Potentially Universal Mechanism Of Aging Identified

By | December 1, 2008

This fits the objectives of SENS.

forever_young1Researchers 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. …

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.” …

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.”

“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. – sd

How long until we have a pill? There are obstacles.

Chris Patil notes a number of recent papers on progress towards the commercial deployment of sirtuin activators – calorie restriction mimetics, in other words – and obstacles yet in the way: “Given the current regulatory laws in the US and elsewhere, getting drugs approved as anti-aging therapies per se is difficult to say the least… – longevitym

Even better than resveratrol, we may be able to some day activate genes with RNA.

The latest twist on the Nobel prizewinning method of RNA interference, or RNAi, could prove to be a real turn-on. Whereas standard RNAi silences a target gene, switching protein production off, the new technique boosts gene activity, providing a genetic “on” switch. – ns

I liked this thought:

If one had a model of a candidate persons genome (In 10 years perhaps $1000 to sequence one persons genome) and knew more about what different genes did and then ran simulations to determine the optimal expression and suppression of those genes…I believe the result would be unlocking vastly superior athletic, intellectual performance, immune systems and longevity. If the early stage result is something approaching what we have done in mice then a fully optimized expression could be several times better. – nextbigfuture

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