Sirt1 (silent information regulator 2 homolog 1) is a protein that in humans is encoded by the SIRT1 gene. This gene is a member of the sirtuin family, which are characterized by their NAD+-dependent deacetylase activity. SIRT1 was first identified as an Sir2 homolog in Caenorhabditis elegans and later found to be orthologous to Sir2 in other species, including Saccharomyces cerevisiae, Drosophila melanogaster, and mammals. In yeast, Sir2 regulates lifespan extension by catalyzing the removal of acetyl groups from histones and other proteins. Studies in flies and mice have shown that SIRT1 also plays an important role in regulating metabolism, stress resistance, aging, neuroprotection and longevity.
In mammalian cells, SIRT1 has been shown to regulate energy homeostasis by modulating key enzymes involved in glucose metabolism, lipogenesis and fatty acid oxidation. Additionally, SIRT1 deacetylates and activates transcription factors such as FoxO3a and PGC-1α, which are involved in regulating cellular stress response pathways. Furthermore, recent studies have demonstrated that SIRT1 can protect against age-related neurodegenerative diseases through its ability to regulate neuronal energy metabolism and synaptic plasticity genes. Overall, the evidence suggests that SIRT1 plays a pivotal role in mediating the health benefits of calorie restriction (CR) – one of the most effective interventions for delaying aging and age-related diseases – by modulating various metabolic pathways involved in CR physiology.