NatureOct 9, 2024

How limited food intake affects health and lifespan in genetically varied mice

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Feb 27, 2026

Abstract

of 40% significantly extended lifespan in 960 female mice.

Both caloric restriction and resulted in lifespan extension proportional to the degree of dietary restriction.
Genetics had a larger influence on lifespan than dietary restriction, with lifespan being heritable.
Key traits associated with lifespan included stress resilience, immune function, and body composition metrics.
40% caloric restriction led to significant lifespan extension but resulted in a loss of lean mass and potential increased infection susceptibility.
Intermittent fasting was ineffective in extending lifespan for mice with higher body weight prior to the intervention.
Metabolic changes from dietary restriction, such as reduced body fat and lower fasting glucose levels, were not linked to increased lifespan.

Simplified

extends healthy lifespan in multiple species. , an alternative form of dietary restriction, is potentially more sustainable in humans, but its effectiveness remains largely unexplored. Identifying the most efficacious forms of dietary restriction is key for developing interventions to improve human health and longevity. Here we performed an extensive assessment of graded levels of caloric restriction (20% and 40%) and intermittent fasting (1 and 2 days fasting per week) on the health and survival of 960 genetically diverse female mice. We show that caloric restriction and intermittent fasting both resulted in lifespan extension in proportion to the degree of restriction. Lifespan was heritable and genetics had a larger influence on lifespan than dietary restriction. The strongest trait associations with lifespan included retention of body weight through periods of handling-an indicator of stress resilience, high lymphocyte proportion, low red blood cell distribution width and high adiposity in late life. Health effects differed between interventions and exhibited inconsistent relationships with lifespan extension. 40% caloric restriction had the strongest lifespan extension effect but led to a loss of lean mass and changes in the immune repertoire that could confer susceptibility to infections. Intermittent fasting did not extend the lifespan of mice with high pre-intervention body weight, and two-day intermittent fasting was associated with disruption of erythroid cell populations. Metabolic responses to dietary restriction, including reduced adiposity and lower fasting glucose, were not associated with increased lifespan, suggesting that dietary restriction does more than just counteract the negative effects of obesity. Our findings indicate that improving health and extending lifespan are not synonymous and raise questions about which end points are the most relevant for evaluating aging interventions in preclinical models and clinical trials. 1 2-8 9

Key numbers

36.3%

Increase in Median Lifespan

Comparison of median lifespan between 40% and ad libitum feeding groups.

9 months

Lifespan Extension by Diet

Median lifespan increase for 40% vs. ad libitum feeding.

7.78×10

Mortality Doubling Time

Estimated mortality doubling time from Gompertzian lifespan models.

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How limited food intake affects health and lifespan in genetically varied mice

Abstract

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