Impact of Aging and Exercise on Mitochondrial Quality Control in Skeletal Muscle

Oxidative Medicine and Cellular Longevity

Volumn 2017, Issue , 2017, Pages

  Kim, Yuho ^a,b   Triolo, Matthew ^a,b   Hood, David A ^a,b  

^a YORK UNIVERSITY   (Canada)

^b YORK UNIVERSITY   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

BIOSYNTHESIS; MITOCHONDRIA; MUSCLE;

DYNAMIC CONTROLS; ENERGY PRODUCTIONS; MITOCHONDRIAL BIOGENESIS; PROTEIN IMPORT; REACTIVE OXYGEN SPECIES; RESISTANCE EXERCISE; SKELETAL MUSCLE; TRANSCRIPTIONAL REGULATION;

QUALITY CONTROL;

HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; MITOCHONDRIAL DNA; MITOCHONDRIAL TRANSCRIPTION FACTOR A; NICOTINAMIDE ADENINE DINUCLEOTIDE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA COACTIVATOR 1ALPHA; PROTEIN P53; TRANSCRIPTION FACTOR;

AGING; AUTOPHAGY; ENDURANCE TRAINING; EXERCISE; HUMAN; MITOCHONDRIAL BIOGENESIS; MITOCHONDRIAL DYNAMICS; MITOCHONDRION; MITOPHAGY; NONHUMAN; RESISTANCE TRAINING; REVIEW; SKELETAL MUSCLE; AGED; METABOLISM; PHYSIOLOGY; QUALITY CONTROL; VERY ELDERLY;

AGING; CELLS; NUCLEIC ACIDS; QUALITY CONTROL;

AGED; AGED, 80 AND OVER; AGING; EXERCISE; HUMANS; MITOCHONDRIA; MUSCLE, SKELETAL; QUALITY CONTROL; TRANSCRIPTION FACTORS;

EID: 85021633496     PISSN: 19420900     EISSN: 19420994     Source Type: Journal    
DOI: 10.1155/2017/3165396     Document Type: Review

References (194)

