Researchers identify a potentially universal mechanism of aging
November 26, 2008Like our current financial crisis, the aging process might also be a product excessive deregulation. Researchers have discovered that DNA damage decreases a cell's ability to regulate which genes are turned on and off in particular settings. This mechanism, which applies both to fungus and to us, might represent a universal culprit for aging.
"This is the first potentially fundamental, root cause of aging that we've found," says Harvard Medical School professor of pathology David Sinclair. "There may very well be others, but our finding that aging in a simple yeast cell is directly relevant to aging in mammals comes as a surprise."
These findings appear in the November 28 issue of the journal Cell.
For some time, scientists have know that a group of genes called sirtuins are involved in the aging process. These genes, when stimulated by either the red-wine chemical resveratrol or caloric restriction, appear to have a positive effect on both aging and health.
Nearly a decade ago, Sinclair and colleagues in the Massachusetts Institute of Technology lab of Leonard Guarente found that a particular sirtuin in yeast affected the aging process in two specific ways—it helped regulate gene activity in cells and repair breaks in DNA. As DNA damage accumulated over time, however, the sirtuin became too distracted to properly regulate gene activity, and as a result, characteristics of aging set in.
"For ten years, this entire phenomenon in yeast was considered to be relevant only to yeast," says Sinclair. "But we decided to test of this same process occurs in mammals."
Philipp Oberdoerffer, a postdoctoral scientist in Sinclair's Harvard Medical School lab, used a sophisticated microarray platform to probe the mammalian version of the yeast sirtuin gene in mouse cells. The results in mice corroborated what Sinclair, Guarente, and colleagues had found in yeast ten years earlier.
Oberdoerffer found that a primary function of sirtuin in the mammalian system was to oversee patterns of gene expression (which genes are switch on and which are switch off). While all genes are present in all cells, only a select few need to be active at any given time. If the wrong genes are switched on, this can harm the cell. (In a kidney cell, for example, all liver genes are present, but switched off. If these genes were to become active, that could damage the kidney.) As a protective measure, sirtuins guard genes that should be off and ensure that they remain silent. To do this, they help preserve the molecular packaging—called chromatin—that shrink-wraps these genes tight and keeps them idle.
The problem for the cell, however, is that the sirtuin has another important job. When DNA is damaged by UV light or free radicals, sirtuins act as volunteer emergency responders. They leave their genomic guardian posts and aid the DNA repair mechanism at the site of damage.
During this unguarded interval, the chromatin wrapping may start to unravel, and the genes that are meant to stay silent may in fact come to life.
For the most part, sirtuins are able to return to their post and wrap the genes back in their packaging, before they cause permanent damage. As mice age, however, rates of DNA damage (typically caused by degrading mitochondria) increase. The authors found that this damage pulls sirtuins away from their posts more frequently. As a result, deregulation of gene expression becomes chronic. Chromatin unwraps in places where it shouldn't, as sirtuin guardians work overtime putting out fires around the genome, and the unwrapped genes never return to their silent state.
In fact, many of these haplessly activated genes are directly linked with aging phenotypes. The researchers found that a number of such unregulated mouse genes were persistently active in older mice.
"We then began wondering what would happen if we put more of the sirtuin back into the mice," says Oberdoerffer. "Our hypothesis was that with more sirtuins, DNA repair would be more efficient, and the mouse would maintain a youthful pattern gene expression into old age."
That's precisely what happened. Using a mouse genetically altered to model lymphoma, Oberdoerffer administered extra copies of the sirtuin gene, or fed them the sirtuin activator resveratrol, which in turn extended their mean lifespan by 24 to 46 percent.
"It is remarkable that an aging mechanism found in yeast a decade ago, in which sirtuins redistribute with damage or aging, is also applicable to mammals," says Leonard Guarente, Novartis Professor of Biology at MIT, who is not an author on the paper. "This should lead to new approaches to protect cells against the ravages of aging by finding drugs that can stabilize this redistribution of sirtuins over time."
Both Sinclair and Oberdoerffer agree with Guarente's sentiment that these findings may have therapeutic relevance.
"According to this specific mechanism, while DNA damage exacerbates aging, the actual cause is not the DNA damage itself but the lack of gene regulation that results," says Oberdoerffer. "Lots of research has shown that this particular process of regulating gene activity, otherwise known as epigenetics, can be reversed—unlike actual mutations in DNA. We see here, through a proof-of-principal demonstration, that elements of aging can be reversed."
Recent findings by Chu-Xia Deng of the National Institute of Diabetes, Digestive and Kidney Diseases, has also found that mice that lack sirtuin are susceptible to DNA damage and cancer, reinforcing Sinclair's and Oberdoerffer's data.
