Research

Hormonal

Calorie restriction extends lifespan and delays age-related diseases through a regulated neuroendocrine and metabolic response (involving SIR2/SIRT1 and insulin/IGF-1 signaling) rather than merely reducing the mechanical accumulation of oxidative or glycation damage.

Calorie restriction works by signaling your body to shift into a maintenance mode, not just by burning fewer calories. This involves lowering insulin and growth hormone levels, which triggers cellular repair pathways (like SIRT1). To leverage this, focus on reducing caloric intake moderately (25-60% below ad libitum) to trigger these hormonal shifts, rather than extreme fasting which may not sustain the steady-state benefits observed in studies.

ModerateQualifiesMEDIUM confidence
The important lesson from the yeast studies is that the extension in life span by CR is not a mechanical consequence of a reduction in ROS or AGE. Rather, the extension is a regulated response requiring SIR2.
Jana Koubova et al. · Genes & Development · 2003

Why this rating

The paper is a perspective/review proposing a speculative model based on yeast and worm data extrapolated to mammals; direct mechanistic proof in humans is lacking.

Source

How does calorie restriction work?

Jana Koubova et al. · Genes & Development · 2003

DOI 10.1101/gad.1052903

narrative_reviewCited 456×
Read the paper
DOI resolved against Crossref · corpus check 2026-06-10

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