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Tumor-suppressing Gene Contributes to Aging 145

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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  • Cancer, aging. (Score:4, Informative)

    by sporkme ( 983186 ) * on Thursday September 07, 2006 @09:51PM (#16063646) Homepage
    "I don't think aging is a random process - it's a program, an anti-cancer program,"
    Cancer, then, is an anti-aging program.

    The article basically states that when they turned off the flow of ink-4, embyyonic stem cells were free to divide without check. The mice without the ability to produce ink-4 developed cancer within a year and died. This behavior cannot be reliably reproduced in aged stem cells, and ink-4 production naturally increases exponentially with age.

    The main news I see here is either a possible avenue for cancer research, or a good supporting argument to lift bans on exploiting new strains of embryonic stem cells (over adult stem cells). This does not represent a specific breakthrough, but yet another amazing revelation of stem cell capabilites has come to light.

    I support the ban on cloning, I disagree with the ban on new stem cells, I am relatively opposed to mass abortion, but banning it would be stupid. I think this story's new information supports these views.
  • Re:Old news... (Score:5, Informative)

    by juushin ( 632556 ) on Thursday September 07, 2006 @10:13PM (#16063726)
    No, it is different. In the story a year ago, a korean group found that if you suppress telomerase in cancer cells--an enzyme that makes cells 'immortal' by continually adding repeats of bases on to the ends of chromosomes--the cells die. the summary on the slashdot page is not exactly correct--telomerase is not an enzyme specific to cancer cells. 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." it is a fundamentally different story and is interesting.
  • by tempest69 ( 572798 ) on Thursday September 07, 2006 @11:36PM (#16063997) Journal
    Higher organisms have genetic safeguards that are stopping cancer ALL THE TIME. Generally multiple systems in a cell need to fail before cancer can begin.

    The first thing that needs to fail is the proofreading enzymes, so that a gene or two are damaged without being repaired.

    Then the "self destruct" needs to fail to activate in a cell, The self destruct is almost always armed and ready to go, unless it gets knocked out by a "lucky" mutation.

    Even if the self destruct fails, the cell sensing needs to fail in order to grow beyond a few cells. Then the telemorase halting needs to fail in order for the cancer to reach something larger than a mole.

    The immune system is a last resort, and not a very good one in comparison.


  • by not-enough-info ( 526586 ) <> on Thursday September 07, 2006 @11:49PM (#16064031) Homepage Journal
    One key mistake in the parent's summary: Ink-4 limits the ability of adult stem cells to divide. The article suggests a theory that because damaged adult stem cells are prevented from dividing by Ink-4, unchecked tumor growth (cancer) is averted later in life.

    How this supports embryonic stem cell research is: we now have evidence that adult stem cells will not be effective when used as treatment because they will be naturally suppressed. Thus to get stem cells that will divide and provide therapy, we must use embryonic cells.
  • by Ungrounded Lightning ( 62228 ) on Friday September 08, 2006 @12:53AM (#16064221) Journal
    "There is no free lunch -- we are all doomed," Dr. Sharpless said. But he quickly modified his comment by noting that a calorically restricted diet is one intervention that is known to increase lifespan and reduce cancer, at least in laboratory mice.

    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.

    So while there is a strategy that reduces both of these TWO problems, it does it at the cost of creating a third. Again no free lunch.

    Though there may be useful insights from the lab results, life extention strategies based on caloric restriction in the real world seem unlikely to be successful.
  • by reverseengineer ( 580922 ) on Friday September 08, 2006 @12:55AM (#16064232)
    No, this has nothing to do with telomeres, which is what I think you're talking about. The product of the gene p16-Ink4a is a protein which inhibits an enzyme called a cyclin-dependent kinase. What this cyclin-dependent kinase does is control a "checkpoint" between two stages in a cell's life cycle. A cell at this checkpoint can either be told to go ahead and replicate its own DNA, or it can be told to just sort of "pause." Due in large part to the action of this gene, p16-Ink4a, most of your adult cells are stuck in "pause."