Citation: Cell, November 28, 2008 Volume 135, Issue 6
Source: Harvard Medical School
Oct 16, 2009 |
not rated yet |
0
Like it or not, after you had your chance to produce offspring your role is to die and make room for the next generation.
This kind of research is obviously good for the group that wants to live longer, it is very important indeed.
And I feel very sad when I see old photos/movies of those extraordinary people who died decades/centuries ago. Such a waste.
Did I state you should accept your fate?
I am not telling you to die, I am telling you that your organism *is programmed* to die.
Aging is not just some malfunction which can be easily fixed it is a complex developmental program which works exactly as intended by evolution.
The only reason we don't die much faster is that this program is of low priority and in natural environment predators and diseases took care to finish us off quickly.
The cells could easily keep us alive much longer, but that is not desirable from evolutionary point of view. It is much better to mate quickly and die as it leads to faster evolution and higher chances of survival in the ever changing environment.
One proof that aging and death are not just malfunctions is the presence of apoptosis - a programmed cell death - in unicellular organisms like baker's yeast. This is a perfect example that (from evolutionary perspective) it makes more sense to breed and die then to live forever.
BTW do you realize that if we finally find ways to significantly extend human life it will surely lead to a global conflict?
Everyone will want to live longer, but the Earth wont be able to support us all.
For example if it were now possible to cheaply extend average lifetime to 3 times its current values human population would at least triple.
That assumes current birthrates could be kept but with all that extra time people would actually want to have more offspring.
All this will lead to extreme social pressures and in all probability another global conflict.
Eventually all breeding will be strictly regulated with no more then 1 children per person per lifetime. To have more you will need to buy the rights from others.
with is no more then a deases a genetic program
i fu want that done in ur lifetime join him
http://www.mprize.com
Sez who?
Again, sez who? This article seems to directly contradict you. So the question becomes: what is your source of authority to make this declaration with such certainty? Because you say so? Not good enough.
A. Latest News: A Potentially Universal Mechanism Of Aging
http://www.eureka...1908.php
"Researchers have discovered that DNA damage decreases a cell's ability to regulate which genes are turned on and off in particular settings. This mechanism, which applies both to fungus and to us, might represent a universal culprit for aging. "
B. Universal mechanism of aging has been explained earlier...
Predicting Chronological And Physiological Age Is Complicated
http://www.the-sc...age#1077
Genes Are Organisms And Age, Too...
http://www.the-sc...page#900
Dov Henis
(A DH Comment From The 22nd Century)
http://blog.360.y...Q--?cq=1
Good catches; my scientific and critical erudition suggests that it may come from a "blind reader" of Richard Dawkins' works -- works of pure Evolutionism, a neo-Darwinist rhetorical reductionism -- the Dawkinsian Scientism of the 20th century par excellence originated from the Oxford University (since the publication of his first book "The Selfish Gene" in 1976)!?
Best wishes, Mong 11/27/8usct12:49p; author "Decoding Scientism" and "Consciousness & the Subconscious" (works in progress since July 2007), "Gods, Genes, Conscience" (2006: www.iuniverse.com...95379907 ) and "Gods, Genes, Conscience: Global Dialogues Now" (blogging avidly since 2006: http://www2.blogg...50569778 ).
eh? I think that there is a lot more to it than that. Biologically, there is no need for you to die to "make room for the next generation".
What about the human brain that has EVOLVED to solve problems. One of those problems would be how to live longer, in order to pass along the knowledge of survival to as many succeeding generations as possible. That gives those generations a better chance to succeed themselves.
A lot of us agree with you that death is mandated by evolution (an immortal species could never evolve through natural selection, since "selection" requires that the un-selected die.)
But I think the point gmurphy was trying to make is: who gives a ^&%# what evolution mandates? We will have the power to override it. And, yes, exercising that power may cause a host of problems -- overpopulation, famine, war, etc. But we'll do it anyway; you *know* we will. ;-)
You can debate the wisdom of eliminating aging, but you cannot debate its inevitability. Whether a hundred years from now or a thousand, at some point in the future aging will exist only among those who choose it. And I'd wager there will be strict population controls.
I very strongly agree with almost everything you said -- except this part. It sounds like you are confusing "non-aging" with "unkillable". Even non-aging beasties will die, just not from old age. It might slow down the evolutionary process, but that's all.
I've never read anything Dawkins wrote, if anyone deserves credit its Charles Darwin, the rest is pretty stightforward.
Sez who?
hah hah. Very ironic. However, it's not a symmetrical situation. Presumably, you are posting comments because you want to convince people of your POV (I suppose I could be wrong on that, but then why...). If you argue in a non-convincing manner, for instance by simply making adamant imperative statements, you're basically wasting electrons.
