Caloric restriction

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Sustained reduction of energy intake, typically by twenty to forty percent, without malnutrition. It is the oldest and most reproducible lifespan-extending intervention in laboratory animals: Clive McCay's group at Cornell reported in 1935 that restricted rats lived substantially longer than freely fed controls, and the result has been repeated across yeast, nematodes, flies and rodents for ninety years. It is also the clearest case of a result that did not survive translation cleanly. Two long-running rhesus macaque studies gave opposite answers — the Wisconsin National Primate Research Center reported reduced age-related mortality in 2009, the National Institute on Aging reported no significant survival benefit in 2012 — and the 2017 joint reanalysis attributed the difference to diet composition, age at onset and how the control animals were fed, meaning the Wisconsin controls may have been effectively overfed. In humans the CALERIE trial demonstrated feasibility and cardiometabolic benefit over two years, with no lifespan data and no prospect of any.

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