Restoration of energy homeostasis by SIRT6 extends healthy lifespan

Roichman A, Elhanati S, Aon MA, Abramovich I, Di Francesco A, Shahar Y · Nature Communications

The strongest mammalian sirtuin lifespan result, and it corrects an earlier one from the same group. SIRT6 overexpression extended median lifespan by 27 percent in males and 15 percent in females (p=7.1x10-6 and 1.1x10-6) and maximal lifespan by 11 and 15 percent (p=0.007 for males). The authors note that their earlier work in a mixed CB6 background had extended male lifespan only, so the sex restriction was a property of the strain rather than of the gene. Overexpressing SIRT1 did not extend lifespan. Healthspan moved with it: less frailty, preserved hepatic glucose output and normoglycaemia in old age, red cell counts and haemoglobin held at young levels, and an LDL to HDL ratio that stayed low while it rose in wild-type mice.

Population

C57BL/6JOlaHsd mice overexpressing SIRT1, SIRT6, or both, against wild-type littermates: 52 male and 50 female wild-type, 51 male and 41 female SIRT6-transgenic

Intervention

Transgenic overexpression of SIRT6

Comparator

Wild-type littermates, and SIRT1-overexpressing mice in the same experiment

Limitations

A genetic overexpression model, not a supplement: it shows that more SIRT6 activity is good for a mouse, not that raising NAD+ raises SIRT6 activity enough to matter. One strain, one laboratory. SIRT6-transgenic mice were 4 to 7 percent heavier after a year with more body fat, which the paper reports without resolving. No joint or cartilage endpoint.