PMID- 21631380 OWN - NLM STAT- MEDLINE DCOM- 20111207 LR - 20211020 IS - 1557-8577 (Electronic) IS - 1549-1684 (Print) IS - 1549-1684 (Linking) VI - 14 IP - 3 DP - 2011 Jun TI - An exploratory analysis of the effects of a weight loss plus exercise program on cellular quality control mechanisms in older overweight women. PG - 315-24 LID - 10.1089/rej.2010.1132 [doi] AB - Obese older adults are particularly susceptible to sarcopenia and have a higher prevalence of disability than their peers of normal weight. Interventions to improve body composition in late life are crucial to maintaining independence. The main mechanisms underlying sarcopenia have not been determined conclusively, but chronic inflammation, apoptosis, and impaired mitochondrial function are believed to play important roles. It has yet to be determined whether impaired cellular quality control mechanisms contribute to this process. The objective of this study was to assess the effects of a 6-month weight loss program combined with moderate-intensity exercise on the cellular quality control mechanisms autophagy and ubiquitin-proteasome, as well as on inflammation, apoptosis, and mitochondrial function, in the skeletal muscle of older obese women. The intervention resulted in significant weight loss (8.0 +/- 3.9 % vs. 0.4 +/- 3.1% of baseline weight, p = 0.002) and improvements in walking speed (reduced time to walk 400 meters, - 20.4 +/- 16% vs. - 2.5 +/- 12%, p = 0.03). In the intervention group, we observed a three-fold increase in messenger RNA (mRNA) levels of the autophagy regulators LC3B, Atg7, and lysosome-associated membrane protein-2 (LAMP-2) compared to controls. Changes in mRNA levels of FoxO3A and its targets MuRF1, MAFBx, and BNIP3 were on average seven-fold higher in the intervention group compared to controls, but these differences were not statistically significant. Tumor necrosis factor-alpha (TNF-alpha) mRNA levels were elevated after the intervention, but we did not detect significant changes in the downstream apoptosis markers caspase 8 and 3. Mitochondrial biogenesis markers (PGC1alpha and TFAm) were increased by the intervention, but this was not accompanied by significant changes in mitochondrial complex content and activity. In conclusion, although exploratory in nature, this study is among the first to report the stimulation of cellular quality control mechanisms elicited by a weight loss and exercise program in older obese women. FAU - Wohlgemuth, Stephanie E AU - Wohlgemuth SE AD - Department of Aging and Geriatrics, Institute on Aging, College of Medicine, University of Florida, Gainesville, FL 32611-0910, USA. steffiw@ufl.edu FAU - Lees, Hazel A AU - Lees HA FAU - Marzetti, Emanuele AU - Marzetti E FAU - Manini, Todd M AU - Manini TM FAU - Aranda, Juan M AU - Aranda JM FAU - Daniels, Michael J AU - Daniels MJ FAU - Pahor, Marco AU - Pahor M FAU - Perri, Michael G AU - Perri MG FAU - Leeuwenburgh, Christian AU - Leeuwenburgh C FAU - Anton, Stephen D AU - Anton SD LA - eng GR - K23 AT004251/AT/NCCIH NIH HHS/United States GR - P30 AG028740/AG/NIA NIH HHS/United States GR - P30AG028740/AG/NIA NIH HHS/United States GR - K23 AT004251-01A2/AT/NCCIH NIH HHS/United States PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20110601 PL - United States TA - Rejuvenation Res JT - Rejuvenation research JID - 101213381 SB - IM MH - Aged MH - Apoptosis/genetics MH - *Autophagy/genetics MH - *Exercise MH - Female MH - Gene Expression Regulation MH - Humans MH - Inflammation/complications/genetics MH - Middle Aged MH - Mitochondria/metabolism MH - Overweight/complications/genetics/*pathology/*therapy MH - *Weight Loss/genetics PMC - PMC3136739 EDAT- 2011/06/03 06:00 MHDA- 2011/12/13 00:00 PMCR- 2012/06/01 CRDT- 2011/06/03 06:00 PHST- 2011/06/03 06:00 [entrez] PHST- 2011/06/03 06:00 [pubmed] PHST- 2011/12/13 00:00 [medline] PHST- 2012/06/01 00:00 [pmc-release] AID - 10.1089/rej.2010.1132 [pii] AID - 10.1089/rej.2010.1132 [doi] PST - ppublish SO - Rejuvenation Res. 2011 Jun;14(3):315-24. doi: 10.1089/rej.2010.1132. Epub 2011 Jun 1.