1. I. H. Rosenberg, "Sarcopenia: origins and clinical relevance, " The Journal of Nutrition, vol. 127, no. 5, Supplement, pp. 990S-991S, 1997.
2. D. Heber, S. Ingles, J. M. Ashley, M. H. Maxwell, R. F. Lyons, and R. M. Elashoff, "Clinical detection of sarcopenic obesity by bioelectrical impedance analysis, " The American Journal of Clinical Nutrition, vol. 64, no. 3, Supplement, pp. 472S-477S, 1996.
3. A. Hiona, A. Sanz, G. C. Kujoth et al., "Mitochondrial DNA mutations induce mitochondrial dysfunction, apoptosis and sarcopenia in skeletal muscle of mitochondrial DNA mutator mice, " PloS One, vol. 5, no. 7, article e11468, 2010.
4. G. C. Kujoth, A. Hiona, T. D. Pugh et al., "Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging, " Science, vol. 309, no. 5733, pp. 481-484, 2005.
5. L. A. Schaap, S. M. Pluijm, D. J. Deeg, and M. Visser, "Inflammatory markers and loss of muscle mass (sarcopenia) and strength, " The American Journal of Medicine, vol. 119, no. 6, p. 526, 2006.
6. L. A. Esposito, S. Melov, A. Panov, B. A. Cottrell, and D. C. Wallace, "Mitochondrial disease in mouse results in increased oxidative stress, " Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 9, pp. 4820-4825, 1999.
7. E. Rapizzi, P. Pinton, G. Szabadkai et al., "Recombinant expression of the voltage-dependent anion channel enhances the transfer of Ca2+ microdomains to mitochondria, " The Journal of Cell Biology, vol. 159, no. 4, pp. 613-624, 2002.
8. S. Iqbal, O. Ostojic, K. Singh, A. M. Joseph, and D. A. Hood, "Expression of mitochondrial fission and fusion regulatory proteins in skeletal muscle during chronic use and disuse, " Muscle & Nerve, vol. 48, no. 6, pp. 963-970, 2013.
9. J. P. Leduc-Gaudet, M. Picard, F. St-Jean Pelletier et al., "Mitochondrial morphology is altered in atrophied skeletal muscle of aged mice, " Oncotarget, vol. 6, no. 20, pp. 17923-17937, 2015.
10. M. Navratil, A. Terman, and E. A. Arriaga, "Giant mitochondria do not fuse and exchange their contents with normal mitochondria, " Experimental Cell Research, vol. 314, no. 1, pp. 164-172, 2008.
11. J. M. Zahn, R. Sonu, H. Vogel et al., "Transcriptional profiling of aging in human muscle reveals a common aging signature, " PLoS Genetics, vol. 2, no. 7, article e115, 2006.
12. E. Bua, J. Johnson, A. Herbst et al., "Mitochondrial DNAdeletion mutations accumulate intracellularly to detrimental levels in aged human skeletal muscle fibers, " American Journal of Human Genetics, vol. 79, no. 3, pp. 469-480, 2006.
13. C. N. Lyons, O. Mathieu-Costello, and C. D. Moyes, "Regulation of skeletal muscle mitochondrial content during aging, " The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, vol. 61, no. 1, pp. 3-13, 2006.
14. V. Ljubicic and D. A. Hood, "Diminished contractioninduced intracellular signaling towards mitochondrial biogenesis in aged skeletal muscle, " Aging Cell, vol. 8, no. 4, pp. 394-404, 2009.
15. V. Ljubicic, A. M. Joseph, P. J. Adhihetty et al., "Molecular basis for an attenuated mitochondrial adaptive plasticity in aged skeletal muscle, " Aging (Albany, NY), vol. 1, no. 9, pp. 818-830, 2009.
16. S. E. Calvo, K. R. Clauser, and V. K. Mootha, "MitoCarta2. 0: An updated inventory of mammalian mitochondrial proteins, " Nucleic Acids Research, vol. 44, no. D1, pp. D1251-D1257, 2016.
17. J. W. Taanman, "The mitochondrial genome: structure, transcription, translation and replication, " Biochimica et Biophysica Acta, vol. 1410, no. 2, pp. 103-123, 1999.
18. K. Boengler, G. Heusch, and R. Schulz, "Nuclear-encoded mitochondrial proteins and their role in cardioprotection, " Biochimica et Biophysica Acta, vol. 1813, no. 7, pp. 1286-1294, 2011.
19. J. Lin, H. Wu, P. T. Tarr et al., "Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibres, " Nature, vol. 418, no. 6899, pp. 797-801, 2002.
20. P. Puigserver, Z. Wu, C. W. Park, R. Graves, M. Wright, and B. M. Spiegelman, "A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis, " Cell, vol. 92, no. 6, pp. 829-839, 1998.
21. O. H. Mortensen, L. Frandsen, P. Schjerling, E. Nishimura, and N. Grunnet, "PGC-1alpha and PGC-1beta have both similar and distinct effects on myofiber switching toward an oxidative phenotype, " American Journal of Physiology. Endocrinology and Metabolism, vol. 291, no. 4, pp. E807-E816, 2006.
22. V. K. Mootha, C. M. Lindgren, K. F. Eriksson et al., "PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes, " Nature Genetics, vol. 34, no. 3, pp. 267-273, 2003.
23. T. C. Leone, J. J. Lehman, B. N. Finck et al., "PGC-1alpha deficiency causes multi-system energy metabolic derangements: muscle dysfunction, abnormal weight control and hepatic steatosis, " PLoS Biology, vol. 3, no. 4, article e101, 2005.
24. C. Zechner, L. Lai, J. F. Zechner et al., "Total skeletal muscle PGC-1 deficiency uncouples mitochondrial derangements from fiber type determination and insulin sensitivity, " Cell Metabolism, vol. 12, no. 6, pp. 633-642, 2010.
25. L. W. Finley, J. Lee, and A. Souza, "Skeletal muscle transcriptional coactivator PGC-1alpha mediates mitochondrial, but not metabolic, changes during calorie restriction, " Proceedings of the National Academy of Sciences of the United States of America, vol. 109, no. 8, pp. 2931-2936, 2012.
26. R. B. Vega, J. M. Huss, and D. P. Kelly, "The coactivator PGC-1 cooperates with peroxisome proliferator-activated receptor alpha in transcriptional control of nuclear genes encoding mitochondrial fatty acid oxidation enzymes, " Molecular and Cellular Biology, vol. 20, no. 5, pp. 1868-1876, 2000.
27. S. N. Schreiber, D. Knutti, K. Brogli, T. Uhlmann, and A. Kralli, "The transcriptional coactivator PGC-1 regulates the expression and activity of the orphan nuclear receptor estrogen-related receptor alpha (ERRalpha), " The Journal of Biological Chemistry, vol. 278, no. 11, pp. 9013-9018, 2003.
28. S. N. Schreiber, R. Emter, M. B. Hock et al., "The estrogenrelated receptor alpha (ERRalpha) functions in PPARgamma coactivator 1alpha (PGC-1alpha)-induced mitochondrial biogenesis, " Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 17, pp. 6472-6477, 2004.
29. P. Puigserver, G. Adelmant, Z. Wu et al., "Activation of PPARgamma coactivator-1 through transcription factor docking, " Science, vol. 286, no. 5443, pp. 1368-1371, 1999.
