Restoration of energy homeostasis by SIRT6 extends healthy lifespanpost by DirectedEvolution (AllAmericanBreakfast) · 2021-06-05T21:11:49.729Z · LW · GW · 1 comments
This is just a link post for an article that came out in Nature on May 28th. Open access.
“ SIRT6 overexpression in C57BL mice led to a 27% and 15% extension in median lifespan, in males and females, respectively (p = 7.1 × 10−6 and 1.1 × 10−6). Likewise, in comparison to their WT littermates, SIRT6 overexpression induced a 11% and 15% extension in maximal lifespan in males and females, respectively (p = 0.007 and 0.001). Similarly, SIRT1 + 6-tg mice exhibited a 25% and 20% extension in median lifespan (p = 1.1 × 10−6 and 1.2 × 10−8), and 13% and 15% extension in maximal lifespan (p = 0.01 and 0.001), in males and females, respectively. Relative to WT littermates, overexpression of SIRT1 alone did not affect median or maximal lifespan, in accordance with previous data.”
“ Here, we show that male and female C57BL/6JOlaHsd mice overexpressing SIRT6, but not SIRT1, live significantly longer than WT littermates. SIRT6-tg mice maintain young-like physical activity and metabolic flexibility, along with reduced aging-related pathologies. Moreover, further analyses showed that old SIRT6-tg mice show a young-like liver metabolite profile. Notably, SIRT6 enables energy production under limited energy conditions, such as fasting and aging. To mediate this function, SIRT6 promotes hepatic β-oxidation, lactate and glycerol shuttling and hepatic utilization, NAD+/NADH ratio in the liver, and glycerol release from adipose tissue. These SIRT6-regulated metabolic pathways coordinate to maintain young-like TCA cycle and GNG activities in old age (Fig. 7e). Thus, the positive effect of SIRT6 on healthy lifespan is strain and sex independent and requires SIRT6 regulation of energy production in at least two sites, liver and adipose tissues. Together, this emphasizes the potential of SIRT6-based therapeutic approaches in addressing age-related frailty and other diseases.”
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