Cited by 501Genetics, Aging, and Longevity in Model OrganismsDietary Effects on HealthAnimal Behavior and Reproduction

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Genetic variation in the murine lifespan response to dietary restriction: from life extension to life shortening

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Liao, Chen‐Yu, Rikke, Brad A., Johnson, Thomas E., Diaz, Vivian, Nelson, James F.·2010·Aging Cell

DOI 10.1111/j.1474-9726.2009.00533.xPMC PMC3476836

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Abstract

Summary: Chronic dietary restriction (DR) is considered among the most robust life‐extending interventions, but several reports indicate that DR does not always extend and may even shorten lifespan in some genotypes. An unbiased genetic screen of the lifespan response to DR has been lacking. Here, we measured the effect of one commonly used level of DR (40% reduction in food intake) on mean lifespan of virgin males and females in 41 recombinant inbred strains of mice. Mean strain‐specific lifespan varied two to threefold under ad libitum (AL) feeding and 6‐ to 10‐fold under DR, in males and females respectively. Notably, DR shortened lifespan in more strains than those in which it lengthened life. Food intake and female fertility varied markedly among strains under AL feeding, but neither predicted DR survival: therefore, strains in which DR shortened lifespan did not have low food intake or poor reproductive potential. Finally, strain‐specific lifespans under DR and AL feeding were not correlated, indicating that the genetic determinants of lifespan under these two conditions differ. These results demonstrate that the lifespan response to a single level of DR exhibits wide variation amenable to genetic analysis. They also show that DR can shorten lifespan in inbred mice. Although strains with shortened lifespan under 40% DR may not respond negatively under less stringent DR, the results raise the possibility that life extension by DR may not be universal.

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Authors: Liao, C., Rikke, B. A., Johnson, T. E., Diaz, V., & Nelson, J. F.
Affiliations: The University of Texas at San Antonio Health Science Center (US)
University of Colorado Boulder (US)
Corresponding author: Nelson, James F.
ORCID: Liao, Chen‐Yu
Johnson, Thomas E.
Diaz, Vivian
Nelson, James F.
Venue: Aging Cell
Publisher: Wiley
Published: 2010-01-11
Volume: 9
Issue: 1
Pages: 92-95
ISSN: 1474-9718 (ISSN-L)
1474-9726
DOI: 10.1111/j.1474-9726.2009.00533.x
PMC: PMC3476836
OpenAlex: W2104438296
Cited by: 501
References: 26
Citations by year: 2026: 19 · 2025: 25 · 2024: 25 · 2023: 24 · 2022: 32 · 2021: 34 · 2020: 39 · 2019: 33 · 2018: 30 · 2017: 31 · 2016: 41 · 2015: 39 · 2014: 30 · 2013: 31 · 2012: 21
FWCI: 6.86
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Aging Cell (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute on Aging (R01AG024354)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Health Sciences › Medicine › Physiology (medical) › Dietary Effects on Health
Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Animal Behavior and Reproduction
Keywords: dietary restriction, lifespan, genetic variation, recombinant inbred mouse strains, lifespan extension, lifespan reduction, dietary intake, female fertility, sex differences in lifespan, genetic determinants of aging
MeSH terms: Animals, Female, Life Expectancy, Longevity, Male, Mice, Inbred Strains, Sex Characteristics, Genetic Variation, Caloric Restriction, Mice

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Genetic variation in the murine lifespan response to dietary restriction: from life extension to life shortening

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