30. J. V. Virbasius and R. C. Scarpulla, "Activation of the human mitochondrial transcription factor A gene by nuclear respiratory factors: A potential regulatory link between nuclear and mitochondrial gene expression in organelle biogenesis, " Proceedings of the National Academy of Sciences of the United States of America, vol. 91, no. 4, pp. 1309-1313, 1994.
31. C. Handschin, J. Rhee, J. Lin, P. T. Tarr, and B. M. Spiegelman, "An autoregulatory loop controls peroxisome proliferator-activated receptor gamma coactivator 1alpha expression in muscle, " Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 12, pp. 7111-7116, 2003.
32. R. Amat, A. Planavila, S. L. Chen, R. Iglesias, M. Giralt, and F. Villarroya, "SIRT1 controls the transcription of the peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) gene in skeletal muscle through the PGC-1alpha autoregulatory loop and interaction with MyoD, " The Journal of Biological Chemistry, vol. 284, no. 33, pp. 21872-21880, 2009.
33. D. P. Millay and E. N. Olson, "Making muscle or mitochondria by selective splicing of PGC-1alpha, " Cell Metabolism, vol. 17, no. 1, pp. 3-4, 2013.
34. Y. Zhang, P. Huypens, A. W. Adamson et al., "Alternative mRNA splicing produces a novel biologically active short isoform of PGC-1alpha, " The Journal of Biological Chemistry, vol. 284, no. 47, pp. 32813-32826, 2009.
35. J. L. Ruas, J. P. White, R. R. Rao et al., "A PGC-1alpha isoform induced by resistance training regulates skeletal muscle hypertrophy, " Cell, vol. 151, no. 6, pp. 1319-1331, 2012.
36. M. Silvennoinen, J. P. Ahtiainen, J. J. Hulmi et al., "PGC-1 isoforms and their target genes are expressed differently in human skeletal muscle following resistance and endurance exercise, " Physiological Reports, vol. 3, no. 10, 2015.
37. J. S. Chang, V. Fernand, Y. B. Zhang et al., "NT-PGC-1 alpha protein is sufficient to link beta(3)-adrenergic receptor activation to transcriptional and physiological components of adaptive thermogenesis, " Journal of Biological Chemistry, vol. 287, no. 12, pp. 9100-9111, 2012.
38. X. Wen, J. Wu, J. S. Chang et al., "Effect of exercise intensity on isoform-specific expressions of NT-PGC-1 alpha mRNA in mouse skeletal muscle, " BioMed Research International, vol. 2014, Article ID 402175, 11 pages, 2014.
39. D. C. Wright, P. C. Geiger, D. H. Han, T. E. Jones, and J. O. Holloszy, "Calcium induces increases in peroxisome proliferator-activated receptor gamma coactivator-1alpha and mitochondrial biogenesis by a pathway leading to p38 mitogen-activated protein kinase activation, " The Journal of Biological Chemistry, vol. 282, no. 26, pp. 18793-18799, 2007.
40. D. Freyssenet, M. Di Carlo, and D. A. Hood, "Calciumdependent regulation of cytochrome c gene expression in skeletal muscle cells. Identification of a protein kinase cdependent pathway, " The Journal of Biological Chemistry, vol. 274, no. 14, pp. 9305-9311, 1999.
41. D. Freyssenet, I. Irrcher, M. K. Connor, M. Di Carlo, and D. A. Hood, "Calcium-regulated changes in mitochondrial phenotype in skeletal muscle cells, " American Journal of Physiology. Cell Physiology, vol. 286, no. 5, pp. C1053-C1061, 2004.
42. I. Irrcher, V. Ljubicic, and D. A. Hood, "Interactions between ROS and AMP kinase activity in the regulation of PGC-1alpha transcription in skeletal muscle cells, " American Journal of Physiology. Cell Physiology, vol. 296, no. 1, pp. C116-C123, 2009.
43. E. Nisoli, S. Falcone, C. Tonello et al., "Mitochondrial biogenesis by NO yields functionally active mitochondria in mammals, " Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 47, pp. 16507-16512, 2004.
44. I. Irrcher, P. J. Adhihetty, T. Sheehan, A. M. Joseph, and D. A. Hood, "PPARgamma coactivator-1alpha expression during thyroid hormone-and contractile activity-induced mitochondrial adaptations, " American Journal of Physiology. Cell Physiology, vol. 284, no. 6, pp. C1669-C1677, 2003.
45. Y. Zhang, K. Ma, S. Song, M. B. Elam, G. A. Cook, and E. A. Park, "Peroxisomal proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha) enhances the thyroid hormone induction of carnitine palmitoyltransferase I (CPT-I alpha), " The Journal of Biological Chemistry, vol. 279, no. 52, pp. 53963-53971, 2004.
46. Z. Gerhart-Hines, J. T. Rodgers, O. Bare et al., "Metabolic control of muscle mitochondrial function and fatty acid oxidation through SIRT1/PGC-1alpha, " The EMBO Journal, vol. 26, no. 7, pp. 1913-1923, 2007.
47. A. E. Civitarese, S. Carling, L. K. Heilbronn et al., "Calorie restriction increases muscle mitochondrial biogenesis in healthy humans, " PLoS Medicine, vol. 4, no. 3, article e76, 2007.
48. K. Baar, A. R. Wende, T. E. Jones et al., "Adaptations of skeletal muscle to exercise: rapid increase in the transcriptional coactivator PGC-1, " The FASEB Journal, vol. 16, no. 14, pp. 1879-1886, 2002.
49. B. Chabi, V. Ljubicic, K. J. Menzies, J. H. Huang, A. Saleem, and D. A. Hood, "Mitochondrial function and apoptotic susceptibility in aging skeletal muscle, " Aging Cell, vol. 7, no. 1, pp. 2-12, 2008.
50. C. Ling, P. Poulsen, E. Carlsson et al., "Multiple environmental and genetic factors influence skeletal muscle PGC-1alpha and PGC-1beta gene expression in twins, " The Journal of Clinical Investigation, vol. 114, no. 10, pp. 1518-1526, 2004.
51. A. R. Konopka, M. K. Suer, C. A. Wolff, and M. P. Harber, "Markers of human skeletal muscle mitochondrial biogenesis and quality control: effects of age and aerobic exercise training, " The Journals of Gerontology. Series a, Biological Sciences and Medical Sciences, vol. 69, no. 4, pp. 371-378, 2014.
52. S. Sczelecki, A. Besse-Patin, A. Abboud et al., "Loss of Pgc-1alpha expression in aging mouse muscle potentiates glucose intolerance and systemic inflammation, " American Journal of Physiology. Endocrinology and Metabolism, vol. 306, no. 2, pp. E157-E167, 2014.
53. M. Sandri, J. Lin, C. Handschin et al., "PGC-1alpha protects skeletal muscle from atrophy by suppressing FoxO3 action and atrophy-specific gene transcription, " Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 44, pp. 16260-16265, 2006.
