Cited by 452Genetics, Aging, and Longevity in Model OrganismsSirtuins and Resveratrol in MedicineDietary Effects on Health

Effects of Sex, Strain, and Energy Intake on Hallmarks of Aging in Mice

Open access
Mitchell, Sarah J., Madrigal-Matute, Julio, Scheibye-Knudsen, Morten, Fang, Evandro, Aon, Miguel, González-Reyes, José A., Cortassa, Sonia, Kaushik, Susmita +39 more·2016·Cell Metabolism

Abstract

Calorie restriction (CR) is the most robust non-genetic intervention to delay aging. However, there are a number of emerging experimental variables that alter CR responses. We investigated the role of sex, strain, and level of CR on health and survival in mice. CR did not always correlate with lifespan extension, although it consistently improved health across strains and sexes. Transcriptional and metabolomics changes driven by CR in liver indicated anaplerotic filling of the Krebs cycle together with fatty acid fueling of mitochondria. CR prevented age-associated decline in the liver proteostasis network while increasing mitochondrial number, preserving mitochondrial ultrastructure and function with age. Abrogation of mitochondrial function negated life-prolonging effects of CR in yeast and worms. Our data illustrate the complexity of CR in the context of aging, with a clear separation of outcomes related to health and survival, highlighting complexities of translation of CR into human interventions.

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Crossref · 10.1016/j.cmet.2016.05.027

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Research works printed but not linked: 2

  1. Liao CY Rikke BA Johnson TE Gelfond JA Diaz V Nelson JF 2011b Fat maintenance is a predictor of the murine lifespan response to dietary restriction Aging Cell 10 629 639 21388497 PMC3685291
  2. Yuan R Tsaih SW Petkova SB Marin de Evsikova C Xing S Marion MA Bogue MA Mills KD Peters LL Bult CJ 2009b Aging in inbred strains of mice: study design and interim report on median lifespans and circulating IGF1 levels Aging Cell 8 277 287 19627267 PMC2768517

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Authors
Mitchell, S. J., Madrigal-Matute, J., Scheibye-Knudsen, M., Fang, E., Aon, M., González-Reyes, J. A., Cortassa, S., Kaushik, S., Gonzalez-Freire, M., Patel, B., Wahl, D., Ali, A., Calvo-Rubio, M., Burón, M. I., Guiterrez, V., Ward, T. M., Palacios, H. H., Cai, H., Frederick, D. W., Hine, C., Broeskamp, F., Habering, L., Dawson, J., Beasley, T. M., Wan, J., Ikeno, Y., Hubbard, G., Becker, K. G., Zhang, Y., Bohr, V. A., Longo, D. L., Navas, P., Ferrucci, L., Sinclair, D. A., Cohen, P., Egan, J. M., Mitchell, J. R., Baur, J. A., Allison, D. B., Anson, R. M., Villalba, J. M., Madeo, F., Cuervo, A. M., Pearson, K. J., Ingram, D. K., Bernier, M., & de Cabo, R.
Affiliations
  • National Institutes of Health (US)
  • University of Córdoba (ES)
  • Albert Einstein College of Medicine (US)
  • University of Pennsylvania (US)
  • Harvard University (US)
  • University of Graz (AT)
  • University of Alabama (US)
  • University of Southern California (US)
  • The University of Texas at San Antonio Health Science Center (US)
  • Pennington Biomedical Research Center (US)
Venue
Cell Metabolism
Publisher
Elsevier BV
Published
2016-06
Volume
23
Issue
6
Pages
1093-1112
ISSN
1550-4131 (ISSN-L)
OpenAlex
W2421296032
Cited by
451
References
117
Citations by year
2026: 28 · 2025: 37 · 2024: 45 · 2023: 51 · 2022: 56 · 2021: 57 · 2020: 44 · 2019: 38 · 2018: 50 · 2017: 37 · 2016: 8
FWCI
23.89
Type
journal article
Language
en
Open access
Locations
  • Cell Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Deposito Digital UFV (Francisco de Vitoria University) (submittedVersion, cc-by-nc-nd)
  • DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
  • Repository of Digital Objects for Teaching Research and Culture (University of Valencia) (submittedVersion, other-oa)
Funders
  • American Diabetes Association (1-15-MI-03)
  • Austrian Science Fund (P 24381, P 27893, I1000, P29203)
  • Bundesministerium für Wissenschaft, Forschung und Wirtschaft
  • National Institutes of Health (AG031782, AG038072)
  • National Institute on Aging (AG-04-3483, P01AG034906, R01AG043483, P01AG031782, AG031782, P30AG038072, AG038072, P30AG013319, ZIAAG000368)
  • National Institute of General Medical Sciences (R01GM090311)
  • National Institute of Diabetes and Digestive and Kidney Diseases (P30DK041296, P30DK020541, R01DK098656, P30DK079626)
  • National Institute of Environmental Health Sciences (R01ES020812, P30ES013508)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
  • Health Sciences › Medicine › Physiology › Dietary Effects on Health
Keywords
caloric restriction, aging, sex differences, mouse strains, lifespan extension, healthspan, mitochondrial function, fatty acid metabolism, mitochondrial ultrastructure, metabolomics, gene expression changes
MeSH terms
Aging, Animals, Autophagy, Energy Intake, Female, Gene Expression Regulation, Glucose, Homeostasis, Hydrogen Sulfide, Islets of Langerhans, Liver, Longevity, Male, Mice, Inbred Strains, Mitochondria, Phenotype, Sex Characteristics, Biomarkers, Cluster Analysis, Gene Expression Profiling, Ubiquitin, Caloric Restriction, Proteasome Endopeptidase Complex, Mice, Metabolomics, Metabolome

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