 Dietary restriction impacts health and lifespan of genetically diverse miceAndrea Di Francesco (),
Andrew G. Deighan,
Lev Litichevskiy,
Zhenghao Chen,
Alison Luciano,
Laura Robinson,
Gaven Garland,
Hannah Donato,
Matthew Vincent,
Will Schott,
Kevin M. Wright,
Anil Raj,
G. V. Prateek,
Martin Mullis,
Warren G. Hill,
Mark L. Zeidel,
Luanne L. Peters,
Fiona Harding,
David Botstein,
Ron Korstanje,
Christoph A. Thaiss,
Adam Freund and
Gary A. Churchill ()
Nature, 2024, vol. 634, issue 8034, 684-692 Abstract: Abstract Caloric restriction extends healthy lifespan in multiple species1. Intermittent fasting, an alternative form of dietary restriction, is potentially more sustainable in humans, but its effectiveness remains largely unexplored2–8. Identifying the most efficacious forms of dietary restriction is key for developing interventions to improve human health and longevity9. 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. Date: 2024 Downloads: (external link) Related works: Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:634:y:2024:i:8034:d:10.1038_s41586-024-08026-3 Ordering information: This journal article can be ordered from DOI: 10.1038/s41586-024-08026-3 Access Statistics for this article Nature is currently edited by Magdalena Skipper More articles in Nature from Nature |
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