54. J. J. Brault, J. G. Jespersen, and A. L. Goldberg, "Peroxisome proliferator-activated receptor gamma coactivator 1alpha or 1beta overexpression inhibits muscle protein degradation, induction of ubiquitin ligases, and disuse atrophy, " The Journal of Biological Chemistry, vol. 285, no. 25, pp. 19460-19471, 2010.
55. C. Canto, L. Q. Jiang, A. S. Deshmukh et al., "Interdependence of AMPK and SIRT1 for metabolic adaptation to fasting and exercise in skeletal muscle, " Cell Metabolism, vol. 11, no. 3, pp. 213-219, 2010.
56. C. Canto, Z. Gerhart-Hines, J. N. Feige et al., "AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity, " Nature, vol. 458, no. 7241, pp. 1056-1060, 2009.
57. R. Rafaeloff-Phail, L. Ding, L. Conner et al., "Biochemical regulation of mammalian AMP-activated protein kinase activity by NAD and NADH, " The Journal of Biological Chemistry, vol. 279, no. 51, pp. 52934-52939, 2004.
58. P. de Lange, P. Farina, M. Moreno et al., "Sequential changes in the signal transduction responses of skeletal muscle following food deprivation, " The FASEB Journal, vol. 20, no. 14, pp. 2579-2581, 2006.
59. D. Carling, "The AMP-activated protein kinase cascade-a unifying system for energy control, " Trends in Biochemical Sciences, vol. 29, no. 1, pp. 18-24, 2004.
60. S. Jager, C. Handschin, J. St-Pierre, and B. M. Spiegelman, "AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha, " Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 29, pp. 12017-12022, 2007.
61. I. Irrcher, V. Ljubicic, A. F. Kirwan, and D. A. Hood, "AMPactivated protein kinase-regulated activation of the PGC-1alpha promoter in skeletal muscle cells, " PloS One, vol. 3, no. 10, article e3614, 2008.
62. H. Zong, J. M. Ren, L. H. Young et al., "AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation, " Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 25, pp. 15983-15987, 2002.
63. B. J. Gurd, "Deacetylation of PGC-1alpha by SIRT1: importance for skeletal muscle function and exercise-induced mitochondrial biogenesis, " Applied Physiology, Nutrition, and Metabolism, vol. 36, no. 5, pp. 589-597, 2011.
64. J. A. Baur, K. J. Pearson, N. L. Price et al., "Resveratrol improves health and survival of mice on a high-calorie diet, " Nature, vol. 444, no. 7117, pp. 337-342, 2006.
65. N. L. Price, A. P. Gomes, A. J. Ling et al., "SIRT1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function, " Cell Metabolism, vol. 15, no. 5, pp. 675-690, 2012.
66. A. P. Gomes, N. L. Price, A. J. Ling et al., "Declining NAD(+) induces a pseudohypoxic state disrupting nuclearmitochondrial communication during aging, " Cell, vol. 155, no. 7, pp. 1624-1638, 2013.
67. M. Lagouge, C. Argmann, Z. Gerhart-Hines et al., "Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha, " Cell, vol. 127, no. 6, pp. 1109-1122, 2006.
68. M. Suwa, H. Nakano, and S. Kumagai, "Effects of chronic AICAR treatment on fiber composition, enzyme activity, UCP3, and PGC-1 in rat muscles, " Journal of Applied Physiology (Bethesda, Md. :1985), vol. 95, no. 3, pp. 960-968, 2003.
69. M. Fulco, Y. Cen, P. Zhao et al., "Glucose restriction inhibits skeletal myoblast differentiation by activating SIRT1 through AMPK-mediated regulation of Nampt, " Developmental Cell, vol. 14, no. 5, pp. 661-673, 2008.
70. R. M. Reznick, H. Zong, J. Li et al., "Aging-associated reductions in AMP-activated protein kinase activity and mitochondrial biogenesis, " Cell Metabolism, vol. 5, no. 2, pp. 151-156, 2007.
71. R. Bergeron, J. M. Ren, K. S. Cadman et al., "Chronic activation of AMP kinase results in NRF-1 activation and mitochondrial biogenesis, " American Journal of Physiology. Endocrinology and Metabolism, vol. 281, no. 6, pp. E1340-E1346, 2001.
72. W. Qiang, K. Weiqiang, Z. Qing, Z. Pengju, and L. Yi, "Aging impairs insulin-stimulated glucose uptake in rat skeletal muscle via suppressing AMPKalpha, " Experimental & Molecular Medicine, vol. 39, no. 4, pp. 535-543, 2007.
73. T. D. Pugh, M. W. Conklin, T. D. Evans et al., "A shift in energy metabolism anticipates the onset of sarcopenia in rhesus monkeys, " Aging Cell, vol. 12, no. 4, pp. 672-681, 2013.
74. J. Camacho-Pereira, M. G. Tarrago, C. C. Chini et al., "CD38 dictates age-related NAD decline and mitochondrial dysfunction through an SIRT3-dependent mechanism, " Cell Metabolism, vol. 23, no. 6, pp. 1127-1139, 2016.
75. H. Zhang, D. Ryu, Y. Wu et al., "NAD(+) repletion improves mitochondrial and stem cell function and enhances life span in mice, " Science, vol. 352, no. 6292, pp. 1436-1443, 2016.
76. T. Gabaldon and M. A. Huynen, "From endosymbiont to host-controlled organelle: The hijacking of mitochondrial protein synthesis and metabolism, " PLoS Computational Biology, vol. 3, no. 11, article e219, 2007.
77. S. E. Calvo and V. K. Mootha, "The mitochondrial proteome and human disease, " Annual Review of Genomics and Human Genetics, vol. 11, pp. 25-44, 2010.
78. J. B. Stewart and P. F. Chinnery, "The dynamics of mitochondrial DNA heteroplasmy: implications for human health and disease, " Nature Reviews. Genetics, vol. 16, no. 9, pp. 530-542, 2015.
79. V. Tiranti, A. Savoia, F. Forti et al., "Identification of the gene encoding the human mitochondrial RNA polymerase (h-mtRPOL) by cyberscreening of the expressed sequence tagsdatabase, " Human Molecular Genetics, vol. 6, no. 4, pp. 615-625, 1997.
80. M. Falkenberg, M. Gaspari, A. Rantanen, A. Trifunovic, N. G. Larsson, and C. M. Gustafsson, "Mitochondrial transcription factors B1 and B2 activate transcription of human mtDNA, " Nature Genetics, vol. 31, no. 3, pp. 289-294, 2002.
81. V. McCulloch, B. L. Seidel-Rogol, and G. S. Shadel, "A human mitochondrial transcription factor is related to RNA adenine methyltransferases and binds S-adenosylmethionine, " Molecular and Cellular Biology, vol. 22, no. 4, pp. 1116-1125, 2002.
82. C. M. Lee, S. S. Chung, J. M. Kaczkowski, R. Weindruch, and J. M. Aiken, "Multiple mitochondrial DNA deletions associated with age in skeletal muscle of rhesus monkeys, " Journal of Gerontology, vol. 48, no. 6, pp. B201-B205, 1993.
83. Y. Wang, Y. Michikawa, C. Mallidis et al., "Muscle-specific mutations accumulate with aging in critical human mtDNA control sites for replication, " Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 7, pp. 4022-4027, 2001.
