Abstract This article focuses on the current underlying of molecular mechanisms of the peroxisome proliferator-activated receptor-g coactivator-1α (PGC-1α) mediated pathway and discuss possible therapeutic benefits of increased mitochondrial biogenesis in compensating for mitochondrial dysfunction and ameliorating aging and aging-related diseases. PGC-1α is the master transcription regulator that stimulates mitochondrial biogenesis, by upregulating nuclear respiratory factors and mitochondrial transcription factor A, leading to increased mitochondrial DNA replication and gene transcription. PGC-1a also regulates cellular oxidant-antioxidant homeostasis by stimulating the gene expression of superoxide dismutase-2, catalase, glutathione peroxidase 1, and uncoupling protein. Recent reports from muscle-specific PGC-1α overexpression underline the benefit of PGC-1α in muscle atrophy and sarcopenia, during which PGC-1α enhanced mitochondrial biogenic pathway and reduced oxidative damage. Thus, PGC-1α seems to have a protective role against aging associated skeletal muscle deterioration.
Significant point: PGC-1α has been identified as a master regulator of a wide range of cellular functions and gene expression. This review summaries its critical role in skeletal muscle in terms of energy metabolism, antioxidant homeostasis, and inflammation, ultimately affecting muscle health and aging.
Corresponding Authors: Laboratory of Physiological Hygiene and Exercise Science, School of Kinesiology, University of Minnesota, Minneapolis, MN 55455, USA
Cite this article:
Chounghun Kang, Li Li Ji. Role of PGC-1α in muscle function and aging[J]. Journal of Sport and Health Science, 2013, 2(2): 81-86.
Kang C,Ji LL.Role of PGC-1a signaling in skeletal muscle health anddisease.Ann N Y Acad Sci 2012;1271:110-7.
Phillips SK,Bruce SA,Newton D,Woledge RC.The weakness of oldage is not due to failure of muscle activation.J Gerontol 1992;47:45-9.
Mattson MP,Maudsley S,Martin B.A neural signaling triumvirate thatinfluences ageing and age-related disease:insulin/IGF-1,BDNF and se-rotonin.Ageing Res Rev 2004;3:445-64.
Wen CP,Wai JP,Tsai MK,Yang YC,Cheng TY,Lee MC,et al.Minimumamount of physical activity for reduced mortality and extended lifeexpectancy: a prospective cohort study.Lancet 2011;378:1244-53.
Iversen N,Krustrup P,Rasmussen HN,Rasmussen UF,Saltin B,Pilegaard H.Mitochondrial biogenesis and angiogenesis in skeletalmuscle of the elderly.Exp Gerontol 2011;46:670-8.
Hasson CJ,Miller RH,Caldwell GE.Contractile and elastic ankle jointmuscular properties in young and older adults.PLoS One 2011;6:15953.
Zou J,Crews F.CREB and NF-KappaB transcription factors regulatesensitivity to excitotoxic and oxidative stress induced neuronal cell death.Cell Mol Neurobiol 2006;26:385-405.
Vaynman S,Ying Z,Gomez-Pinilla F.Interplay between brain-derivedneurotrophic factor and signal transduction modulators in the regulation oftheeffectsofexerciseonsynaptic-plasticity.Neuroscience2003;122:647-57.
Vaynman S,Ying Z,Gomez-Pinilla F.Hippocampal BDNF mediates theefficacy of exercise on synaptic plasticity and cognition.Eur J Neurosci2004;20:2580-90.
Bortz WM 2nd.Disuse and aging.JAMA 1982;248:1203-8.
Herbst A,Pak JW,McKenzie D,Bua E,Bassiouni M,Aiken JM.Accu-mulation of mitochondrial DNA deletion mutations in aged muscle fibers:evidence for a causal role in muscle fiber loss.J Gerontol A Biol Sci MedSci 2007;62:235-45.
Drew B,Phaneuf S,Dirks A,Selman C,Gredilla R,Lezza A,et al.Effectsof aging and caloric restriction on mitochondrial energy production ingastrocnemius muscle and heart.Am J Physiol Regul Integr Comp Physiol2003;284:R474-80.
Ochala J,Dorer DJ,Frontera WR,Krivickas LS.Single skeletal musclefiber behavior after a quick stretch in young and older men:a possibleexplanation of the relative preservation of eccentric force in old age.Pflugers Arch 2006;452:464-70.
Wang H,Yuan G,Prabhakar NR,Boswell M,Katz DM.Secretion of brain-derived neurotrophic factor from PC12 cells in response to oxidative stressrequires autocrine dopamine signaling.J Neurochem 2006;96:694-705.
