The sirtuin pathway refers really to a family of cellular proteins that are highly conserved among species. The pathway when activated appears to reduce aging. They act as master cellular switches which in response to certain environmental triggers can turn on or off a wide array of protein actors.
Sirtuins are activated by resveratrol and caloric restriction.
In the current study researchers sought to determine the importance of Sirt6 in regulation of endothelial cell aging. Endothelial cells line passage in the body, including blood vessels.
In the study, researchers grew cultures of human endothelial cells. They then transfected the cells with silencer RNA against Sirt6, which essentially acts to completely shut down Sirt6 in the cells.
It was first found the the endotheial cells naturally express Sirt6 and that levels decline with age. When Sirt6 was silenced the researchers found the cells became less able to divide and more rapidly became senescent.
It was also found that the cells lacking Sirt6 exhibited higher rates of DNA damage and telomere dysfunction without showing signs of increased oxidative stress.
The authors conclude:
The present study may have important implications in the search of strategies to counteract the
development of age-associated vascular pathologies. Studies in mice have shown that SIRT6
deficiency produces premature ageing phenotypes, whereas SIRT6 overexpression causes a
moderate increase in the lifespan of male mice.
In this context, our findings that depletion of SIRT6 in endothelial cells induces a senescent phenotype, suggest that increasing the levels or activity of this protein may be a relevant approach to delay vascular aging.