84. M. Khaidakov, R. H. Heflich, M. G. Manjanatha, M. B. Myers, and A. Aidoo, "Accumulation of point mutations in mitochondrial DNA of aging mice, " Mutation Research, vol. 526, no. 1-2, pp. 1-7, 2003.
85. A. Herbst, J. W. Pak, D. McKenzie, E. Bua, M. Bassiouni, and J. M. Aiken, "Accumulation of mitochondrial DNA deletion mutations in aged muscle fibers: evidence for a causal role in muscle fiber loss, " The Journals of Gerontology. Series a, Biological Sciences and Medical Sciences, vol. 62, no. 3, pp. 235-245, 2007.
86. J. Wanagat, Z. Cao, P. Pathare, and J. M. Aiken, "Mitochondrial DNA deletion mutations colocalize with segmental electron transport system abnormalities, muscle fiber atrophy, fiber splitting, and oxidative damage in sarcopenia, " The FASEB Journal, vol. 15, no. 2, pp. 322-332, 2001.
87. J. M. Cooper, V. M. Mann, and A. H. Schapira, "Analyses of mitochondrial respiratory chain function and mitochondrial DNA deletion in human skeletal muscle: effect of ageing, " Journal of the Neurological Sciences, vol. 113, no. 1, pp. 91-98, 1992.
88. V. Pesce, A. Cormio, F. Fracasso, A. M. Lezza, P. Cantatore, and M. N. Gadaleta, "Age-related changes of mitochondrial DNA content and mitochondrial genotypic and phenotypic alterations in rat hind-limb skeletal muscles, " The Journals of Gerontology. Series a, Biological Sciences and Medical Sciences, vol. 60, no. 6, pp. 715-723, 2005.
89. M. Pinto and C. T. Moraes, "Mechanisms linking mtDNA damage and aging, " Free Radical Biology & Medicine, vol. 85, pp. 250-258, 2015.
90. M. Lagouge and N. G. Larsson, "The role of mitochondrial DNA mutations and free radicals in disease and ageing, " Journal of Internal Medicine, vol. 273, no. 6, pp. 529-543, 2013.
91. K. E. Conley, D. J. Marcinek, and J. Villarin, "Mitochondrial dysfunction and age, " Current Opinion in Clinical Nutrition and Metabolic Care, vol. 10, no. 6, pp. 688-692, 2007.
92. R. Barazzoni, K. R. Short, and K. S. Nair, "Effects of aging on mitochondrial DNA copy number and cytochrome c oxidase gene expression in rat skeletal muscle, liver, and heart, " The Journal of Biological Chemistry, vol. 275, no. 5, pp. 3343-3347, 2000.
93. F. J. Miller, F. L. Rosenfeldt, C. Zhang, A. W. Linnane, and P. Nagley, "Precise determination of mitochondrial DNA copy number in human skeletal and cardiac muscle by a PCRbased assay: lack of change of copy number with age, " Nucleic Acids Research, vol. 31, no. 11, article e61, 2003.
94. V. Pesce, A. Cormio, F. Fracasso et al., "Age-related mitochondrial genotypic and phenotypic alterations in human skeletal muscle, " Free Radical Biology & Medicine, vol. 30, no. 11, pp. 1223-1233, 2001.
95. K. Li, P. D. Neufer, and R. S. Williams, "Nuclear responses to depletion of mitochondrial DNA in human cells, " The American Journal of Physiology, vol. 269, no. 5, Part 1, pp. C1265-C1270, 1995.
96. N. D. Marchenko, A. Zaika, and U. M. Moll, "Death signal-induced localization of p53 protein to mitochondria. A potential role in apoptotic signaling, " The Journal of Biological Chemistry, vol. 275, no. 21, pp. 16202-16212, 2000.
97. Y. Yoshida, H. Izumi, T. Torigoe et al., "P53 physically interacts with mitochondrial transcription factor A and differentially regulates binding to damaged DNA, " Cancer Research, vol. 63, no. 13, pp. 3729-3734, 2003.
98. A. Saleem, H. N. Carter, S. Iqbal, and D. A. Hood, "Role of p53 within the regulatory network controlling muscle mitochondrial biogenesis, " Exercise and Sport Sciences Reviews, vol. 39, no. 4, pp. 199-205, 2011.
99. J. D. Bartlett, G. L. Close, B. Drust, and J. P. Morton, "The emerging role of p53 in exercise metabolism, " Sports Medicine, vol. 44, no. 3, pp. 303-309, 2014.
100. A. Saleem, P. J. Adhihetty, and D. A. Hood, "Role of p53 in mitochondrial biogenesis and apoptosis in skeletal muscle, " Physiological Genomics, vol. 37, no. 1, pp. 58-66, 2009.
101. R. J. Donahue, M. Razmara, J. B. Hoek, and T. B. Knudsen, "Direct influence of the p53 tumor suppressor on mitochondrial biogenesis and function, " The FASEB Journal, vol. 15, no. 3, pp. 635-644, 2001.
102. J. H. Park, J. Zhuang, J. Li, and P. M. Hwang, "p53 as guardian of the mitochondrial genome, " FEBS Letters, vol. 590, no. 7, pp. 924-934, 2016.
103. S. Matoba, J. G. Kang, W. D. Patino et al., "p53 regulates mitochondrial respiration, " Science, vol. 312, no. 5780, pp. 1650-1653, 2006.
104. K. Heyne, S. Mannebach, E. Wuertz, K. X. Knaup, M. Mahyar-Roemer, and K. Roemer, "Identification of a putative p53 binding sequence within the human mitochondrial genome, " FEBS Letters, vol. 578, no. 1-2, pp. 198-202, 2004.
105. A. Saleem and D. A. Hood, "Acute exercise induces tumour suppressor protein p53 translocation to the mitochondria and promotes a p53-Tfam-mitochondrial DNA complex in skeletal muscle, " The Journal of Physiology, vol. 591, no. 14, pp. 3625-3636, 2013.
106. S. H. Liang and M. F. Clarke, "Regulation of p53 localization, " European Journal of Biochemistry, vol. 268, no. 10, pp. 2779-2783, 2001.
107. J. Y. Park, P. Y. Wang, T. Matsumoto et al., "p53 improves aerobic exercise capacity and augments skeletal muscle mitochondrial DNA content, " Circulation Research, vol. 105, no. 7, pp. 705-712, 2009.
108. A. Safdar, K. Khrapko, J. M. Flynn et al., "Exercise-induced mitochondrial p53 repairs mtDNA mutations in mutator mice, " Skeletal Muscle, vol. 6, p. 7, 2016.
109. A. Saleem, S. Iqbal, Y. Zhang, and D. A. Hood, "Effect of p53 on mitochondrial morphology, import, and assembly in skeletal muscle, " American Journal of Physiology. Cell Physiology, vol. 308, no. 4, pp. C319-C329, 2015.
110. A. Saleem, H. N. Carter, and D. A. Hood, "p53 is necessary for the adaptive changes in cellular milieu subsequent to an acute bout of endurance exercise, " American Journal of Physiology. Cell Physiology, vol. 306, no. 3, pp. C241-C249, 2014.
111. K. Aquilano, S. Baldelli, B. Pagliei, S. M. Cannata, G. Rotilio, and M. R. Ciriolo, "p53 orchestrates the PGC-1alphamediated antioxidant response upon mild redox and metabolic imbalance, " Antioxidants & Redox Signaling, vol. 18, no. 4, pp. 386-399, 2013.
112. N. Sen, Y. K. Satija, and S. Das, "PGC-1alpha, a key modulator of p53, promotes cell survival upon metabolic stress, " Molecular Cell, vol. 44, no. 4, pp. 621-634, 2011.
