SIRT1
SIRT1 (sirtuin 1) is an NAD+-dependent protein deacetylase. Its activity depends on the NAD+/NADH ratio, which makes it responsive to the fasting and low-energy state.
Function
The NAD+/NADH ratio rises during calorie restriction and exercise, and SIRT1 activity follows. Its substrates include histones (H4K16ac in particular), p53 (deacetylation dampens p53-driven arrest and apoptosis), FOXO transcription factors (deacetylation changes their stress-response output), PGC-1α (activating mitochondrial biogenesis), and NF-κB (deacetylation reduces inflammatory transcription). The combined output resembles calorie restriction: reduced growth signaling, increased mitochondrial function, increased stress resistance, reduced inflammation.
In aging and cancer
SIRT1 activation is the proposed mechanism of the resveratrol hypothesis - resveratrol activates SIRT1
Log in and become a supporter to read the full article.
Become a supporter to read the full article.