1. Effects of sex, strain, and energy intake on hallmarks of aging in mice
- Author
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Ministerio de Economía y Competitividad (España), Consejo Superior de Investigaciones Científicas (España), National Institutes of Health (US), American Diabetes Association, Research Foundation - Flanders, Federal Ministry of Education and Research (Germany), Universidad de Córdoba (España), Mitchell, Sarah J., González-Reyes, José A., Calvo-Rubio, Miguel, Ikeno, Yuji, Becker, Kevin G., Zhang, Yongqing, Longo, Dan L., Navas, Plácido, Sinclair, David A., Egan, Josephine M., Baur, Joseph A., Villalba, José M., Pearson, Kevin J., Ingram, Donald K., Cabo, Rafael de, Ministerio de Economía y Competitividad (España), Consejo Superior de Investigaciones Científicas (España), National Institutes of Health (US), American Diabetes Association, Research Foundation - Flanders, Federal Ministry of Education and Research (Germany), Universidad de Córdoba (España), Mitchell, Sarah J., González-Reyes, José A., Calvo-Rubio, Miguel, Ikeno, Yuji, Becker, Kevin G., Zhang, Yongqing, Longo, Dan L., Navas, Plácido, Sinclair, David A., Egan, Josephine M., Baur, Joseph A., Villalba, José M., Pearson, Kevin J., Ingram, Donald K., and Cabo, Rafael de
- 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.
- Published
- 2016