cron-web.org

[A1CR]

In this 2004-06-18 post, MR notes new evidence that expression of the SIRT1 signaling gene is increased in CR'ed rats, as well as in human cells exposed to the serum from CR'ed rats, and that insulin attenuates this increase in gene experssion.

The paper MR points to also talks about how SIRT1 might be causally involved in the longevity benefits of CR. A viable CR mimetic may be closer than we think...

For anyone who's been following the Sir2/sirtuin/SIRT1 story, the
abstract should be self-explanatory; for anyone who hasn't been: search
the Archives at the CR Society.

http://www.sciencemag.org/cgi/content/abstract/1099196

Published online 17 June 2004

[DOI: 10.1126/science.1099196]

Calorie Restriction Promotes Mammalian Cell Survival by Inducing the
SIRT1 Deacetylase

Haim Y. Cohen, Christine Miller, Kevin J. Bitterman, Nathan R. Wall,
Brian Hekking, Benedikt Kessler, Konrad T. Howitz, Myriam Gorospe,
Rafael de Cabo, David A. Sinclair

... In yeast, caloric restriction (CR) delays aging by activating the
Sir2 deacetylase.

Here we show that expression of mammalian Sir2 (SIRT1) is induced

--> in CR rats as well as

--> in human cells that are treated with serum from these animals.

Insulin and insulin-like growth factor 1 (IGF-1) attenuated this response.

SIRT1 deacetylates the DNA repair factor Ku70, causing it to sequester
the pro-apoptotic factor Bax away from mitochondria, thereby inhibiting
stress-induced apoptotic cell death. Thus, CR could extend life-span by
inducing SIRT1 expression and promoting the long-term survival of
irreplaceable cells.

------------------

Good news for sirtuin-based CR-mimetic drugs -- and supplements, if
someone can work out the bugs with resveratrol ...

-MR