Sirtuins have been shown to regulate life-span in response to nutritional availability. We show here that levels of the mammalian sirtuin, SIRT6, increased upon nutrient deprivation in cultured cells, in mice after fasting, and in rats fed a calorie-restricted diet. The increase in SIRT6 levels is due to stabilization of SIRT6 protein, and not via an increase in SIRT6 transcription. In addition, p53 positively regulates SIRT6 protein levels under standard growth conditions but has no role in the nutrient-dependent regulation of SIRT6. These observations imply that at least two sirtuins are involved in regulation of life-span by nutrient availability.
Bibliographical noteFunding Information:
We thank Doron Ginsberg (Bar-Ilan University, Israel) and members of the Cohen lab for helpful comments on the manuscript; Fred Alt (HMS) for the SIRT6 −/− mice; Moshe Oren (Weizmann Institute, Israel) for the p53 −/− mice; and Izumi Horikawa (NIH) for pcDNA-DEST40-SIRT6. This study was supported by grants from the Israeli Academy of Sciences, German–Israeli Foundation, Binational US–Israel Foundation, Israel Cancer Association, Koret Foundation, and the Israel Cancer Research Foundation. H.C. is funded by the Alon Foundation.
- Calorie restriction
- Nutrient availability