SUN-LB009 Epigenetic Changes in Response to Metabolic Modifiers in Late Life: Exercise, High Fat Diet, and Angiotenin1-7 Effects on Metabolic Health and DNA Methylation in Frail Old Mice

Background: Reduced muscle and bone-mass and quality as well as impaired energy homeostasis are seen in both aging and the metabolic syndrome (MetS). We previously showed that exercise and Angiotensin1-7 (A1-7) ameliorate this burden in young rats, but their effect vis-a-vis aging is unknown. Aims: To assess the effects of exercise under normal and high-fat diet (HFD) with or without A1-7 on bone architecture and muscle quality as well as on musculoskeletal and fat epigenetic signatures in aged mice. Methods: 19-months-old-mice receiving HFD or normal-chow (NC) with or without 3-months exercise (treadmill, 6 days/week, 20 min/day or A1-7 (0.6 mcg/kg/d). Bone was evaluated by microCT. Global quantification of the epigenetic modification 5-methyl-or hydroxyl-methyl cytosine (5mC; 5hmc) by LC-MS/MS in white/brown adipose tissue (WAT; BAT) and Gastrocnemius muscle. Results: Old, sedentary mice were metabolically "starved" with low serum glucose and triglycerides. (A) Neither exercise nor high fat diet elicited sustained changes in body weight in old mice. B) Exercise per se rehabilitated glucose, triglycerides levels and muscle quality (enhanced muscle-fiber sectional area), accompanied by reduction in muscle 5mC and in BAT 5hmc (p\lt;0.05). (C) Combination of exercise with A1-7 improved bone geometry and density in NC mice but not during HFD. Combination of A1-7 and exercise led to a reduction in global 5mC levels both in the gastrocnemius muscle and in WAT (p\lt;0.05), thus suggesting that some of the effects maybe induced by changes in methylation patterns. Conclusions: The beneficial effects of A1-7 and exercise in aging skeletal tissue are operative only in NC but not in the presence of HFD. These beneficial effects are accompanied, and indeed, may be partly mediated by reversal of gene silencing as depicted by lesser DNA methylation in skeletal muscle. Finally, this is the first report that exercise can induce epigenetic changes in BAT, independent of changes in body weight. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.