R EPORTS
release of cytochrome c. Downstream events
include caspase activation and cleavage of
Calorie Restriction Promotes poly(ADP-ribose) polymerase (PARP). Un-
der normal conditions, Bax is rendered inac-
Mammalian Cell Survival by tive in the cytoplasm by its tight association
with Ku70, a DNA repair factor (20, 21). In
Inducing the SIRT1 Deacetylase response to acute cell damage or stress, two
critical lysines in Ku70 (K539, K542) be-
Haim Y. Cohen,1 Christine Miller,1 Kevin J. Bitterman,e acetylated by the acetyltransferases
Nathan R. Wall,1 Brian Hekking,1 Benedikt Kessler,1 CBP and PCAF, and the Ku70-Bax interac-
Konrad T. Howitz,2 Myriam Gorospe,3 Rafael de Cabo,4 tion is disrupted, allowing Bax to localize to
mitochondria and initiate apoptosis (21).
David A. Sinclair1*
Given the role of yeast Sir2 in life-span
extension by CR (2), we investigated whether
A major cause of aging is thought to result from the cumulative effects of cell mammalian SIRT1 might also be involved in
loss over time. In yeast, caloric restriction (CR) delays aging by activating the the CR response. Tissues were extracted from
Sir2 deacetylase. Here we show that expression of mammalian Sir2 (SIRT1) is 12-month-old rats that had either been fed ad
induced in CR rats as well as in human cells that are treated with serum from libitum (AL) or a CR diet (60% of
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