I on the other hand, wasn't trying to convince you of anything -- merely trying to point out that *you* have failed to be convincing. Thus, not symmetrical.
I am not trying to convince people I only provide another perspective to counter the popular view presented in the press namely that aging is deregulation or just damage accumulation.
Either the explanation makes sense to you or it doesn't my authority is not relevant.
This would not work as quite often it is resources that limit population growth not predators or diseases. In such a situation an organism without programmed death would compete with his own offspring which would naturally give incentive to produce weaker offspring and in turn quickly lead to evolutionary dead end. Aging and death are required for evolution to work well.
There is a well defined optimal lifespan which depends both on organism and its environment, thats why a mouse will live up to 5 years while a whale can exceed 200. Both are mammals, so their cells have to be very similar yet their longevity is so much different.
Our cells have the capacity to live very long, but instead they choose to die early to better their evolutionary success.
In fact cancer can be seen as cells rebelling against this "groupthink" and refusing to die, choosing instead to focus on their own good to the detriment of the organism as a whole.
(This should not be taken too literally of course, cells are not humans)
Limited resources impose that need. Even if we assume its not true for humans now it has been during most of our evolution so this assumption is "built into" us and all other life.
Once your children reach sexual maturity it should be them breeding not you otherwise you will be competing with them. Once you don't breed and are done with bringing up your offspring your time is up.
While the real reason for aging might not matter for most of you it should for those who are serious about trying to find the solution. Understanding the problem is the first step to solving it.
Did Darwin research and/or write about "aging" and "death" in his lifetime?
Or are you just one of the neo-Darwinists -- like Dawkins -- when he was challenged with a specific "gene" theory question, he would run away by taking a cover under Darwinism!?
Sez who? -- please see my recent analyses here: http://www.physfo...pic=6365]http://www.physfo...pic=6365[/url]]http://www.physfo...pic=6365[/url]&view=findpost&p=381089 (October 12, 2008); here: http://www.physfo...pic=6365]http://www.physfo...pic=6365[/url]]http://www.physfo...pic=6365[/url]&view=findpost&p=339579 (May 11, 2008) and here: http://www.physfo...pic=6365]http://www.physfo...pic=6365[/url]]http://www.physfo...pic=6365[/url]&view=findpost&p=330762 (April 7, 2008) -- I listed the dates of my posts, in case these specific URL links are to be truncated by this entry field herein.
Best wishes, Mong, author "Decoding Scientism" and "Consciousness & the Subconscious" (works in progress since July 2007), "Gods, Genes, Conscience" (2006: www.iuniverse.com...95379907 ) and "Gods, Genes, Conscience: Global Dialogues Now" (blogging avidly since 2006: http://www2.blogg...50569778 ).
Best wishes, Mong 11/29/8usct2:06p; author "Decoding Scientism" and "Consciousness & the Subconscious" (works in progress since July 2007), "Gods, Genes, Conscience" (2006: www.iuniverse.com...95379907 ) and "Gods, Genes, Conscience: Global Dialogues Now" (blogging avidly since 2006: http://www2.blogg...50569778 ).
Actually, I think he is posting because he DISAGREES with YOUR POV.
I think Evolution is a process that goes on in the natural world, but it isn't any more of an obstacle to us than any other process in nature.
After all, if we go by the logic that unnatural things shouldn't exist, then we need to tear down all our skyscrapers, get rid of computers, live in caves and hunt animals with spears.
Aging is one more thing people can eliminate as a danger to ourselves. If we ever manage to get off the planet with its limited resources, who cares about overpopulation?
Just look att Da Vinci, this guy died before he could finish all his ideas, he would certanily contribute from an extension of his life.
You confused who said what.
In this scenario more then 3 trillion people die of starvation within a year.
Also making wild guesses about things you have no idea about has nothing to do with being intelligent or analytical, to the contrary in fact.
The same kind of thinking saw us colonizing the Solar System by year 2000.
We have no clue how aging works, just some very vague leads. Besides finding how it works is the easy part, tweaking live humans to make necessary changes is incomparably more challenging. So it might take 10 years or it might take 100 years, or it might prove completely impractical.
No, I did, but my views are based on Darwin's brilliant Theory of Evolution so I am happy to give him credit, its one of the most powerful frameworks ever developed by humans.
I don't know or care what neo-Darwinism stands for, I also don't appreciate people who have to label others first in order to comprehend what they have to say.
If you want to add something to the discussion just type it (or copy it) instead of quoting random posts.
And the links will be broken if you edit your post after posting it.
Maybe more money should be spent on helping people LIVE, rather than just staying alive longer.
The US government has distorted the economy in so many ways. Maybe bad regulations would be a better descriptor.
