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Mechanism

Sirtuins (SIRT1–SIRT7)

A family of NAD+-dependent enzymes that deacetylate histones and regulatory proteins. Involved in metabolism, DNA repair, autophagy, circadian rhythm, and longevity.
Category
Scientific evidence
Moderate
Number of findings
3
Sources
Our own summaries · Cited studies

Effect by goal · level of evidence

Longevity

improves Moderate preclinical (A)
Central axis of longevity

Caloric restriction activates SIRT1 in heart muscle; fasting activates it by promoting hepatic ketogenesis.

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Heart disease

improves Moderate preclinical (A)
Cardioprotection

SIRT1 protects against heart failure by improving insulin sensitivity in the myocardium.

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Metabolism

improves Moderate preclinical (A)
Cellular energy sensor

Sirtuins regulate fatty acid oxidation, mitochondrial biogenesis, and the stress response; resveratrol, EGCG, exercise, and NAD+ precursors (NR, NMN) activate them.

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In depth

*⏱ 2 min read

Sirtuins are highly conserved enzymes that play key roles in longevity and healthy lifespan in multiple organisms; they are linked to the regulation of a variety of metabolic processes, including insulin release, lipid mobilization, the stress response, and the modulation of life expectancy; they have been implicated in the pathophysiology of metabolic disorders such as type 2 diabetes, neurological disorders such as Parkinson's disease, and many other age-related conditions.

There are seven known sirtuins in mammals, SIRT1 through SIRT7, with varied functions and different cellular locations; the most studied sirtuin, SIRT1, is the most similar to the yeast sirtuins that have been studied extensively; SIRT1 deacetylates histones and a variety of non-histone proteins to regulate gene expression, DNA repair, autophagy, apoptosis, metabolism, inflammation, circadian rhythms, and cell survival; sirtuins require NAD+ to function, which directly links sirtuin activity to NAD+ levels that decline with age.

Sirtuin activation through lifestyle

Sirtuins respond to physiological changes in energy levels and regulate energy homeostasis; caloric restriction activates SIRT1 in cardiac muscle and protects against heart failure by improving cardiac insulin sensitivity; fasting activates SIRT1, promoting hepatic fatty acid oxidation and ketogenesis, and fasting-mediated sirtuin activation improved the health and survival of rhesus monkeys subjected to caloric restriction in a long-term longevity study.

Resveratrol, a compound in red wine, activates SIRT1 in animal models and may mediate some of the cardioprotective effects of moderate red wine consumption; exercise activates SIRT1 in skeletal muscle through the activation of AMPK; EGCG from green tea and quercetin from onions and apples activate FOXO3 through sirtuin-related mechanisms; and NAD+ precursors such as NR and NMN raise the NAD+ levels available to sirtuins, potentially improving sirtuin function in tissues where NAD+ is depleted by aging.

References

  1. SIRT1 And Other Sirtuins In Metabolism. doi:10.1016/j.tem.2013.12.001
  2. Sirtuins Regulate Key Aspects Of Lipid Metabolism. doi:10.1016/j.bbapap.2009.11.021
  3. Sirtuins And Type 2 Diabetes: Role In Inflammation, Oxidative Stress. doi:10.3389/fendo.2019.00187
  4. Mitochondrial Metabolism, Sirtuins, And Aging. doi:10.1101/cshperspect.a013102
  5. Caloric Restriction Improves Health And Survival Of Rhesus Monkeys. doi:10.1038/ncomms14063
  6. Calorie Restriction Promotes Mammalian Cell Survival By Inducing SIRT4. doi:10.1126/science.1099196

Information, not medical advice. Scientific evidence reflects the quality of the studies.

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