tue Jan 06, 2009 11:10 pm

Postby biohazard » Mon Jan 12, 2009 7:55 am

Well, I guess there is at least one good example of "anti-aging" mutations: birds seem to have evolved to be more tolerant to oxidative stress from their metabolism, and thus most birds live considerably longer than most mammals of similar size. This is due to mutations in the genes that negate free radicals or other such metabolical by-products.

It seems that both mammals and birds have the "tools" required for fixing most of the mutations or damage caused by chance or environmental factors. So could these mechanisms be more efficient, for example, to give us an extra 100 years of life time? I don't know, but at least the bird example above indicates that evolution-wise it could easily happen. But why is it not so? Maybe, because like already mentioned in some previous post, evolution has "found it necessary", so to speak, to ensure that we die in due time: our telomeres diminish until we cannot repair ourselves any more, so we'd die anyway even if we could fix every single mutation or all damage in our genomes. So maybe there just hasn't been evolutionary pressure to give us any better means to fight mutations or oxidative damage etc., because we'd be dead anyway? Or if not dead just yet, too old to have any more offspring, and that is what counts - no need to keep us alive after that...
User avatar
biohazard
King Cobra
King Cobra
 
Posts: 776
Joined: Sun Apr 08, 2007 6:45 pm

Re: Human aging

Postby jonmoulton » Tue Jan 13, 2009 8:31 pm

Hi pomkon,

I ran across a book that addresses your topic. Though it's a bit spendy, this addresses aging and genes. If nothing else it's worth scanning the topics in the table of contents.

http://www.cshlpress.com/default.tpl?ac ... datarq=638

Molecular Biology of Aging
(Cold Spring Harbor Monograph Series 51)
Edited By Leonard P. Guarente, Massachusetts Institute of Technology, Cambridge; Linda Partridge, University College London, UK; Douglas C. Wallace, University of California, Irvine
© 2008 • 610 pp., illus., index
Hardcover • $135 • ISBN 978-087969824-9


Contents

1. The Human Mitochondrion and Pathophysiology of Aging and Age-related Diseases
D.C. Wallace
2. Sirtuins: A Universal Link between NAD, Metabolism, and Aging
S.-i. Imai and L. P. Guarente
3. Calorie Restriction in Lower Organisms
S.L. Helfand, J.H. Bauer, and J.G. Wood
4. Evolutionary Theory in Aging Research
S.N. Austad and T.B.L. Kirkwood
5. An Overview of the Biology of Aging: A Human Perspective
G.M. Martin and C.E. Finch
6. p53, Cancer, and Longevity
L.A. Donehower and A.J. Levine
7. Aging Processes in Caenorhabditis elegans
H.A. Tissenbaum and T.E. Johnson
8. Cellular Senescence: A Link between Tumor Suppression and Organismal Aging?
J.M. Sedivy, U.M. Munoz-Najar, J.C. Jeyapalan, and J. Campisi
9. Genome-wide Views of Aging Gene Networks
S.K. Kim
10. Aging in Mammalian Stem Cells and Other Self-renewing Compartments
D.J. Rossi and N.E. Sharpless
11. Yeast, A Feast: The Fruit Fly Drosophila as a Model Organism for Research into Aging
L. Partridge and J. Tower
12. DNA Repair and Aging
V.A. Bohr, D.M. Wilson, III, N.C. de Souza-Pinto, I. van der Pluijm, and J.H. Hoeijmakers
13. Extended Life Span in Mice with Reduction in the GH/IGF-1 Axis
J.J. Kopchick, A. Bartke, and D.E. Berryman
14. Alzheimer’s Disease: Genetics, Pathogenesis, Models, and Experimental Therapeutics
P.C. Wong, D.L. Price, L. Bertram, and R.E. Tanzi
15. How Does Calorie Restriction Increase the Longevity of Mammals?
R. Weindruch, R.J. Colman, V. Pérez, and A.G. Richardson
16. Determination of Aging Rate by Coordinated Resistance to Multiple Forms of Stress
G.J. Lithgow and R.A. Miller
17. Molecular Mechanisms of Aging: Insights from Budding Yeast
S.-J. Lin and D. Sinclair
18. Genetics of Exceptional Longevity
T.T. Perls and P. Sebastiani
19. Mammalian Metabolism in Aging
P. Puigserver and C.R. Kahn
20. Telomeres and Telomerase in Aging and Cancer
J.W. Shay and W.E. Wright
User avatar
jonmoulton
Viper
Viper
 
Posts: 421
Joined: Fri Feb 15, 2008 5:38 pm
Location: Philomath, Oregon, USA


Postby biohazard » Wed Jan 14, 2009 12:04 pm

Pomkon, about that crucial question of yours:

I'm not sure about this, but I'd guess that stem cells have good enough mechanisms of DNA repair to allow them survive as long as the human body in general. Surely an isolated stem cell can kick the bucket just like any cell, but there is a large enough reservoir of stem cells to accommodate our needs. Mutations eventually do accumulate in stem cells; that is one reson why many cancers originate from poorly differentiated cells (= close to their stem cell stage).

Whether stem cells gain mutations faster than differentiated cells I do not know. I'd guess the rate of mutation is dependent on the given cell's exposure to environmental agents, metabolic stress, mutagens or such other outside factors. Furthermore, what genes are active in the cell determines the effects of the mutations: a (specialised?) cell with only some of its genes active and without mitotic activity hardly notices most of the mutations in its genome, because they take place is shut down genes. So I'd guess even a fairly large number of mutations in, say, a muscle cell or a neuron would have relatively little effect. But of course, in embryonic cells they could be disastrous.

