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Cell Metab. 2016 Jun 14;23(6):1093-1112. doi: 10.1016/j.cmet.2016.05.027.

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

Author information

1
Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, NIH, 251 Bayview Boulevard, Suite 100, Baltimore, MD 21224, USA.
2
Department of Developmental and Molecular Biology, Institute for Aging Studies, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
3
Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, NIH, 251 Bayview Boulevard, Suite 100, Baltimore, MD 21224, USA; Laboratory of Molecular Gerontology, Intramural Research Program, National Institute on Aging, NIH, 251 Bayview Boulevard, Suite 100, Baltimore, MD 21224, USA; Department of Cellular and Molecular Medicine, Center for Healthy Aging, University of Copenhagen, 2200 Copenhagen, Denmark.
4
Laboratory of Molecular Gerontology, Intramural Research Program, National Institute on Aging, NIH, 251 Bayview Boulevard, Suite 100, Baltimore, MD 21224, USA.
5
Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, NIH, 251 Bayview Boulevard, Suite 100, Baltimore, MD 21224, USA.
6
Department of Cell Biology, Physiology and Immunology, University of Córdoba, Agrifood Campus of International Excellence, ceiA3, 14071 Córdoba, Spain.
7
Laboratory of Clinical Investigation, Intramural Research Program, National Institute on Aging, NIH, 251 Bayview Boulevard, Suite 100, Baltimore, MD 21224, USA.
8
Department of Physiology, Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Philadelphia, PA 19104, USA.
9
Department of Genetics and Complex Diseases, Harvard University, Boston, MA 02115, USA.
10
Institute of Molecular Biosciences, NAWI Graz, University of Graz, and BioTechMed Graz, 8010 Graz, Austria.
11
Department of Biostatistics, University of Alabama, Birmingham, AL 35294, USA; GRECC, Birmingham/Atlanta Veterans Administration Hospital, Birmingham, AL 35294, USA.
12
Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA.
13
Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX 78245-3207, USA.
14
Laboratory of Genetics, Intramural Research Program, National Institute on Aging, NIH, 251 Bayview Boulevard, Suite 100, Baltimore, MD 21224, USA.
15
Centro Andaluz de Biologia del Desarrollo, and CIBERER, Instituto de Salud Carlos III, Universidad Pablo de Olavide-CSIC, 41013 Sevilla, Spain.
16
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
17
Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, NIH, 251 Bayview Boulevard, Suite 100, Baltimore, MD 21224, USA; Graduate Center for Nutritional Sciences, University of Kentucky, C.T. Wethington Building, Room 591, 900 South Limestone, Lexington, KY 40536, USA.
18
Pennington Biomedical Research Center, Baton Rouge, LA 70809, USA.
19
Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, NIH, 251 Bayview Boulevard, Suite 100, Baltimore, MD 21224, USA. Electronic address: decabora@mail.nih.gov.

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.

PMID:
27304509
PMCID:
PMC4911707
DOI:
10.1016/j.cmet.2016.05.027
[Indexed for MEDLINE]
Free PMC Article

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