Energy balance
Calorie restriction extends lifespan and improves metabolic health in mammals by upregulating SIRT1 and SIRT3, which deacetylate and activate metabolic enzymes and transcription factors to shift cells from glycolysis to oxidative phosphorylation.
Calorie restriction (reducing intake to 60-70% of ad libitum levels) activates sirtuins (SIRT1 and SIRT3), which shift metabolism from glycolysis to oxidative phosphorylation, improving insulin sensitivity and extending lifespan in mice. While direct application to humans requires more research, the mechanism suggests that metabolic flexibility and mitochondrial health are key to longevity.
Sirtuins were initially found to slow aging in lower organisms and more recently shown to mediate many effects of calorie restriction on metabolism and longevity in mammals.
Why this rating
Strong genetic evidence (knockouts and transgenics) in mice, though primarily mechanistic review rather than a single clinical trial.
Source
Sirtuins, Aging, and Metabolism
Leonard Guarente · Cold Spring Harbor Symposia on Quantitative Biology · 2011
DOI 10.1101/sqb.2011.76.010629
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