title: Late-onset caloric restriction alters skeletal muscle metabolism by modulating pyruvate metabolism.
abstract: Caloric restriction (CR) attenuates age-related muscle loss. However, the underlying mechanism responsible for this attenuation is not fully understood. This study evaluated the role of energy metabolism in the CR-induced attenuation of muscle loss. The aims of this study were twofold: 1) to evaluate the effect of CR on energy metabolism and determine its relationship with muscle mass, and 2) to determine whether the effects of CR are age dependent. Young and middle-aged rats were randomized into either 40% CR or ad libitum (AL) diet groups for 14 wk. Major energy-producing pathways in muscles, i.e., glycolysis and mitochondrial oxidative phosphorylation (OXPHOS), were examined. We found that the effects of CR were age dependent. CR improved muscle metabolism and normalized muscle mass in middle-aged animals but not young animals. CR decreased glycolysis and increased the cellular dependency for OXPHOS vs. glycolysis in muscles of middle-aged rats, which was associated with the improvement of normalized muscle mass. The metabolic reprogramming induced by CR was related to modulation of pyruvate metabolism and increased mitochondrial biogenesis. Compared with animals fed AL, middle-aged animals with CR had lower lactate dehydrogenase A content and greater mitochondrial pyruvate carrier content. Markers of mitochondrial biogenesis, including AMPK activation levels and SIRT1 and COX-IV content, also showed increased levels. In conclusion, 14 wk of CR improved muscle metabolism and preserved muscle mass in middle-aged animals but not in young developing animals. CR-attenuated age-related muscle loss is associated with reprogramming of the metabolic pathway from glycolysis to OXPHOS.
authors.affiliation: Department of Physical Therapy, Medical School, Chang Gung University, Tao-Yuan, Taiwan; Healthy Aging Research Center, Chang Gung University, Tao-Yuan, Taiwan; cnchen@mail.cgu.edu.tw.
authors.forename: Chiao-Nan Joyce
authors.initials: CN
authors.lastname: Chen
authors.affiliation: Department of Physical Therapy, Medical School, Chang Gung University, Tao-Yuan, Taiwan;
authors.forename: Shang-Ying
authors.initials: SY
authors.lastname: Lin
authors.affiliation: Department of Exercise and Health Science, College of Human Development and Health, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan; and.
authors.forename: Yi-Hung
authors.initials: YH
authors.lastname: Liao
authors.affiliation: Department of Physical Therapy, Medical School, Chang Gung University, Tao-Yuan, Taiwan;
authors.forename: Zhen-Jie
authors.initials: ZJ
authors.lastname: Li
authors.affiliation: Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, Taipei, Taiwan.
authors.forename: Alice May-Kuen
authors.initials: AM
authors.lastname: Wong
mesh_terms: D000367:Age Factors; D000375:Aging / Q000378:metabolism*; D000818:Animals; D031204:Caloric Restriction; D004734:Energy Metabolism; D007527:Isoenzymes / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D000080864:Lactate Dehydrogenase 5; D008931:Mitochondria, Muscle / Q000378:metabolism; D018482:Muscle, Skeletal / Q000033:anatomy & histology / Q000378:metabolism*; D009929:Organ Size; D019289:Pyruvic Acid / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D007527:Isoenzymes; D019289:Pyruvic Acid; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5
keywords: dietary restriction; glycolysis; lactate dehydrogenase; mitochondrial pyruvate carrier; muscle