Sir2-Independent Life Span Extension

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Sir2-Independent Life Span Extension by Calorie Restriction in Yeast.

Kaeberlein M, Kirkland KT, Fields S, Kennedy BK.

Departments of Genome Sciences and Medicine, University of

Washington, Seattle, Washington, United States of America.

PLoS Biol. 2004 Aug 24;2(9):E296.

Calorie restriction slows aging and increases life span in many

organisms. In yeast, a mechanistic explanation has been proposed

whereby calorie restriction slows aging by activating Sir2. Here we

report the identification of a Sir2-independent pathway responsible

for a majority of the longevity benefit associated with calorie

restriction. Deletion of FOB1 and overexpression of SIR2 have been

previously found to increase life span by reducing the levels of

toxic rDNA circles in aged mother cells. We find that combining

calorie restriction with either of these genetic interventions

dramatically enhances longevity, resulting in the longest-lived yeast

strain reported thus far. Further, calorie restriction results in a

greater life span extension in cells lacking both Sir2 and Fob1 than

in cells where Sir2 is present. These findings indicate that Sir2 and

calorie restriction act in parallel pathways to promote longevity in

yeast and, perhaps, higher eukaryotes.