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Tumor-suppressing Gene Contributes to Aging 145

Posted by CowboyNeal
from the growing-old dept.
Van Cutter Romney writes "Scientists have discovered a tumor suppressing gene which also leads to aging in stem cells. The gene also known as p16INK4a when removed from 'knockout' mice resulted in older mice having organs as healthy as younger ones. However they didn't live any longer than normal mice. The new study was confirmed by three independent researchers from Harvard, UNC Chapel Hill and University of Michigan."
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Tumor-suppressing Gene Contributes to Aging

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  • Old news... (Score:3, Interesting)

    by elysian1 (533581) on Thursday September 07, 2006 @09:55PM (#16063662)
    Isn't this talking about the same thing as this article: http://science.slashdot.org/science/05/04/06/23302 49.shtml?tid=191&tid=14 [slashdot.org] which was posted here over a year ago? I guess this is pretty good for slashdot to go over a year without reposting a similar story.
  • by Meccanica (980734) on Thursday September 07, 2006 @10:00PM (#16063672)
    although it does not follow directly from this discovery, is the question: If you could change the balance at any point, what would it mean to be able to choose between heightened risk of cancer and some of the worse effects of old age? What a choice to have to make. (AFAIK, this is not even an issue, just something I thought of after hearing of it. I did not RTFA, but I heard this same discovery reported on the news recently.)
  • Hmm. (Score:3, Interesting)

    by Lord Aurora (969557) on Thursday September 07, 2006 @10:13PM (#16063728)
    If the organs in the older mice were just as healthy as those in younger mice, how did they not live longer? It would seem to me that if your organs are perfectly healthy, you'll live. Wonder what the catch is.
  • by RsG (809189) on Thursday September 07, 2006 @10:34PM (#16063815)
    Actually, genetic safeguards are potentially more important than immune response in many ways.

    The immune system is handicapped by the fact that with at least some types of cancer, there is comparatively little difference between the malignant and healthy cells. If it can't tell them apart, it can't stop the cancer from developing or spreading. You're right in that the immune system can sometimes stop cancer, but from a survival standpoint it's better not to get it in the first place.

    So we have genes in place to limit cell replication. It's been suggested that aging is an inevitable side effect of these limits (take a look at telomeres for instance). Just the immune system by itself, or just the genetic protections by themselves, isn't enough; you really want both defenses.

    Oversimplified, the genetic element is why some cancers run in family lines, and the immune element accounts for why some cancers develop when the immune system is weakened (like KS in AIDS patients).
  • by deltacephei (842219) on Thursday September 07, 2006 @11:52PM (#16064042)
    I agree that it is unnecessary to call out one political group and to globally label members of that group inept and incompetent. It is a separate question entirely to judge the education of all members of government and the extent to which this informs their decision making.

    But, it has been partisan politics that has interfered greatly with science for quite some time now. In particular, politicians have been bent to the will of religious groups. Yet these same groups daily depend on the fruits of science, engineering and technology for their existance. It's a cafeteria approach - they want to be able to lord over science as they see fit and coerce politicians to force a policy consistent with *their* views. This is not the way of science. Science is secular and depends crucially on adherence to the scientific method.

    The relevant point made in that post is that other countries will in fact not hold themselves back with stem cell research. The breakthroughs will happen outside US soil. US citizens with means will continue to travel outside their border to seek treatment not available in their own country. One also wonders if US trained scientists will become fed up with tightening scrutiny of their work and simply themselves immigrate elsewhere to continue research as well. Although this seems preposterous given the high caliber of the US university system and laboratory facilities, I don't see it out of the realm of possibility.
  • by Ungrounded Lightning (62228) on Friday September 08, 2006 @12:16AM (#16064123) Journal
    In this present work, it is a gene that, in a way, computes a differential equation--weighing the importance of replacing cells using stem cells from its cache against the risk that the replication of cells will result in a cancerous cell. "To offset the increasing risk of cancer as a person ages, the gene gradually reduces the ability of stem cells to proliferate."

    If I understand it correctly, this is a SLIGHT mischaracterization. It's not about risk of creation of cancer cells so much as it is about limiting tumor size - generally in malfunctioning differentiated cells - and limiting stem cells is an undesirable side-effect of how it's done (though it WOULD also limit a stem-cell tumor, if such exist).

    The mechanism (or set of mechanisms) is a limit on how many times a non-gamette cell may replicate. Thus when a cell mutates so that it, and its progeny, continue to replicate (ignoring their normal limits), the resulting tumor reaches a maximum size (say-pea sized) and stops growing. (It may even die off, as cells die TRYING to replicate with an "expired meter", or are no longer replaced fast enough to stay ahead of immune-system attacks).

    The smaller the tumor when it hits the limit, the better (and the less likely some cell within it will acquire the ADDITIONAL mutations necessary to escape this limit, founding an "immortalized" tumor cell line). But there's the downside that the limit also results in cellular senescence - inability of the body to replace tissue in late age, because the "counter" in the otherwise-fine cells is running out.

    So the limit apparently evolves with the typical lifespan of the population, allowing enough replication that cellular senescence doesn't begin to occur in normal inividuals until virtually all of them would be dead (or otherwise no longer an asset to the species) due to other causes. (I vuagely recall reports of research suggesting the typicall setting is something like twice as many cell replications as are necessary to avoid senescence by the age where about 95% of the population would be dead.)

    Meanwhile other protective mechanisms (such as the metabolically-expensive production of antioxidant enzymes) co-evolve to trade off keeping the cancer rate down against resource consumption, given the typical lifespan due to risks and the cell-reproductive limit setting. (THESE are the "twiddle settings" that trade off CREATION of a cancer cell against other life-shortening factors.)

