EverspanLoading protein structure…
AlphaFold Confidence (pLDDT)
SIRT1
NAD⁺-Dependent Deacetylase · Class III histone deacetylase
Think of SIRT1 as your cells' master anti-aging switch. It gets activated when you fast or exercise, triggering a cascade of protective responses. The problem: it runs on NAD+, a fuel that drops by roughly half between your 20s and 60s – leaving the switch stuck in the off position. Replenishing NAD+ with NMN or NR can turn it back on.
Size
747 amino acids
Complexes
Nuclear/cytoplasmic
Key pathway
NAD⁺/Sirtuin axis
Controls
Gene silencing · Metabolism
Why SIRT1 is Central to Longevity
SIRT1 sits at the nexus of the most powerful longevity interventions – caloric restriction, fasting, and exercise all converge on raising NAD⁺ levels and activating SIRT1. Its substrates include p53 (suppressing senescence), FOXO transcription factors (activating stress resistance), and PGC-1α (driving mitochondrial biogenesis).
The age-related decline in NAD⁺ is one of the best-characterized hallmarks of aging, and supplementation with NAD⁺ precursors like NMN or NR has become one of the most actively tested longevity strategies in human trials. The logic is direct: more NAD⁺ means more SIRT1 activity means more longevity signaling.
The structure shown here was predicted by Google DeepMind's AlphaFold 2 model. Colors indicate prediction confidence (pLDDT score): blue regions are predicted with very high accuracy; orange regions represent flexible or disordered segments where confidence is lower.
Interventions Targeting SIRT1
Sorted by evidence grade
About this structure
This 3D model was generated by AlphaFold 2, developed by Google DeepMind and EMBL-EBI. The structure represents the full-length human SIRT1 protein (UniProt Q96EB6). AlphaFold predictions may differ from experimentally determined structures, particularly in disordered regions. Structure data is provided under CC BY 4.0. alphafold.ebi.ac.uk