Calorie Restriction Promotes Mammalian Cell Survival by Inducing the SIRT1 Deacetylase

TLDR

Cell loss over time is a major cause of aging, and in yeast caloric restriction delays aging by activating the Sir2 deacetylase. SIRT1 deacetylates Ku70, which sequesters Bax away from mitochondria and blocks stress‑induced apoptosis. CR induces SIRT1 expression in rats and human cells—a response dampened by insulin and IGF‑1—and this upregulation promotes long‑term survival of irreplaceable cells, potentially extending lifespan.

Abstract

A major cause of aging is thought to result from the cumulative effects of cell loss over time. In yeast, caloric restriction (CR) delays aging by activating the Sir2 deacetylase. Here we show that expression of mammalian Sir2 (SIRT1) is induced in CR rats as well as in human cells that are treated with serum from these animals. Insulin and insulin-like growth factor 1 (IGF-1) attenuated this response. SIRT1 deacetylates the DNA repair factor Ku70, causing it to sequester the proapoptotic factor Bax away from mitochondria, thereby inhibiting stress-induced apoptotic cell death. Thus, CR could extend life-span by inducing SIRT1 expression and promoting the long-term survival of irreplaceable cells.