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.

Now, molecular geneticists at the University of Southern California suggest that SIR2 instead promotes aging.

Their study, "Sir2 Blocks Extreme Life-Span Extension," appears in the Nov. 18 edition of the biology journal Cell. The lead author is Valter Longo, assistant professor in the Leonard Davis School of Gerontology and the USC College of Letters, Arts and Sciences.

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, Longo said, 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.

Longo proposes that 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. Organisms usually enter this mode in response to starvation.

The long-lived organisms in Longo's experiment showed extraordinary resilience under stress.

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Contact: Carl Marziali
marziali@usc.edu
213-740-4751
University of Southern California
17-Nov-2005