    Your body maintains enough cell division activity to do upkeep, but obviously, there are limits to that- the slow deteriorations of age, as well as the inability to make certain repairs. If p16-Ink4a is not there to inhibit its target, the kinase it inhibits will give the "go-ahead" to the cell to replicate its chromosomes, divide, return to that checkpoint, replicate, divide, and so on. If the several cell systems whose function it is to notice this alarming occurence fail in their task (your cells have genes which try to initiate suicide in the cell if an error is detected), then the cell divides out of control- cancer. This is at the very beginning of a cancer, and all happening inside the tumor cell- the rest of your body is not on alert yet. Basically, if p16-Ink4a is working correctly, it prevents cells from ever becoming cancer in the first place. The relationship to stem cells is quite interesting as well- through the action of this gene, your body essentially makes the decision that as you age, keeping around active stem cells to maintain your tissues is not worth the increased risk of cancer they represent.

  • by Anonymous Coward on Friday September 08, 2006 @10:53AM (#16066291)
    It's called antagonistic pleiotropy py []. The fitness curve at it's simplest has a central maximum, and drops off towards the extremes. The location of the maximum will depend on a number of things - for one examination see pdf [] (page down to the start of the article)
  • by reverseengineer ( 580922 ) on Friday September 08, 2006 @01:00PM (#16067299)
    The mechanism (or set of mechanisms) is a limit on how many times a non-gamette cell may replicate.

    This is known as the Hayflick limit, and is related to what the great-grandparent post brought up- telomeres. When normal differentiated cells divide, an issue with the way our DNA polymerase works causes a bit off the end of the DNA strand to not be replicated- your DNA gets shorter with each cell division. To counter this, there are sequences of repeating nucleotides at the end called telomeres. The telomeres are there to take the hit for your genes- with each replication, it is they, rather than coding regions of DNA, that get clipped.

    As you might imagine, though, this process cannot continue indefinitely; eventually, the telomeres are clipped down to nothing, and genetic damage occurs with each division, quickly making cells no longer viable. The Hayflick limit for differentiated human cells is in the range of 50-70 cell divisions. This represents the sort of tradeoff the parent post mentions- it means adult cells cannot continuously be replenished by healthy new cells, but OTOH acts as a sort of brake on cancer- a cell that is permanently stuck in "replicate and divide" mode can reach this limit in a matter of days. So, why do we get cancer anyway? The cancer cells that go on to cause havoc are ones that have found ways around this limit. One way (the most common) of doing this is by using an enzyme called telomerase. Telomerase is a specialized type of reverse transcriptase that basically writes telomere sequences back onto the chromosome, lengthening them again.

    Why don't we have this incredibly useful enzyme? We do, but the gene for it is inactivated in our differentiated cells. Cancer cells that make use of telomerase require a mutation to remove the inactivation. Or, they can simply arise from the cells which have active telomerase- stem cells. Now, a lot has been learned about the amazing properties of stem cells in the last few years, and because of their remarkable talent for repairing and rebuilding tissues, it seems very strange that your body doesn't really want many of them around- the task of the gene being mentioned here . The reason for this, as this new research suggests, may be cancer.

    It may be instructive to look at the brain- for decades, it was believed that neurons didn't even get replaced at all, and it has been only in the last few years that the idea of neurogenesis from adult stem cells has been accepted. Given the seriousness of brain injury and deterioration, it would seem as though the brain would have plenty of stem cells available to repair damage. However, brain tumors are of course incredibly deadly- the five year outlook for a glioblastoma multiforme patient is about three percent. Glioblast- that's the precursor cell for the glial cells that make up most of the brain. Basically, if the body lets cells divide, it opens itself to the possibility that those cells will divide uncontrollably. So your genes are set up to make a tough bargain- you don't have enough multipotent cells available to reverse the ravages of age or certain forms of injury, but by limiting cell division as much as it is possible, your genes limit the threat cancer poses.

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