113. M. M. Ziaaldini, E. Koltai, Z. Csende et al., "Exercise training increases anabolic and attenuates catabolic and apoptotic processes in aged skeletal muscle of male rats, " Experimental Gerontology, vol. 67, pp. 9-14, 2015.
114. J. Tamilselvan, G. Jayaraman, K. Sivarajan, and C. Panneerselvam, "Age-dependent upregulation of p53 and cytochrome c release and susceptibility to apoptosis in skeletal muscle fiber of aged rats: role of carnitine and lipoic acid, " Free Radical Biology & Medicine, vol. 43, no. 12, pp. 1656-1669, 2007.
115. L. Chung and Y. C. Ng, "Age-related alterations in expression of apoptosis regulatory proteins and heat shock proteins in rat skeletal muscle, " Biochimica et Biophysica Acta, vol. 1762, no. 1, pp. 103-109, 2006.
116. M. G. Edwards, R. M. Anderson, M. Yuan, C. M. Kendziorski, R. Weindruch, and T. A. Prolla, "Gene expression profiling of aging reveals activation of a p53-mediated transcriptional program, " BMC Genomics, vol. 8, no. 1, p. 80, 2007.
117. N. J. Maclaine and T. R. Hupp, "The regulation of p53 by phosphorylation: A model for how distinct signals integrate into the p53 pathway, " Aging (Albany, NY), vol. 1, no. 5, pp. 490-502, 2009.
118. G. He, Y. W. Zhang, J. H. Lee et al., "AMP-activated protein kinase induces p53 by phosphorylating MDMX and inhibiting its activity, " Molecular and Cellular Biology, vol. 34, no. 2, pp. 148-157, 2014.
119. R. G. Jones, D. R. Plas, S. Kubek et al., "AMP-activated protein kinase induces a p53-dependent metabolic checkpoint, " Molecular Cell, vol. 18, no. 3, pp. 283-293, 2005.
120. A. Philp and S. Schenk, "Unraveling the complexities of SIRT1-mediated mitochondrial regulation in skeletal muscle, " Exercise and Sport Sciences Reviews, vol. 41, no. 3, pp. 174-181, 2013.
121. H. Vaziri, S. K. Dessain, E. Ng Eaton et al., "hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase, " Cell, vol. 107, no. 2, pp. 149-159, 2001.
122. S. Baldelli and M. R. Ciriolo, "Altered S-nitrosylation of p53 is responsible for impaired antioxidant response in skeletal muscle during aging, " Aging (Albany, NY), vol. 8, no. 12, pp. 3450-3467, 2016.
123. E. Yakubovskaya, K. E. Guja, E. T. Eng et al., "Organization of the human mitochondrial transcription initiation complex, " Nucleic Acids Research, vol. 42, no. 6, pp. 4100-4112, 2014.
124. N. Gleyzer, K. Vercauteren, and R. C. Scarpulla, "Control of mitochondrial transcription specificity factors (TFB1M and TFB2M) by nuclear respiratory factors (NRF-1 and NRF-2) and PGC-1 family coactivators, " Molecular and Cellular Biology, vol. 25, no. 4, pp. 1354-1366, 2005.
125. N. G. Larsson, J. Wang, H. Wilhelmsson et al., "Mitochondrial transcription factor A is necessary for mtDNA maintenance and embryogenesis in mice, " Nature Genetics, vol. 18, no. 3, pp. 231-236, 1998.
126. Y. Shi, A. Dierckx, P. H. Wanrooij et al., "Mammalian transcription factor A is a core component of the mitochondrial transcription machinery, " Proceedings of the National Academy of Sciences of the United States of America, vol. 109, no. 41, pp. 16510-16515, 2012.
127. H. B. Ngo, J. T. Kaiser, and D. C. Chan, "The mitochondrial transcription and packaging factor Tfam imposes a U-turn on mitochondrial DNA, " Nature Structural & Molecular Biology, vol. 18, no. 11, pp. 1290-1296, 2011.
128. A. Rubio-Cosials, J. F. Sidow, N. Jimenez-Menendez et al., "Human mitochondrial transcription factor A induces a U-turn structure in the light strand promoter, " Nature Structural & Molecular Biology, vol. 18, no. 11, pp. 1281-1289, 2011.
129. R. P. Fisher, T. Lisowsky, M. A. Parisi, and D. A. Clayton, "DNA wrapping and bending by a mitochondrial high mobility group-like transcriptional activator protein, " The Journal of Biological Chemistry, vol. 267, no. 5, pp. 3358-3367, 1992.
130. D. F. Bogenhagen, "Mitochondrial DNA nucleoid structure, " Biochimica et Biophysica Acta, vol. 1819, no. 9-10, pp. 914-920, 2012.
131. H. B. Ngo, G. A. Lovely, R. Phillips, and D. C. Chan, "Distinct structural features of TFAM drive mitochondrial DNA packaging versus transcriptional activation, " Nature Communications, vol. 5, p. 3077, 2014.
132. N. G. Larsson, A. Oldfors, E. Holme, and D. A. Clayton, "Low levels of mitochondrial transcription factor A in mitochondrial DNA depletion, " Biochemical and Biophysical Research Communications, vol. 200, no. 3, pp. 1374-1381, 1994.
133. M. I. Ekstrand, M. Falkenberg, A. Rantanen et al., "Mitochondrial transcription factor A regulates mtDNA copy number in mammals, " Human Molecular Genetics, vol. 13, no. 9, pp. 935-944, 2004.
134. M. Collu-Marchese, M. Shuen, M. Pauly, A. Saleem, and D. A. Hood, "The regulation of mitochondrial transcription factor A (Tfam) expression during skeletal muscle cell differentiation, " Bioscience Reports, vol. 35, no. 3, 2015.
135. H. N. Carter and D. A. Hood, "Contractile activity-induced mitochondrial biogenesis and mTORC1, " American Journal of Physiology. Cell Physiology, vol. 303, no. 5, pp. C540-C547, 2012.
136. J. W. Gordon, A. A. Rungi, H. Inagaki, and D. A. Hood, "Effects of contractile activity on mitochondrial transcription factor A expression in skeletal muscle, " Journal of Applied Physiology (Bethesda, Md. :1985), vol. 90, no. 1, pp. 389-396, 2001.
137. R. Y. Lai, V. Ljubicic, D. D'Souza, and D. A. Hood, "Effect of chronic contractile activity on mRNA stability in skeletal muscle, " American Journal of Physiology. Cell Physiology, vol. 299, no. 1, pp. C155-C163, 2010.
138. H. Pilegaard, B. Saltin, and P. D. Neufer, "Exercise induces transient transcriptional activation of the PGC-1alpha genein human skeletal muscle, " The Journal of Physiology, vol. 546, Part 3, pp. 851-858, 2003.
139. G. Uguccioni and D. A. Hood, "The importance of PGC-1alpha in contractile activity-induced mitochondrial adaptations, " American Journal of Physiology. Endocrinology and Metabolism, vol. 300, no. 2, pp. E361-E371, 2011.
140. H. C. Lee, P. H. Yin, C. Y. Lu, C. W. Chi, and Y. H. Wei, "Increase of mitochondria and mitochondrial DNA in response to oxidative stress in human cells, " The Biochemical Journal, vol. 348, Part 2, pp. 425-432, 2000.
141. A. Wredenberg, R. Wibom, H. Wilhelmsson et al., "Increased mitochondrial mass in mitochondrial myopathy mice, " Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 23, pp. 15066-15071, 2002.
