Sirtuin activation
Category: Pathways · Last updated
Sirtuins are a family of seven mammalian NAD+-dependent class-III lysine deacylase enzymes (SIRT1–SIRT7) named after the founding Saccharomyces cerevisiae gene Sir2. They consume one molecule of NAD+ for each deacylation reaction, coupling enzymatic activity to cellular NAD+ status.
The seven sirtuins
| Sirtuin | Localization | Notable substrates |
|---|---|---|
| SIRT1 | Nucleus + cytoplasm | PGC-1α, p53, FOXO3, NF-κB |
| SIRT2 | Cytoplasm + nucleus | Tubulin, FOXO1 |
| SIRT3 | Mitochondria | SOD2, LCAD, GDH |
| SIRT4 | Mitochondria | GDH (ADP-ribosylation activity) |
| SIRT5 | Mitochondria | CPS1 (desuccinylation) |
| SIRT6 | Nucleus | Histones H3K9ac, H3K56ac |
| SIRT7 | Nucleolus | rDNA chromatin |
Activation
Sirtuin activity scales with cellular NAD+ availability. Conditions that elevate NAD+ — caloric restriction, exercise, NAD+-precursor supplementation — produce increased sirtuin activity in cell-culture and animal-model assays.
Relevance to research peptides
- NAD+ · the obligate substrate of sirtuin activity