Slashdot Mirror
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."
"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.
FairTax baby!
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.)
You live and learn. At least, you live.
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.
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.
The heavens do not fall for such a trifle.
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).
Erotic is when you use a feather. Exotic is when you use the whole chicken.
Yes, when cancer works, you stop getting older.
Q.E.D.
This issue is a bit more complicated than you think.
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).
So it sounds like The Designer of the Universe [a pretty intelligent Fellow, from what I hear] may have placed the very same restrictions on the stuff He created on Day 5 as He did on the stuff He created way back on Day 1.
I forget, was it spaghetti or ramen he created on Day 5?
- These characters were randomly selected.
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
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.
---k--
</stupid>
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.
Bantam Dominique roosters crow a four-note song. Once you've heard it as "Happy BIRTHday" you can't NOT hear it that way
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.
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!
Self-referential Sigs are cool on /. these days...
54
Actually, the majority is almost always conservative, no matter what generation you consider. We have had rather few progressive Presidents, wouldn't you say? Didn't matter whether the boomers were young or old. The Boomers were too young to vote for Kennedy. The choice in 1964 was between Goldwater, who wanted to expand the war in Vietnam, and Johnson, who claimed he didn't, but did. Johnson was a fluke. Nobody knew he had a liberal social policy agenda, he was a conservative Southern democrat who Kennedy put on the ticket in order to win Texas. After Johnson we elected Nixon, by landslides, just when the boomers started voting en mass. Then we chose Carter, a conservative, religious southern Democrat, over the half-dead Jerry Ford, hardly a progressive choice. Then 12 years of Reagan and Bush I -- our most conservative Presidents since Hoover -- during the prime years of 30-something Boomer voting! 8 years of Clinton, who cut welfare to the bone and accomplished nothing on any progressive agenda. Then 8 years of (gack) Bush II.
John Stuart Mill said, "I never meant to say that the Conservatives are generally stupid. I meant to say that stupid people are generally Conservative. I believe that is so obviously and universally admitted a principle that I hardly think any gentleman will deny it." Mill goes on to say that since there are undeniably a lot of stupid people, the Conservatives will always be a very powerful party. Perhaps this is closer to the explanation you are looking for.