sir2-independent life span extension by calorie restriction in yeast卡路里限制sir2-independent寿命延长的酵母.pdfVIP

Open access, freely available online PLoS BIOLOGY Sir2-Independent Life Span Extension by Calorie Restriction in Yeast 1 2 1,3 2* Matt Kaeberlein , Kathryn T. Kirkland , Stanley Fields , Brian K. Kennedy 1 Departments of Genome Sciences and Medicine, University of Washington, Seattle, Washington, United States of America, 2 Department of Biochemistry, University of Washington, Seattle, Washington, United States of America, 3 Howard Hughes Medical Institute, University of Washington, Seattle, Washington, United States of America 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. Citation: Kaeberlein M, Kirkland KT, Fields S, Kennedy BK (2004) Sir2-independent life span extension by calorie restriction in yeast. PLoS Biol 2(9): e296. Introduction consistent with the idea that Sir2 and Fob1 bo