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

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

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Mitchell, Sarah J., Madrigal-Matute, Julio, Scheibye-Knudsen, Morten, Fang, Evandro, Aon, Miguel, González-Reyes, José A., Cortassa, Sonia, Kaushik, Susmita, Gonzalez-Freire, Marta, Patel, Bindi, Wahl, Devin, Ali, Ahmed, Calvo-Rubio, Miguel, Burón, María I., Guiterrez, Vincent, Ward, Theresa M., Palacios, Hector H., Cai, Huan, Frederick, David W., Hine, Christopher, Broeskamp, Filomena, Habering, Lukas, Dawson, John, Beasley, T. Mark, Wan, Junxiang, Ikeno, Yuji, Hubbard, Gene, Becker, Kevin G., Zhang, Yongqing, Bohr, Vilhelm A., Longo, Dan L., Navas, Placido, Ferrucci, Luigi, Sinclair, David A., Cohen, Pinchas, Egan, Josephine M., Mitchell, James R., Baur, Joseph A., Allison, David B., Anson, R. Michael, Villalba, José M., Madeo, Frank, Cuervo, Ana Maria, Pearson, Kevin J., Ingram, Donald K., Bernier, Michel, de Cabo, Rafael·2016·Cell Metabolism

DOI 10.1016/j.cmet.2016.05.027PMC PMC4911707

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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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Integrated Transcriptome, Proteome, Acetylome, and Metabolome Profiling of Mouse Liver During Normal AgingPreprint
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“In metabolomics studies on aging in animals (Houtkooper et al. 2011; Mitchell et al. 2016), CR is recognized as the most effective intervention for delaying aging and promoting healthy longevity.”
Graded Calorie Restriction Causes Graded Slowing of Epigenetic Ageing in Mice
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Hepatic FGF21 Deletion Improves Glucose Metabolism, Alters Lipogenic and Chrna4 Gene Expression, and Enhances Telomere Maintenance in Aged Female Mice
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Behavioral evaluation of aging in experimental animals
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Effect of D-galactose on Weight Gain in Animal Model of Aging
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Background
Investigating trajectories of aging using high-dimensional phenotyping in mice
MacArthur, M. R., & Mitchell, S. J. (2023) · Lab Animal · doi:10.1038/s41684-023-01122-3 · Cited by 1
Translationally controlled tumor protein restores impaired memory and altered synaptic protein expression in animal models of dementia
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Sex-specific resilience of neocortex to food restriction
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Study in Murine Model: Is There a Relationship Between Presbycusis and Frailty?
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Calorie restriction increases the sensitivity of progeroid Ercc1Δ/− mice to acute (neuro)inflammation
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Aging
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Background

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)
ORCID: Mitchell, Sarah J.
Fang, Evandro
Aon, Miguel
González-Reyes, José A.
Cortassa, Sonia
Kaushik, Susmita
Wahl, Devin
Burón, María I.
Palacios, Hector H.
Cai, Huan
Hine, Christopher
Broeskamp, Filomena
Dawson, John
Beasley, T. Mark
Wan, Junxiang
Ikeno, Yuji
Becker, Kevin G.
Zhang, Yongqing
Bohr, Vilhelm A.
Ferrucci, Luigi
Sinclair, David A.
Cohen, Pinchas
Egan, Josephine M.
Mitchell, James R.
Baur, Joseph A.
Allison, David B.
Anson, R. Michael
Villalba, José M.
Madeo, Frank
Pearson, Kevin J.
Ingram, Donald K.
Bernier, Michel
Venue: Cell Metabolism
Publisher: Elsevier BV
Published: 2016-06
Volume: 23
Issue: 6
Pages: 1093-1112
ISSN: 1550-4131 (ISSN-L)
DOI: 10.1016/j.cmet.2016.05.027
PMC: PMC4911707
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: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 378 d)
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 (medical) › 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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Effects of Sex, Strain, and Energy Intake on Hallmarks of Aging in Mice

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