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Potentially Universal Mechanism Of Aging Identified
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Posted 2008-11-29, 10:29 AM
Researchers have uncovered what may be a universal cause of aging, one that applies to both single cell organisms such as yeast and multicellular organisms, including mammals. This is the first time that such an evolutionarily conserved aging mechanism has been identified between such diverse organisms.

The mechanism probably dates back more than one billion years. The study shows how DNA damage eventually leads to a breakdown in the cell's ability to properly regulate which genes are switched on and off in particular settings.

Like 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.

This research was funded by the National Institutes of Health, and the Glenn Foundation for Medical Research. David Sinclair is a consultant to Genocea, Shaklee and Sirtris, a GSK company developing sirtuin based drugs.


Source: http://www.sciencedaily.com/releases...1126122203.htm
"Stephen Wolfram is the creator of Mathematica and is widely regarded as the most important innovator in scientific and technical computing today." - Stephen Wolfram

Last edited by Chruser; 2008-11-29 at 10:33 AM.
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Posted 2008-11-29, 10:36 AM in reply to Chruser's post "Potentially Universal Mechanism Of..."
Interesting, though it's my personal opinion that humans don't need a longer life span.
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Posted 2008-11-29, 10:48 AM in reply to Jessifer's post starting "Interesting, though it's my personal..."
man the first thing that probley ages are scars and i have a lot of them
Tim
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deal w/ them
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Posted 2008-11-29, 09:49 PM in reply to Jessifer's post starting "Interesting, though it's my personal..."
Jessifer said: [Goto]
Interesting, though it's my personal opinion that humans don't need a longer life span.
Personally I wouldn't mind living for a few thousand years.














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Posted 2008-11-29, 10:23 PM in reply to D3V's post starting "Personally I wouldn't mind living for a..."
I say only those who have the potential of advancing the human race in a positive direction be able to live so long.

You would not qualify, Dev.
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Posted 2008-11-29, 10:40 PM in reply to Jessifer's post starting "I say only those who have the potential..."
Who's to judge that I cannot advance the human race in a positive direction? Blasphemy.














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Posted 2008-11-30, 06:16 PM in reply to D3V's post starting "Who's to judge that I cannot advance..."
What do you have to give to the advancement of the human race, exactly?
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Posted 2008-11-30, 06:22 PM in reply to Jessifer's post starting "What do you have to give to the..."
What, possibly, does any one person attribute to the human race? I have not yet unleashed any of my potential and it is yet to be determined if I will have a positive of negative effect on this world we live in. I'd love to work on a patent for a perpetual motion device that would be beneficial in our world in the future when anti-gravity scenarios would become more apparent.

I'm sure my over exaggerated imagination with simplistic everday events could be studied somehow in the future. So why not?














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Posted 2008-11-30, 06:42 PM in reply to D3V's post starting "What, possibly, does any one person..."
Everyone has the potential to give something to the human race, whether it be positive or negative. Does that mean everyone should have an extended life?
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Posted 2008-11-30, 06:46 PM in reply to Jessifer's post starting "Everyone has the potential to give..."
Jessifer said: [Goto]
Everyone has the potential to give something to the human race, whether it be positive or negative. Does that mean everyone should have an extended life?
Everyone should have an equal opportunity. I think this should turn into a debate thread.














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!King_Amazon!: I talked to him while he was getting raped
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Posted 2008-11-30, 06:49 PM in reply to D3V's post starting "Everyone should have an equal..."
Who should the judges be? Randy, Paula, and Simon?

Actually, now that I think on that...I'd watch it.

Last edited by Jessifer; 2008-11-30 at 06:51 PM.
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Posted 2008-11-30, 06:50 PM in reply to Jessifer's post starting "Everyone has the potential to give..."
So we can all be elves off of Lord of the Rings. ownage.
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Posted 2008-11-30, 07:10 PM in reply to Jessifer's post starting "Who should the judges be? Randy, Paula,..."
Jessifer said: [Goto]
Who should the judges be? Randy, Paula, and Simon?

Actually, now that I think on that...I'd watch it.
I don't think anyone should be able to judge it, lol. That's my whole point, everyone that qualifies for whatever "treatment" that allows you not to age should be able to judge for themselves if they want to live an extended life or not.














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!King_Amazon!: I talked to him while he was getting raped
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Posted 2008-11-30, 07:12 PM in reply to D3V's post starting "I don't think anyone should be able to..."
Realistically, there'd have to be some sort of screening.
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Posted 2008-11-30, 07:14 PM in reply to Jessifer's post starting "Realistically, there'd have to be some..."
I figure anything that would rule you out would already be present in our juducial system. Convicted felons, multiple offenders, shit like that.














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Posted 2008-11-30, 07:17 PM in reply to D3V's post starting "I figure anything that would rule you..."
I think that there should be more to it than that...
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Posted 2008-11-30, 07:31 PM in reply to Jessifer's post starting "I think that there should be more to it..."
Like what really? Something like this would be the ultimate step towards utopia. I'm sure we would evolve an elaborate system of natural selection being that people are living much longer, but who knows.














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Posted 2008-11-30, 08:55 PM in reply to D3V's post starting "Like what really? Something like this..."
Injecting Sirtuin into someone to allow them to live longer doesn't exactly sound "natural".
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Posted 2008-11-30, 10:54 PM in reply to Jessifer's post starting "Injecting Sirtuin into someone to allow..."
Yes; however, if we were to be injecting bodies with this over time we would become accustomed to it.














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Posted 2008-12-01, 09:15 AM in reply to D3V's post starting "Yes; however, if we were to be..."
So our bodies being forced to adapt to something unnatural would, in turn, be natural?

I think if that were to be the case then, humans having extended lives, that there would have to be some form of population control as well. If not, in the end I could see the human race becoming something like a parasite, not that we aren't already on some level.
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