Sirtuins
The longevity genes. Sirtuins are a family of 7 proteins (SIRT1-7) that regulate metabolism, DNA repair, inflammation, and stress response. They require NAD+ to function and decline with age. Fasting, exercise, and caloric restriction activate them.
The 7 Sirtuins
SIRT1
Most studied. Nucleus/cytoplasm. Metabolism, inflammation, stress resistance. Resveratrol target.
SIRT2
Cytoplasm. Cell cycle, metabolism. Tubulin deacetylation.
SIRT3
Mitochondrial. Energy production, ROS defense. Key for metabolic health.
SIRT4
Mitochondrial. Regulates glutamine metabolism. Less studied.
SIRT5
Mitochondrial. Ammonia detox, urea cycle. Protein modification.
SIRT6
Nuclear. DNA repair, telomeres. Overexpression extends lifespan in mice.
What Sirtuins Do
DNA Repair
Activate repair enzymes. Maintain genomic stability. SIRT1 and SIRT6 especially.
Metabolic Regulation
Shift to fat burning. Improve insulin sensitivity. Energy efficiency.
Inflammation Control
Reduce NF-κB. Lower chronic inflammation. Prevent inflammaging.
Mitochondrial Health
SIRT3 protects mitochondria. ROS management. Energy production.
Epigenetic Regulation
Histone deacetylation. Gene silencing. Maintain youthful expression patterns.
Telomere Maintenance
SIRT6 at telomeres. Prevent shortening. Cellular aging.
Activating Sirtuins
Caloric Restriction
Original discovery. 20-30% reduction. Raises NAD+/NADH ratio.
Fasting
Intermittent or extended. NAD+ rises when fasting. SIRT1 especially.
Exercise
Both cardio and resistance. NAD+ production. SIRT1 and SIRT3.
NAD+ Precursors
NMN, NR boost NAD+. Sirtuins need NAD+ to function. Declining with age.
Resveratrol
SIRT1 activator. Red grapes, wine. Works synergistically with NAD+.
Cold Exposure
Activates SIRT3. Mitochondrial biogenesis. Brown fat activation.