Tumor-suppressing Gene Contributes to Aging

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."

Comments

Cancer, aging.

[sporkme]

"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.

What springs to mind...

[Meccanica]

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.)

Re:Old news...

[juushin]

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.

Re:Hmm.

[ozmanjusri]

Wonder what the catch is.

There is only one catch and that is Catch-22, which specifies that turning off p16INK4a for one's safety of your organs in the face of dangers that are real and immediate will cause cancer. Giving yourself cancer is not the process of a rational mind.

The trick might be to turn off the expression of the gene temporarily to rejuvenate aging organs, then switch it back in again to suppress cancer. That way, maybe Yossarian can have is cake and eat it too...

Re:I think they're just hyping this with that titl

[RsG]

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).

Age mutations versus cell division mutations

[qaffle]

As organisms get older the chance that they will have a mutation that leads to some form of cancer grows (in a if every day you have the chance of something happening, after enough days go by you're likely to have had it happening sense).

Does the same thing apply to a cell?

In other words, as a cell ages is it more likely to have a cancerous mutation? And how does this likeliness compare to the chance of having a cancerous mutation through a cell's reproduction process? (these are for the biologists out there)

If you have a greater chance to have the mutation a cell reproduces then you'd want cells to live along time so they have to reproduce less. If you have a greater chance as the cell sticks around (ages) then you'd want more reproduction and a shorter life span (even though this would be less energy and resource efficient, but maybe more efficient than fixing/killing cancerous cells).

Re:Age mutations versus cell division mutations

[Anonymous Coward]

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.

Genetic Safeguards are way more important...

[tempest69]

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.

Storm

Slight mischaractarization

[Ungrounded Lightning]

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.

Cancer cure == indefinite lifespan?

[Slashdiddly]

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.