Restoration of energy homeostasis by SIRT6 extends healthy lifespan

Sirtuins have received much attention in recent years for their lifespan-increasing potential, and for their link to resveratrol, a compound found in red wine that has shown beneficial effects against cancer, heart disease, and inflammation in animal studies.

sirtuin 6 (SIRT6), a key orchestrator of lipid, glucose, and inflammation responses, based largely on the work of Professor Haim Cohen, initially at Harvard University and now at Bar Ilan University in Tel Aviv. SIRT6 suppresses triglyceride synthesis, fat metabolism, and inflammation (by suppressing NF-kB and other pathways), as well as glycolysis.

Professor Cohen's lab, along with others, has shown that transgenic overexpression of SIRT6 leads to restoration of "youthful" energy homeostasis, improved metabolic profiles, and significantly prolonged lifespan in mice.

One study indicates that "The NAD+-dependent SIRT6 deacetylase 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."

Furthermore, specific deletion of SIRT6 in mouse liver induces marked alterations in gene expression, leading to increased triglyceride synthesis, reduced ß-oxidation of fatty acids, increased glycolysis, and fatty liver formation.

In the livers of patients with NASH, other forms of progressive liver dysfunction, paracetamol overdose, and other diseases, markedly lower levels of SIRT6 are found. SIRTLab has demonstrated that elevation of SIRT6 levels using its technology normalizes the macroscopic and histological appearance of the liver, improves liver function tests, and reverses the progression of fatty liver.

A therapeutic role for SIRT6 has also been proposed as current evidence suggests that this sirtuin is important in preserving genomic integrity when cellular damage or stress occurs. It is therefore believed that overexpression of SIRT6 may have a protective role against tumorigenesis.

Another study dictates that the Restoration of energy homeostasis by SIRT6 extends healthy lifespan. “SIRT6 plays a critical role in the occurrence and development of CVDs. SIRT6 inhibits cardiomyocyte hypertrophy, transformation of fibroblasts, formation of atheromatous plaque, and infiltration of inflammatory cells. SIRT6 ameliorates cardiac remodeling and atherosclerosis, and prevents the occurrence and development of CVDs.”