    The settigs of these protective mechanisms apparently evolve quite rapidly, so they tend to closely track the lifespan-due-to-circumstances of most species that have been in their niche for a while. But the human lifespan has been drastically extended in a period that is evolutionarilly VERY short, thanks to weapons (protection against predation and improved hunting success), agriculture, animal domesitication, lore transmission, medicine, and other technological and cultural improvements in lifestyle. So plenty of people live to the "threescore and ten" or so years when the current setting of the cell replication limit tends to cause fatal system failures.

    Research such as this, identifying the details of the mechanisms, should lead to interventions to compensate for the now incorrectly-low setting of this "tuning knob" in the human genome.
  • by Anonymous Coward on Friday September 08, 2006 @12:24AM (#16064142)
    The assumption that you made incorrectly was that the probability for a mutation is constant. It is infact cumulative. While the chance that any one healthy cell will mutate is constant, a mutated cell will always produce another mutated cell. Thus the total number of expected mutations goes up everytime a cell divides.

    Look at this statistically.

    Everytime a cell divides there is probablitly P that the cell mutates.
    Everytime a cell ages 1 day there is a probability Q that the cell is damaged.
    Since we must maintain a constant number of cells we assume that everytime a cell divides the "Old" cell dies.

    If we make the simplified assumption that all cells must divide at the same time then we must choose to either (1)let the cells divide or (2)let the cells age one more day.

    There is an obvious strategy to keeping the greatest ratio of healthy cells in the body. We will choose whichever action results in the least expected number of unhealthy cells.

    If P Q (which it should be) the strategy would be to divide every chance you get until the probability of getting a mutation is greater then the probability of having cell damage. You will then alow the cell to age and the ballence will swing back in the other direction.

    As you continue this pattern you will find that it is optimum to have cells divide less and less frequently. Eventually the probability of mutation will be so high that the best strategy is to simply stop cell division all together although it is unlikey that anything will live long enough to reach thsi point.

    This is an oversimplification but the point is still valid. The best strategy for survival changes constantly.

  • by Slashdiddly (917720) on Friday September 08, 2006 @12:38AM (#16064191)
    So, if I understand it correctly, if we were able to prevent cancer (by finding a root cause or otherwise), then that would change the risk equation balanced by this gene. This gene could then be turned off, the effect of which would be unabated rejuvenation of body organs, leading to indefinite lifespan.
  • by Xichekolas (908635) on Friday September 08, 2006 @02:01AM (#16064422)
    Who the hell modded the parent down? That was totally on topic... just because your creator is a vengeful old dude in white robes and mine is the divine embodiment of my favorite meal doesn't mean it was off topic!
  • by Steeltoe (98226) on Friday September 08, 2006 @04:46AM (#16064803) Homepage
    Unfortunately, caloric restriction only raises the life expectancy of rodents in the laboratory, not when exposed to natural conditions. While it reduces risk of cancer, it also drastically reduces the effectiveness of the immune system at fighting off infection (and the resulting stresses which, in turn, re-raise the cancer risk.)

    This has been known for decades by those educated in food & nutrition science. Unfortunately, the news has apparently not spread widely in other fields.


    It all depends how you do it:

    http://www.genomenewsnetwork.org/articles/2004/07/ 09/calorierestriction.php [genomenewsnetwork.org]

    I am following a lakto-ovo vegetarian lifestyle myself, and can't really say that I'm missing flesh at all. Combine it with drinking lots of water, and your body will become VERY healthy. You will notice the difference within weeks.

    However, key to a good diet is enough proteins. Too many young girls start eating only pizza, salads, pasta, etc. and get malnutrition as a result from going "veggie". A veggie-diet without enough proteins and variation is no veggie-diet in my book. Correct veggie recepees have been used for thousands of years in the East, based on the Vedic Science of Ayur-veda (knowledge about life).

    Btw, what is the point of extending your lifetime, if you're miserable? Quality time, living here and now, is much more important than the length of your life - which is only fear of something so natural as death.
  • by wulfhound (614369) on Friday September 08, 2006 @07:14AM (#16065136)
    Interesting point of view, but perhaps a bit optimistic:- human lifespan is already up at the top of the range for mammals -- even if the 'turning knob' can be fixed (double or triple the maximum cell division count, and suitably increase the metabolic / nutritional budget for tumor suppression to compensate), our evolutionary line has had an upper limit of a hundred years or so since the earliest mammals evolved 100m years ago -- nothing that we've evolved in that time has built for multi-century endurance. I'd wager that it'd be substantially easier to extend the life of a rat to 20 years, or a dog to 50, than to get a human being to 200.
  • Re:Cancer, aging. (Score:4, Interesting)

    by Fordiman (689627) <fordiman@gmGIRAF ... minus herbivore> on Friday September 08, 2006 @09:27AM (#16065622) Homepage Journal
    "Sounds to me like Planned obsolescence... that is, if you believe in a higher power."

    You don't have to believe in a higher power for that. Sounds to me like a natural function of the balance between being able to repair yourself and exploding into a ball of disorganized meat (ie: developing cancer in every cell). Based on the amount of damage your body takes, it automatically determines how much it needs to be able to redivide its cells.

    "Why is it that back in Biblical times, people like Abraham & Moses used to live several hundred years? Did they all have cancer? (Assuming that cancer is an anti-aging program)"

    Nah. I would guess it's because of a trans-generational game of 'rumour' that happened before any of it got written down. Don't get me wrong; much of Exodus actually happened (the plagues, parting, etc, are easily explained by a volcano eruption that happened as moses returned to Egypt; I can't blame him for using it as a way to extort pharoh and reinforce judaism - we all have our agendas, after all, and they're almost always good in our eyes). But Genesis... it all sounds a bit like stories passed from father to son that eventually got written out.

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