Bua EA,McKiernan SH,Wanagat J,McKenzie D,Aiken JM.Mito-chondrial abnormalities are more frequent in muscles undergoing sarco-penia.J Appl Physiol 2002;92:2617-24.
Byberg L,Melhus H,Gedeborg R,Sundstro öm J,Ahlbom A,Zethelius B,et al.Total mortality after changes in leisure time physical activity in 50year old men: 35 year follow-up of population based cohort.Br J SportsMed 2009;43:482.
Faulkner JA,Brooks SV,Zerba E.Muscle atrophy and weakness withaging:contraction-induced injury as an underlying mechanism.J Ger-ontol A Biol Sci Med Sci 1995;50:124-9.
0.Rader EP,Faulkner JA.Effect of aging on the recovery following con-traction-induced injury in muscles of female mice.J Appl Physiol2006;101:887-92.
1.Rader EP,Faulkner JA.Recovery from contraction-induced injury isimpaired in weight-bearing muscles of old male mice.J Appl Physiol2006;100:656-61.
2.Buford TW,Macneil RG,Clough LG,Dirain M,Sandesara B,Pahor M,et al.Active muscle regeneration following eccentric contraction-induced injury is similar between healthy young and older adults.J Appl Physiol 2013.http://dx.doi.org/10.1152/japplphysiol.01350.2012 [Epubahead of print].
Wang Y,Tuomilehto J,Jousilahti P,Antikainen R,Ma öho önen M,Katzmarzyk PT,et al.Occupational,commuting,and leisure-time physicalactivity in relation to heart failure among finnish men and women.J AmColl Cardiol 2010;56:1140-8.
Mansouri A,Muller FL,Liu Y,Ng R,Faulkner J,Hamilton M,et al.Alterations in mitochondrial function,hydrogen peroxide release andoxidative damage in mouse hind-limb skeletal muscle during aging.MechAgeing Dev 2006;127:298-306.
Nusselder WJ,Franco OH,Peeters A,Mackenbach JP.Living healthier forlonger: comparative effects of three heart-healthy behaviors on lifeexpectancy with and without cardiovascular disease.BMC Public Health2009;9:487.
Edwards RH,Hill DK,Jones DA,Merton PA.Fatigue of long duration inhuman skeletal muscle after exercise.J Physiol 1977;272:769-78.
Toldy A,Stadler K,Sasvari M,Jakus J,Jung KJ,Chung HY,et al.Theeffect of exercise and nettle supplementation on oxidative stress markersin the rat brain.Brain Res Bull 2005;65:487-93.
Siamilis S,Jakus J,Nyakas C,Costa A,Mihalik B,Falus A,et al.Theeffect of exercise and oxidant-antioxidant intervention on the levels ofneurotrophins and free radicals in spinal cord of rats.Spinal Cord2009;47:453-7.
Jonker JT,De Laet C,Franco OH,Peeters A,Mackenbach J,Nusselder WJ.Physical activity and life expectancy with and without diabetes: life tableanalysis of the framingham heart study.Diabetes Care 2006;29:38-43.
Melov S,Tarnopolsky MA,Beckman K,Felkey K,Hubbard A.Resistanceexercise reverses aging in human skeletal muscle.PLoS One 2007;2:e465.
Terman A,Gustafsson B,Brunk UT.Mitochondrial damage and intra-lysosomaldegradationincellular aging.MolAspectsMed2006;27:471-82.
Suwa M,Nakano H,Radak Z,Kumagai S.Endurance exercise increasesthe SIRT1 and peroxisome proliferator-activated receptor gamma coac-tivator-1alpha protein expressions in rat skeletal muscle.Metabolism2008;57:986-98.
Matiello R,Fukui RT,Silva ME,Rocha DM,Wajchenberg BL,Azhar S,et al.Differential regulation of PGC-1alpha expression in rat liver andskeletal muscle in response to voluntary running.Nutr Metab (Lond)2010;7:36.
Ingalls CP,Warren GL,Williams JH,Ward CW,Armstrong RB.E-Ccoupling failure in mouse EDL muscle after in vivo eccentric contrac-tions.J Appl Physiol 1998;85:58-67.
Park C,Shin KS,Ryu JH,Kang K,Kim J,Ahn H,et al.The inhibition ofnitric oxide synthase enhances PSA-NCAM expression and creb phos-phorylation in the rat hippocampus.Neuroreport 2004;15:231-4.