Genetic dissection of dietary restriction in mice supports the metabolic efficiency model of life extension
Open accessAbstract
Dietary restriction (DR) has been used for decades to retard aging in rodents, but its mechanism of action remains an enigma. A principal roadblock has been that DR affects many different processes, making it difficult to distinguish cause and effect. To address this problem, we applied a quantitative genetics approach utilizing the ILSXISS series of mouse recombinant inbred strains. Across 42 strains, mean female lifespan ranged from 380 to 1070days on DR (fed 60% of ad libitum [AL]) and from 490 to 1020days on an AL diet. Longevity under DR and AL is under genetic control, showing 34% and 36% heritability, respectively. There was no correlation between lifespans on DR and AL; thus different genes modulate longevity under the two regimens. DR lifespans are significantly correlated with female fertility after return to an AL diet after various periods of DR (R=0.44, P=0.006). We assessed fuel efficiency (FE, ability to maintain growth and body weight independent of absolute food intake) using a multivariate approach and found it to be correlated with longevity and female fertility, suggesting possible causality. We found several quantitative trait loci responsible for these traits, mapping to chromosomes 7, 9, and 15. We present a metabolic model in which the anti-aging effects of DR are consistent with the ability to efficiently utilize dietary resources.
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Even among highly genetically similar strains of yeast or mice, dietary restriction is equally likely to shorten lifespan as to extend lifespan.
“Even among highly genetically similar strains of yeast or mice, dietary restriction is equally likely to shorten lifespan as to extend lifespan.76,77,78”
From Asynchronous, contagious and digital aging (2021) · cites this paper as [77]
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References 45 · Cited by 84
Research works printed but not linked: 1
- Merry BJ Bittle AH Collins KJ 1986 Dietary manipulation of ageing: an animal model The Biology of Human Ageing Cambridge University Press 233 242
- Authors
- Rikke, B. A., Liao, C.-Y., McQueen, M. B., Nelson, J. F., & Johnson, T. E.
- Affiliations
- University of Colorado Boulder (US)
- The University of Texas at San Antonio Health Science Center (US)
- Corresponding author
- Rikke, Brad A.
- Venue
- Experimental Gerontology
- Publisher
- Elsevier BV
- Published
- 2010-09
- Volume
- 45
- Issue
- 9
- Pages
- 691-701
- ISSN
- 0531-5565 (ISSN-L)
- PMC
- PMC2926251
- OpenAlex
- W2051945197
- Cited by
- 84
- References
- 45
- Citations by year
- 2026: 5 · 2025: 1 · 2024: 3 · 2023: 4 · 2022: 5 · 2021: 9 · 2020: 6 · 2019: 2 · 2018: 6 · 2017: 4 · 2016: 6 · 2015: 7 · 2014: 8 · 2013: 3 · 2012: 5
- FWCI
- 1.97
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Experimental Gerontology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Ellison Medical Foundation
- National Institute on Aging (R01AG024354)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD060726)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Physiology › Dietary Effects on Health
- Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Animal Behavior and Reproduction
- Keywords
- dietary restriction, lifespan extension, longevity, aging, female fertility, fuel economy, quantitative trait loci, heritability, weight maintenance
- MeSH terms
- Animals, Body Weight, Energy Intake, Diet, Reducing, Female, Fertility, Hair, Humans, Life Expectancy, Longevity, Male, Mice, Inbred Strains, Models, Biological, Rodentia, Mice
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