Restoration of energy homeostasis by SIRT6 extends healthy lifespan.

ABSTRACT: Aging leads to a gradual decline in physical activity and disrupted energy homeostasis. The NAD⁺-dependent SIRT6 deacylase regulates aging and metabolism through mechanisms that largely remain unknown. Here, we show that SIRT6 overexpression leads to a reduction in frailty and lifespan extension in both male and female B6 mice. A combination of physiological assays, in vivo multi-omics analyses and ¹³C lactate tracing identified an age-dependent decline in glucose homeostasis and hepatic glucose output in wild type mice. In contrast, aged SIRT6-transgenic mice preserve hepatic glucose output and glucose homeostasis through an improvement in the utilization of two major gluconeogenic precursors, lactate and glycerol. To mediate these changes, mechanistically, SIRT6 inc

SUBMITTER: Roichman A 

PROVIDER: S-EPMC8163764 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature