The Longevity and Metabolism Plot Thickens, Yet Again

Recent work on the biochemical and genetic roots of the healthy life extension produced by calorie restriction leads us in a new and interesting direction:

By deleting a gene that has been linked to longevity in previous studies, scientists have produced one of the longest recorded life-span extensions in any organism, and opened a new door for anti-aging research in humans.


Scientists have known for several years that an extra copy of the SIR2 gene can promote longevity in yeast, worms and fruit flies. That finding was covered widely and incorporated into anti-aging drug development programs at several biotechnology companies.


Rather than adding copies of SIR2 to yeast, Longo's research group deleted the gene altogether.

The result was a dramatically extended life span -- up to six times longer than normal -- when the SIR2 deletion was combined with caloric restriction and/or a mutation in one or two genes, RAS2 and SCH9, that control the storage of nutrients and resistance to cell damage.

Human cells with reduced SIR2 activity also appear to confirm that SIR2 has a pro-aging effect, says Longo, although those results are not included in the Cell paper.

Since all mammals share key aging-related genes, the paper points to a new direction for human anti-aging research.

SIR2 -- and possibly its counterpart in mammals, SIRT1 -- may block the organism from entering an extreme survival mode characterized by the absence of reproduction, improved DNA repair and increased protection against cell damage, Longo suggests. Organisms usually enter this mode in response to starvation.


A "really exciting" implication, Longo says, is that cells may be able to speed up their DNA repair efforts. All organisms have the ability to repair harmful mutations in their DNA, whether caused by age, radiation, diet or other environmental factors. Cancer often begins when DNA mutations outstrip a cell's ability to remain differentiated.

Many researchers believe DNA repair systems are already running flat out. The organisms in Longo's experiment say otherwise.

The first caveat is that this research takes place in yeast - a great deal of good work comes from yeast studies, but there are as many differences as similarities between yeast and mammalian biochemistry. That said, this is most interesting, given the radical life extension achieved in this study - matching some of Cynthia Kenyon's worm experiments. I predict that we'll be hearing results of the same or similar sets of genetic tweaks in nematode worms and flies within a year.

The supposition on DNA repair is indeed exciting - but much more work needs to happen in this field in order to discover whether any form of significant healthy life extension technologies reside in the realm of tinkering with genes and metabolism in higher mammals. Given the size and longevity of whales, one would suppose there to be room for improvement for humans in there somewhere.

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Eh, "characterized by the absence of reproduction"? Does this mean that deleting this gene will make you sterile?

Posted by: Brock at November 18th, 2005 6:04 AM
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