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 increases hepatic gluconeogenic gene expression, de novo NAD+ synthesis, and systemically enhances glycerol release from adipose tissue. These findings show that SIRT6 optimizes energy homeostasis in old age to delay frailty and preserve healthy aging.

NAD+ Metabolism and Diseases with Motor Dysfunction

“…Global overexpression of Sirt6, but not Sirt1, lengthened lifespan and improved motor behavior. Sirt6 overexpression also enhanced the activity of metabolic pathways, such as gluconeogenesis, in aged mice [59].…”

Proteomic and Transcriptomic Analyses Indicate Reduced Biofilm-Forming Abilities in Cefiderocol-Resistant Klebsiella pneumoniae

“…Moreover, 38 genes were down-regulated in proteome but up-regulated in transcriptome. As shown in Figure 6E, correlation coefficient of the expressions of protein and gene were 0.44, indicating that the expression of proteins and genes were not always consistent, which is involved with many complicated factors (Roichman et al, 2021). For example, mRNA translation is also regulated by a number of factors, such as microRNA, or the precursors of the translated protein need to be modified and activated.…”

Evaluation of the Anti-Aging Effects of a Probiotic Combination Isolated From Centenarians in a SAMP8 Mouse Model

“…( 30 ) found that Sirt 6 can be recruited to the promoters of NFκB downstream genes, reducing the level of promoter acetylation and inhibiting the expression of downstream genes related to apoptosis and cellular senescence. Studies have shown that overexpression of Sirt 6 can increase the healthy lifespan of mice by an average of 30% ( 31 ), so Sirt 6 may be another mechanism by which probiotics exert anti-aging effects, although this eventuality requires further study. The detection of NeuN-positive cells, apoptosis, proliferation-related proteins, and Sirt 1 in the hippocampus demonstrated that the probiotic combination can prevent hippocampal neuronal loss ( Figure 3 ).…”