142. A. M. Lezza, V. Pesce, A. Cormio et al., "Increased expression of mitochondrial transcription factor A and nuclear respiratory factor-1 in skeletal muscle from aged human subjects, " FEBS Letters, vol. 501, no. 1, pp. 74-78, 2001.
143. H. Chen, M. Vermulst, Y. E. Wang et al., "Mitochondrial fusion is required for mtDNA stability in skeletal muscle and tolerance of mtDNA mutations, " Cell, vol. 141, no. 2, pp. 280-289, 2010.
144. S. Cipolat, O. Martins de Brito, B. Dal Zilio, and L. Scorrano, "OPA1 requires mitofusin 1 to promote mitochondrial fusion, " Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 45, pp. 15927-15932, 2004.
145. O. C. Loson, Z. Song, H. Chen, and D. C. Chan, "Fis1, Mff, MiD49, and MiD51 mediate Drp1 recruitment in mitochondrial fission, " Molecular Biology of the Cell, vol. 24, no. 5, pp. 659-667, 2013.
146. S. Mai, M. Klinkenberg, G. Auburger, J. Bereiter-Hahn, and M. Jendrach, "Decreased expression of Drp1 and Fis1 mediates mitochondrial elongation in senescent cells and enhances resistance to oxidative stress through PINK1, " Journal of Cell Science, vol. 123, Part 6, pp. 917-926, 2010.
147. A. M. Joseph, P. J. Adhihetty, T. W. Buford et al., "The impact of aging on mitochondrial function and biogenesis pathways in skeletal muscle of sedentary high-and lowfunctioning elderly individuals, " Aging Cell, vol. 11, no. 5, pp. 801-809, 2012.
148. D. Sebastian, E. Sorianello, J. Segales et al., "Mfn2 deficiency links age-related sarcopenia and impaired autophagy to activation of an adaptive mitophagy pathway, " The EMBO Journal, vol. 35, no. 15, pp. 1677-1693, 2016.
149. A. M. Joseph, P. J. Adhihetty, N. R. Wawrzyniak et al., "Dysregulation of mitochondrial quality control processes contribute to sarcopenia in a mouse model of premature aging, " PLoS One, vol. 8, no. 7, article e69327, 2013.
150. G. Distefano, R. A. Standley, J. J. Dube et al., "Chronological age does not influence ex-vivo mitochondrial respiration and quality control in skeletal muscle, " The Journals of Gerontology. Series a, Biological Sciences and Medical Sciences, vol. 72, no. 4, pp. 535-542, 2017.
151. E. Koltai, N. Hart, A. W. Taylor et al., "Age-associated declines in mitochondrial biogenesis and protein quality control factors are minimized by exercise training, " American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, vol. 303, no. 2, pp. R127-R134, 2012.
152. H. Tai, Z. Wang, H. Gong et al., "Autophagy impairment with lysosomal and mitochondrial dysfunction is an important characteristic of oxidative stress-induced senescence, " Autophagy, vol. 13, no. 1, pp. 99-113, 2017.
153. A. M. Cuervo and J. F. Dice, "Age-related decline in chaperone-mediated autophagy, " The Journal of Biological Chemistry, vol. 275, no. 40, pp. 31505-31513, 2000.
154. A. Terman, H. Dalen, J. W. Eaton, J. Neuzil, and U. T. Brunk, "Mitochondrial recycling and aging of cardiac myocytes: The role of autophagocytosis, " Experimental Gerontology, vol. 38, no. 8, pp. 863-876, 2003.
155. L. M. Baehr, D. W. West, G. Marcotte et al., "Age-related deficits in skeletal muscle recovery following disuse are associated with neuromuscular junction instability and ER stress, not impaired protein synthesis, " Aging (Albany, NY), vol. 8, no. 1, pp. 127-146, 2016.
156. K. Sakuma, M. Kinoshita, Y. Ito, M. Aizawa, W. Aoi, and A. Yamaguchi, "p62/SQSTM1 but not LC3 is accumulated in sarcopenic muscle of mice, " Journal of Cachexia, Sarcopenia and Muscle, vol. 7, no. 2, pp. 204-212, 2016.
157. A. M. Fritzen, C. Frosig, J. Jeppesen et al., "Role of AMPK in regulation of LC3 lipidation as a marker of autophagy in skeletal muscle, " Cellular Signalling, vol. 28, no. 6, pp. 663-674, 2016.
158. Z. White, J. Terrill, R. B. White et al., "Voluntary resistance wheel exercise from mid-life prevents sarcopenia and increases markers of mitochondrial function and autophagy in muscles of old male and female C57BL/6J mice, " Skeletal Muscle, vol. 6, no. 1, p. 45, 2016.
159. D. W. Russ, J. Krause, A. Wills, and R. Arreguin, ""SR stress" in mixed hindlimb muscles of aging male rats, " Biogerontology, vol. 13, no. 5, pp. 547-555, 2012.
160. A. Rana, M. Rera, and D. W. Walker, "Parkin overexpression during aging reduces proteotoxicity, alters mitochondrial dynamics, and extends lifespan, " Proceedings of the National Academy of Sciences of the United States of America, vol. 110, no. 21, pp. 8638-8643, 2013.
161. A. L. Bujak, J. D. Crane, J. S. Lally et al., "AMPK activation of muscle autophagy prevents fasting-induced hypoglycemia and myopathy during aging, " Cell Metabolism, vol. 21, no. 6, pp. 883-890, 2015.
162. H. J. Shin, H. Kim, S. Oh et al., "AMPK-SKP2-CARM1 signalling cascade in transcriptional regulation of autophagy, " Nature, vol. 534, no. 7608, pp. 553-557, 2016.
163. R. Kiffin, S. Kaushik, M. Zeng et al., "Altered dynamics of the lysosomal receptor for chaperone-mediated autophagy with age, " Journal of Cell Science, vol. 120, Part 5, pp. 782-791, 2007.
164. M. A. Bonelli, S. Desenzani, G. Cavallini et al., "Low-level caloric restriction rescues proteasome activity and Hsc70 level in liver of aged rats, " Biogerontology, vol. 9, no. 1, pp. 1-10, 2008.
165. A. Vasilaki, F. McArdle, L. M. Iwanejko, and A. McArdle, "Adaptive responses of mouse skeletal muscle to contractile activity: The effect of age, " Mechanisms of Ageing and Development, vol. 127, no. 11, pp. 830-839, 2006.
166. M. F. O'Leary, A. Vainshtein, S. Iqbal, O. Ostojic, and D. A. Hood, "Adaptive plasticity of autophagic proteins to denervation in aging skeletal muscle, " American Journal of Physiology. Cell Physiology, vol. 304, no. 5, pp. C422-C430, 2013.
167. S. E. Wohlgemuth, A. Y. Seo, E. Marzetti, H. A. Lees, and C. Leeuwenburgh, "Skeletal muscle autophagy and apoptosis during aging: effects of calorie restriction and life-longexercise, " Experimental Gerontology, vol. 45, no. 2, pp. 138-148, 2010.
168. A. M. Joseph, V. Ljubicic, P. J. Adhihetty, and D. A. Hood, "Biogenesis of the mitochondrial Tom40 channel in skeletal muscle from aged animals and its adaptability to chronic contractile activity, " American Journal of Physiology. Cell Physiology, vol. 298, no. 6, pp. C1308-C1314, 2010.
