Research

Hormonal

Calorie restriction extends lifespan in model organisms and mammals, and this extension requires the NAD-dependent deacetylase activity of sirtuins (specifically Sir2/SIRT1).

Calorie restriction promotes longevity, but it works through specific biological mechanisms involving sirtuins. While the paper focuses on mechanisms, the implication is that maintaining metabolic health and NAD levels is key. For humans, this suggests that dietary patterns mimicking calorie restriction (like intermittent fasting) might activate these pathways, though direct lifespan extension in humans is not yet proven.

GoodSupportsHIGH confidence
Sir2 is required for lifespan extension by CR in yeast, worms, and flies... In yeast, CR (0.5% glucose), was previously shown to increase mitochondrial function and to up-regulate SIR2 activity... A more severe CR regimen (0.05% glucose) extends yeast replicative lifespan by a different mechanism that is apparently independent of both SIR2 and mitochondrial respiration.
Marcia C. Haigis et al. · Genes & Development · 2006

Why this rating

Strong evidence from multiple model organisms (yeast, worms, flies, mice) and human population studies linking SIRT3 to longevity.

Source

Mammalian sirtuins—emerging roles in physiology, aging, and calorie restriction

Marcia C. Haigis et al. · Genes & Development · 2006

DOI 10.1101/gad.1467506

narrative_reviewCited 1,296×
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DOI resolved against Crossref · corpus check 2026-06-10

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