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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!
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
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.
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.
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.
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.
There's a famous principle in Mathematics & Quantum Mechanics, first discovered by the British mathematician GH Hardy, and then refined by Heisenberg, which states that both a function & its Fourier transform cannot decay too rapidly [otherwise the function is identically zero].
Or, as Mic Jagger put it: You can't always get what you want.
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 think you fail to understand the possibilities of having multiple avenues for the body to prevent unchecked cellular reproduction. Built into each cell should be the codings to tell it how and how often to divide, and at what stages of life. When those checks fail due to any number of circumstances (mutations due to environment or flawed genes), a secondary check, the immune system, responds to a threat of unchecked cellular reproduction by destroying it if possible.
Think of it like social behavior. Ideally, all pro-social behavior is internalized and you operate within the guidelines of the law. However, when you fail to (speeding, for instance), law enforcement is there to step you back into the proper action.
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).
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>
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.
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.
"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.
Bantam Dominique roosters crow a four-note song. Once you've heard it as "Happy BIRTHday" you can't NOT hear it that way
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.
"FDA staff reviewers expressed concern about the number of patients who were left out of the study because they died."
Okay. A few problems with your thinking:
:)
1) Those old people are generally able to end their own lives if they really wanted to - but they don't. Your generalisation that old people "don't want to live" is inaccurate. Many studies (check on PubMed with a few salient keywords) have shown that elderly people are just as happy (if not more so) than younger people. There is also no magic point at which people suddenly decide that life is not worth living - the vast majority of people will always want to live longer.
2) Health and medical inequities. These will always exist, but that isn't a reason to suddenly stop with progression of science and medicine. There is actually a trickle-down effect, where medical procedures that are pioneered and used in developed countries become available to poorer areas of the world. One major example is the use of antibiotics and vaccines which have done more to prevent childhood mortality across the world than any other technological advance. If we stopped research into new medical advances, it doesn't mean that all the money will suddenly be used to treat the poor and less fortunate. This is a false dichotomy.
3) Anti-ageing research will not result in infirm and sick people kept in that condition for decades. The whole point to anti-ageing research is to increase the health and quality of life of people as they age. We won't have a situation where people age to 70-80, are in poor condition and then stay like that for another 40-50 years. The aim is to have 80 year olds who are as healthy as 50 year olds (or less!), and centenarians who act like they are healthy 60 year-olds. With successful progress in anti-ageing research we will actually decrease the health cost of the elderly, freeing up more money in the health system to treat other medical problems.
In summary: This is a good thing, and it IS thinking about quality of life, as well as quantity - they are directly linked, there need not be a choice of one or the other.
(Disclaimer: I just submitted my PhD last month on ageing processes in rats, so I have a pretty informed opinion on this topic
No, your parent post deliberately sidestepped the Gambler's Fallacy. He clearly indicated that he meant "more likely" in the sense of "the odds of at least one tails after one flip is 50%; the odds of at least one tails after 8 flips is 99.6%", since the total number of tails/mutations accumulates. After a very long time, the probability of one or more mutations is nearly certain, even if the probability of each mutation occuring is constant.
Range Voting: preference intensity matters
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.)
/ 09/calorierestriction.php
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
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.
http://www.debunkingskeptics.com/
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.