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Overweight in the Elderly Induces a Switch in Energy Metabolism that Undermines Muscle Integrity
Yaiza Potes1,2, Zulema Perez-Martinez3, Juan C. Bermejo-Millo Juan1,2, Adrian Rubio-Gonzalez1, Maria Fernandez-Fernandez4, Manuel Bermudez4, Jose M. Arche4, Juan J. Solano 2,4, Jose A. Boga3, Mamen Olivan2,5, Beatriz Caballero1,2, Ignacio Vega-Naredo1,2, Ana Coto-Montes1,2,*
1Department of Morphology and Cell Biology, Faculty of Medicine, University of Oviedo, Asturias, Spain
2Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Spain
3Microbiology Service, Central University Hospital of Asturias, Asturias, Spain
4Geriatric Service, Monte Naranco Hospital, Asturias, Spain
5Servicio Regional de Investigación y Desarrollo Agroalimentario (SERIDA), Asturias, Spain
5Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Spain
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Abstract  

Aging is characterized by a progressive loss of skeletal muscle mass and function (sarcopenia). Obesity exacerbates age-related decline and lead to frailty. Skeletal muscle fat infiltration increases with aging and seems to be crucial for the progression of sarcopenia. Additionally, skeletal muscle plasticity modulates metabolic adaptation to different pathophysiological situations. Thus, cellular bioenergetics and mitochondrial profile were studied in the skeletal muscle of overweight aged people without reaching obesity to prevent this extreme situation. Overweight aged muscle lacked ATP production, as indicated by defects in the phosphagen system, glycolysis and especially mostly by oxidative phosphorylation metabolic pathway. Overweight subjects exhibited an inhibition of mitophagy that was linked to an increase in mitochondrial biogenesis that underlies the accumulation of dysfunctional mitochondria and encourages the onset of sarcopenia. As a strategy to maintain cellular homeostasis, overweight subjects experienced a metabolic switch from oxidative to lactic acid fermentation metabolism, which allows continued ATP production under mitochondrial dysfunction, but without reaching physiological aged basal levels. This ATP depletion induced early signs of impaired contractile function and a decline in skeletal muscle structural integrity, evidenced by lower levels of filamin C. Our findings reveal the main effector pathways at an early stage of obesity and highlight the importance of mitochondrial metabolism in overweight and obese individuals. Exploiting mitochondrial profiles for therapeutic purposes in humans is an ambitious strategy for treating muscle impairment diseases.

Keywords overweight      elderly      glycolysis      mitochondrial metabolism      aged-related atrophy     
Corresponding Authors: Coto-Montes Ana   
Issue Date: 29 March 2018
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Yaiza Potes
Zulema Perez-Martinez
Juan C. Bermejo-Millo Juan
Adrian Rubio-Gonzalez
Maria Fernandez-Fernandez
Manuel Bermudez
et al.
Cite this article:   
Yaiza Potes,Zulema Perez-Martinez,Juan C. Bermejo-Millo Juan, et al. Overweight in the Elderly Induces a Switch in Energy Metabolism that Undermines Muscle Integrity[J]. A&D, 10.14336/AD.2018.0430
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http://www.aginganddisease.org/EN/10.14336/AD.2018.0430     OR     http://www.aginganddisease.org/EN/Y0/V/I/0
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