In honor of the pending acquisition of Sirtris by GlaxoSmithKline — and the advent of truly big pharma getting into the biology of aging — I wanted to pay tribute to SIRT1, the principal target of the sirtuin activators under development.
SIRT1 plays a variety of roles in regulatory biology and lifespan determination, and the list is growing: it inhibits p53, blocks inflammatory signaling, extends the healthspan of mice, and improves exercise tolerance It slices, it dices, and that’s not all: SIRT1 also
- regulates energy metabolism and mediates lifespan extension in response to calorie restriction (CR);
- directs neurogenesis;
- suppresses tumorigenesis in the gut (and, in tumors that do form, may negatively regulate the oncogenic form of β-catenin);
- antagonizes cellular senescence (though, just as with inhibiting p53, this might not be a crazy good idea in in all tissues);
- gives Lenny Guarente something to write reviews about; and
- has some really interesting relatives, including SIRT6, which was recently shown to maintain telomeric chromatin in a healthy and functional state.
Watch for more functional news, as well as novel connections between SIRT1 functions and human disease, as industry starts generating more (and more specific) activators of this multi-talented protein and its relatives.