169. C. Kang, E. Chung, G. Diffee, and L. L. Ji, "Exercise training attenuates aging-associated mitochondrial dysfunction in rat skeletal muscle: role of PGC-1alpha, " Experimental Gerontology, vol. 48, no. 11, pp. 1343-1350, 2013.
170. A. C. Betik, M. M. Thomas, K. J. Wright, C. D. Riel, and R. T. Hepple, "Exercise training from late middle age until senescence does not attenuate the declines in skeletal muscle aerobic function, " American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, vol. 297, no. 3, pp. R744-R755, 2009.
171. A. R. Konopka, M. D. Douglass, L. A. Kaminsky et al., "Molecular adaptations to aerobic exercise training in skeletal muscle of older women, " The Journals of Gerontology. Series a, Biological Sciences and Medical Sciences, vol. 65, no. 11, pp. 1201-1207, 2010.
172. G. C. Rowe, R. El-Khoury, I. S. Patten, P. Rustin, and Z. Arany, "PGC-1alpha is dispensable for exercise-induced mitochondrial biogenesis in skeletal muscle, " PloS One, vol. 7, no. 7, article e41817, 2012.
173. S. Zampieri, L. Pietrangelo, S. Loefler et al., "Lifelong physical exercise delays age-associated skeletal muscle decline, " The Journals of Gerontology. Series a, Biological Sciences and Medical Sciences, vol. 70, no. 2, pp. 163-173, 2015.
174. R. Garcia-Valles, M. C. Gomez-Cabrera, L. Rodriguez-Manas et al., "Life-long spontaneous exercise does not prolong lifespan but improves health span in mice, " Longevity & Healthspan, vol. 2, no. 1, p. 14, 2013.
175. N. T. Broskey, C. Greggio, A. Boss et al., "Skeletal muscle mitochondria in the elderly: effects of physical fitness and exercise training, " The Journal of Clinical Endocrinology and Metabolism, vol. 99, no. 5, pp. 1852-1861, 2014.
176. S. Melov, M. A. Tarnopolsky, K. Beckman, K. Felkey, and A. Hubbard, "Resistance exercise reverses aging in human skeletal muscle, " PloS One, vol. 2, no. 5, article e465, 2007.
177. K. E. Yarasheski, J. Pak-Loduca, D. L. Hasten, K. A. Obert, M. B. Brown, and D. R. Sinacore, "Resistance exercise training increases mixed muscle protein synthesis rate in frail women and men
178. D. I. Ogborn, B. R. McKay, J. D. Crane et al., "Effects of age and unaccustomed resistance exercise on mitochondrial transcript and protein abundance in skeletal muscle of men, " American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, vol. 308, no. 8, pp. R734-R741, 2015.
179. K. D. Flack, B. M. Davy, M. DeBerardinis et al., "Resistance exercise training and in vitro skeletal muscle oxidative capacity in older adults, " Physiological Reports, vol. 4, no. 13, 2016.
180. N. P. Greene, D. E. Lee, J. L. Brown et al., "Mitochondrial quality control, promoted by PGC-1alpha, is dysregulated by Western diet-induced obesity and partially restored by moderate physical activity in mice, " Physiological Reports, vol. 3, no. 7, 2015.
181. J. S. Ju, S. I. Jeon, J. Y. Park et al., "Autophagy plays a role in skeletal muscle mitochondrial biogenesis in an endurance exercise-trained condition, " The Journal of Physiological Sciences, vol. 66, no. 5, pp. 417-430, 2016.
182. Z. Bori, Z. Zhao, E. Koltai et al., "The effects of aging, physical training, and a single bout of exercise on mitochondrial protein expression in human skeletal muscle, " Experimental Gerontology, vol. 47, no. 6, pp. 417-424, 2012.
183. S. Lee, M. Kim, W. Lim, T. Kim, and C. Kang, "Strenuous exercise induces mitochondrial damage in skeletal muscle of old mice, " Biochemical and Biophysical Research Communications, vol. 461, no. 2, pp. 354-360, 2015.
184. M. J. Drummond, O. Addison, L. Brunker et al., "Downregulation of E3 ubiquitin ligases and mitophagy-related genes in skeletal muscle of physically inactive, frail older women: A cross-sectional comparison, " The Journals of Gerontology. Series a, Biological Sciences and Medical Sciences, vol. 69, no. 8, pp. 1040-1048, 2014.
185. Y. A. Kim, Y. S. Kim, and W. Song, "Autophagic response to a single bout of moderate exercise in murine skeletal muscle, " Journal of Physiology and Biochemistry, vol. 68, no. 2, pp. 229-235, 2012.
186. C. Schwalm, C. Jamart, N. Benoit et al., "Activation of autophagy in human skeletal muscle is dependent on exercise intensity and AMPK activation, " The FASEB Journal, vol. 29, no. 8, pp. 3515-3526, 2015.
187. A. Vainshtein, L. D. Tryon, M. Pauly, and D. A. Hood, "Role of PGC-1alpha during acute exercise-induced autophagy and mitophagy in skeletal muscle, " American Journal of Physiology. Cell Physiology, vol. 308, no. 9, pp. C710-C719, 2015.
188. A. Vainshtein, E. M. A. Desjardins, A. Armani, M. Sandri, and D. A. Hood, "PGC-1 alpha modulates denervationinduced mitophagy in skeletal muscle, " Skeletal Muscle, vol. 5, no. 1, p. 9, 2015.
189. S. M. Garvey, D. W. Russ, M. B. Skelding, J. E. Dugle, and N. K. Edens, "Molecular and metabolomic effects of voluntary running wheel activity on skeletal muscle in late middleaged rats, " Physiological Reports, vol. 3, no. 2, 2015.
190. Y. A. Kim, Y. S. Kim, S. L. Oh, H. J. Kim, and W. Song, "Autophagic response to exercise training in skeletal muscle with age, " Journal of Physiology and Biochemistry, vol. 69, no. 4, pp. 697-705, 2013.
191. C. S. Fry, M. J. Drummond, E. L. Glynn et al., "Skeletal muscle autophagy and protein breakdown following resistance exercise are similar in younger and older adults, " The Journals of Gerontology. Series a, Biological Sciences and Medical Sciences, vol. 68, no. 5, pp. 599-607, 2013.
192. J. M. Dickinson, P. T. Reidy, D. M. Gundermann et al., "The impact of postexercise essential amino acid ingestion on the ubiquitin proteasome and autophagosomal-lysosomal systems in skeletal muscle of older men, " Journal of Applied Physiology (Bethesda, Md. :1985), vol. 122, no. 3, pp. 620-630, 2017.
193. L. Luo, A. M. Lu, Y. Wang et al., "Chronic resistance training activates autophagy and reduces apoptosis of muscle cells by modulating IGF-1 and its receptors, Akt/mTOR and Akt/ FOXO3a signaling in aged rats, " Experimental Gerontology, vol. 48, no. 4, pp. 427-436, 2013.
194. G. Mansueto, A. Armani, C. Viscomi et al., "Transcription factor EB controls metabolic flexibility during exercise, " Cell Metabolism, vol. 25, no. 1, pp. 182-196, 2017.