But if these things will cost as much as your ordinary vitamin supplement, then we have a problem...
Regarding overpopulation, birth restriction is the most likely solution. It would slow down growth enough so that, eventually, people will live off planet.
Well, first of all you got the attributions wrong. *I* said that, not him. Secondly, it's difficult to see how he could disagree with my POV when he posted first, and the post you referenced was in response to that. Perhaps he's psychic?
Are you a gerontologist or geriatrist in training?
How could Darwinism of the 19th century be related to Gerontology of the 20th century?
Aren%u2019t your statements about Aging and Death self-contradictory to those raised by D666 (and also commented by me) before?
Versus
Furthermore,
1] If you are a 'true' scientist (biologist or gerontologist), how could you not care about neo-Darwinism vs. Darwinism?
The way you presented your case (Aging, Death, Darwinism, etc) reminded me (and/or other readers) of Dawkinsism that I have had recently analyzed: As Richard Dawkins is a pseudo-scientist, a neo-Darwinist or Darwinian reductionist or fundamentalist or dogmatist par excellence at Oxford (UK)!
2] No, I didn't edit the long URL links after posting them; I just noticed that the PhysOrg.com has been recently decoupled and incompatible with that of the PhysForum.com (although they may be still run by the same Administration)!?
If you are interested -- even if you're not a neo-Darwinist -- you should read what I have to say about Dawkinsism vs. Darwinism in those PhysForum.com posts that I referenced above.
Best wishes, Mong 12/1/8usct2:28p; author "Decoding Scientism" and "Consciousness & the Subconscious" (works in progress since July 2007), "Gods, Genes, Conscience" (2006: www.iuniverse.com...95379907 ) and "Gods, Genes, Conscience: Global Dialogues Now" (blogging avidly since 2006: http://www2.blogg...50569778 ).
Jeez, more labels. Why do you have to know my specialty? What difference does it make?
I explained above how, the theory of evolution is what my arguments are based on. While in its modern form it might differ somewhat from what was first proposed by Darwin its still him who deserves most credit.
No, they are not contradictory. We have no clue how aging works *on molecular level* but the fact that we are products of evolution implies, and I tried to explain above how, that we have a program which actively regulates our lifespan, and that it is not just an accumulation of passive errors.
The situation is analogous to not knowing the details of how a particular engine works but still being able to predict its maximal efficiency solely from thermodynamic principles.
The details may vary but the descriptive power of thermodynamics allows us to make predictions which will hold anyway.
The same holds for evolution and biology, molecular biology is bound by evolution so we can make inferences even without knowing all the details.
I don't care about labels, but since you question my scientific integrity I had to look it up.
I agree with modern evolutionary synthesis as explained in the section of article linked below, if thats what you mean by neo-Darwinism then yes, I completely agree with it.
http://en.wikiped...ynthesis
Depending how the "gene" is defined I may or may not agree with Dawkins' view that "gene is the only true unit of selection".
In my view all information passed between generations which can be replicated is subject to natural selection in its broadest sense (although the vast majority of it has no effect).
However this is a broader sense that is usually assumed when talking about this subject, if we restrict ourselves to biology then both DNA, RNA, proteins (prion like ones) and other as yet unidentified elements which can self propagate can serve as "genes" and undergo natural selection.
That said only DNA and in a few rare cases RNA seems to play a significant role in life as we know it so the rest can be ignored.
So does this title apply to me too now?
Should I feel bad about being a neo-Darwinist?
Just editing the post that contains links after posting it will brake the links. The links are not properly copied into the edit window once you hit edit, thats what breaks them.
I checked one of those post but was unable to find anything concerning this topic, once again if you want to add something just type it or copy it here.
While it may solve overpopulation problem to some extent it will certainly lead to extreme social tensions.
Faced with a choice between death and measures which although drastic might significantly prolong your life the choice is simple.
The privileged class will have to take extreme measures to protect themselves so the social landscape won't be pretty and democracy might not make it.
Totally agree. I wonder how the society would actually react, maybe the reaction wouldn't be so dramatic after all.
Its not really a comparable situation.
Those are well isolated areas where most of the people don't even realize there are cures for their ailments and where solutions are way out of their reach.
Here, on the other hand, we are talking about a modern society where you are perfectly aware that there are those privileged, who can live and enjoy life, while you, who worked hard all your life, have to die. Now add to this that you have a loving family which counts on you, children who you want to see grow up, and million other reasons to live. You won't accept your fate calmly, in all probability you will do whatever it takes to get the money for the treatment, especially when faced with time of your death approaching as there won't be much to loose anyway.
Now imagine millions of people in such a situation, I certainly see it leading to extreme social tensions.