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

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

Research output: Contribution to journalArticle

138 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1093-1112
Number of pages20
JournalCell metabolism
Volume23
Issue number6
DOIs
StatePublished - Jun 14 2016

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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    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., ... De Cabo, R. (2016). Effects of Sex, Strain, and Energy Intake on Hallmarks of Aging in Mice. Cell metabolism, 23(6), 1093-1112. https://doi.org/10.1016/j.cmet.2016.05.027