I think if we want to go deeper into this topic we really need to read that book mentioned in the previous post :P At least I'm now close to the limits of my understanding what comes to the mechanisms of aging... although this is a very interesting topic, so just ask if you have any more questions - let's see if there's still something I know about this ;)
User avatar
biohazard
King Cobra
King Cobra
 
Posts: 776
Joined: Sun Apr 08, 2007 6:45 pm

Postby biohazard » Sun Jan 25, 2009 6:47 pm

I just noticed I made an error when claiming that Dawkins says we die of old age so as to leave more room for our offspring. Actually in "The Selfish Gene", he writes that this kind of thinking would be "acting for the good of species", which is not what the genes do - they only act for the good of themselves, and if the genes in you or me could make one of us to live a thousand years and produce offspring all the time, then the genes just might do that.

What Dawkins tells in his book instead is Peter Medawar's theory of dying of old age: there are numerous genes in us that are beneficial in us before or when we get to reproductive age, but after that they may actually turn out to be disadvantageous. It is just that genes that might kill us young do not get passed to our children (and thus rarely exist, that is why children suffer much less from cancer, for example), but the ones that might kill us when we're old easily get passed on to the children as well, and thus are also much more common. These genes are e.g. the ones that are often linked to cancer. So what Dawkins (and Medawar originally) says is that many "old age" genes such as oncogenes are just evolutionary byproducts, something that come along because they only kill us after we've already had children. Of course, these genes may have some useful purpose during the early years of human life, so some of them can actually help us - before they kill us :)

Based on this theory, Medawar also has an interesting idea about how you could easily extend the human life (theoretically) on the long run: if people would only have children after they are, say, 40 years of old, then these people would have lots of genes that allow them to live long enough to reproduce in old age, and also no genes (obviously) that kill them before 40. Then for their children, the limit would be raised for few years for every generation, so again the people with good longevity genes, and especially no cancer genes activating before that age would be selected. This way you could slowly select the individuals that carry few and eventually no pro-cancer cancer or other old-age genes, because the genes "could not afford" to kill people too early. Well, this was a pretty poor summary of the idea, but maybe you got it. If not, then check out The Selfish Gene or some of Medawar's works.
User avatar
biohazard
King Cobra
King Cobra
 
Posts: 776
Joined: Sun Apr 08, 2007 6:45 pm

Postby biohazard » Sun Jan 25, 2009 7:45 pm

Oh, and this brought something else into my mind: they've done similar tests with Drosophilia and I think also with mice - you take the offspring of the long-lived animals and let them breed. Then from their offspring, pick the ones whose parents lived the longest and repeat. I think they've managed to vastly increase the life span of these animals with this procedure.

Apparently, in the nature, living extra long just isn't anything so useful that there'd be evolutionary pressure towards it more than to ensure that there will be offspring, which is why the maximum age of a given organism is what it is even if it didn't die because of hunger, disease or predation (which probably take more than 99% of critters in the wild...)
User avatar
biohazard
King Cobra
King Cobra
 
Posts: 776
Joined: Sun Apr 08, 2007 6:45 pm

Re: Human aging

Postby Omnesion » Sat Jan 23, 2010 4:42 am

I very much enjoyed reading this exchange of ideas regarding aging, and I'm very interested in the topic of longevity/immortality, as you guys/gals seem to be. I'm new to this forum, so I don't really have much to add at the moment. I did want to ask a question about an idea I've had. I don't know if this is, or has ever been tried actually...but I was wondering if anyone or any group of individuals has ever tried to come up with a methodology for artificially selecting for longer lived individuals, thereby creating longer lived large animals (especially primates, et al). I know I remember reading about this being done in smaller organisms, but I was curious about how this might be done in larger mammels. Granted, it wouldn't be terribly beneficial to the ones doing the research or experiments, but it might lead to a way to better understand and eventually "cure" the "disease" of aging. I'm asking on here about this particular avenue, because it's not really my area of study (mine being the prolonging of an existing human life and possible ways to reverse the processes of aging), and since the human genome has now been mapped, and given the current/ever expanding processing power of computers, I was wondering if this is being done either in the lab (I don't see this as a real possibility due to the extremely long time frame involved), or in in the virtual lab (computer modeling)? Thanks and best wishes to all. :)
Omnesion
Garter
Garter
 
Posts: 3
Joined: Sat Jan 23, 2010 4:24 am

Postby Omnesion » Sat Jan 23, 2010 4:44 am

Wow...okay, I didn't see your post about the experiments regarding the drospophilia/mice before I made my previous post Biohazard! :)
Omnesion
Garter
Garter
 
Posts: 3
Joined: Sat Jan 23, 2010 4:24 am

Re: Human aging

Postby zami'87. » Sat Jan 23, 2010 3:09 pm

Unfortunately I don't have time to read all posts right now but I read about regenerative capabilities of cells transplated from old to young mouse..It's more about factors from surrounding(ligands) as when such cells are transplated to young mouse they increase proliferation.Also some study in mice showed that clone mice have problems but it seems their offspring don't..it's all settled in next generation..I can't find the exact page..but the book is Essentials of stem cell biology by Robert Lanza et al.
Also oncogenes like Myc bind to promoter of key subunit of telomerase and increase number of divisions etc...
Every man is a star whose light can make shadows dance differently and change our view of landscape permanently***
User avatar
zami'87.
Coral
Coral
 
Posts: 257
Joined: Sat Mar 05, 2005 6:56 pm
Location: Serbia

Previous

Return to Genetics

Who is online

Users browsing this forum: No registered users and 1 guest

cron