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Calorie restriction reduces biomarkers of cellular senescence in humans |
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| Authors: | Zaira Aversa Thomas A White Amanda A Heeren Cassondra A Hulshizer Dominik Saul Xu Zhang Anthony J A Molina Leanne M Redman Corby K Martin Susan B Racette Kim M Huffman Manjushri Bhapkar Sundeep Khosla Sai Krupa Das Roger A Fielding Elizabeth J Atkinson Nathan K LeBrasseur |
| Institution: | 1. Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, Minnesota, USA
Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, Minnesota, USA;2. Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, Minnesota, USA;3. Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota, USA;4. Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, Minnesota, USA Department of Trauma and Reconstructive Surgery, Eberhard Karls University Tübingen, BG Trauma Center Tübingen, Tübingen, Germany;5. Department of Medicine, University of California San Diego, La Jolla, California, USA;6. Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA;7. College of Health Solutions, Arizona State University, Phoenix, Arizona, USA Program in Physical Therapy, Washington University School of Medicine, St. Louis, Missouri, USA;8. Duke Clinical Research Institute and Molecular Physiology Institute, School of Medicine, Durham, North Carolina, USA;9. Energy Metabolism Team, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts, USA;10. Nutrition, Exercise Physiology and Sarcopenia Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts, USA |
| Abstract: | Calorie restriction (CR) with adequate nutrient intake is a potential geroprotective intervention. To advance this concept in humans, we tested the hypothesis that moderate CR in healthy young-to-middle-aged individuals would reduce circulating biomarkers of cellular senescence, a fundamental mechanism of aging and aging-related conditions. Using plasma specimens from the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE™) phase 2 study, we found that CR significantly reduced the concentrations of several senescence biomarkers at 12 and 24 months compared to an ad libitum diet. Using machine learning, changes in biomarker concentrations emerged as important predictors of the change in HOMA-IR and insulin sensitivity index at 12 and 24 months, and the change in resting metabolic rate residual at 12 months. Finally, using adipose tissue RNA-sequencing data from a subset of participants, we observed a significant reduction in a senescence-focused gene set in response to CR at both 12 and 24 months compared to baseline. Our results advance the understanding of the effects of CR in humans and further support a link between cellular senescence and metabolic health. |
| Keywords: | aging biomarkers CALERIE™ caloric restriction inflammation metabolism senescence-associated secretory phenotype |