The role of mitochondria in aging

Journal of Clinical Investigation

Volumn 123, Issue 3, 2013, Pages 951-957

  Bratic, Ana ^a,b   Larsson, Nils Göran ^a,b  

^a MAX PLANCK INSTITUTE FOR BIOLOGY OF AGEING   (Germany)

^b KAROLINSKA INSTITUTE   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE TRIPHOSPHATE; FREE RADICAL; HELICASE; MITOCHONDRIAL DNA; PROTON TRANSPORTING ADENOSINE TRIPHOSPHATE SYNTHASE; RIBOSOME RNA; TRANSFER RNA;

AGING; ALOPECIA; ANEMIA; APOPTOSIS; CARDIOMYOPATHY; CELL CYCLE PROGRESSION; DNA DAMAGE; GENE DELETION; GENE SEGREGATION; GENOTYPE; HAIR LOSS; HEARING IMPAIRMENT; HETEROPLASMY; INSULIN RESISTANCE; KYPHOSIS; LIFE EXTENSION; LIFESPAN; MITOCHONDRIAL GENOME; MITOCHONDRIAL MYOPATHY; MITOCHONDRIAL RESPIRATION; MITOCHONDRION; MITOSIS; MUTAGENESIS; NONHUMAN; OXIDATIVE PHOSPHORYLATION; OXIDATIVE STRESS; PHENOTYPE; POINT MUTATION; PREMATURE AGING; PRIORITY JOURNAL; REVIEW; SOMATIC MUTATION; SUBFERTILITY; WEIGHT REDUCTION;

AGING; ANIMALS; CELL AGING; DNA, MITOCHONDRIAL; FREE RADICALS; HUMANS; MITOCHONDRIA; MUTAGENESIS; MUTATION; SIGNAL TRANSDUCTION;

EID: 84874591240     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI64125     Document Type: Review

References (125)

1. Harman D. Aging: a theory based on free radical and radiation chemistry. J Gerontol. 1956;11(3):298-300.
2. Villeponteau B. The heterochromatin loss model of aging. Exp Gerontol. 1997;32(4-5):383-394. (Pubitemid 27366477)
3. Kirkwood TB. Evolution of ageing. Nature. 1977; 270(5635):301-304.
4. Campisi J. The biology of replicative senescence. Eur J Cancer. 1997;33(5):703-709.
5. Hamilton WD. The moulding of senescence by natural selection. J Theor Biol. 1966;12(1):12-45.
6. Fraga CG, Shigenaga MK, Park JW, Degan P, Ames BN. Oxidative damage to DNA during aging: 8-hydroxy-2′-deoxyguanosine in rat organ DNA and urine. Proc Natl Acad Sci U S A. 1990;87(12):4533-4537.
7. Stadtman ER. Protein oxidation and aging. Science. 1992;257(5074):1220- 1224.
8. Marnett LJ, et al. Naturally occurring carbonyl compounds are mutagens in Salmonella tester strain TA104. Mutat Res. 1985;148(1-2):25-34. (Pubitemid 15151659)
9. Balaban RS, Nemoto S, Finkel T. Mitochondria, oxidants, and aging. Cell. 2005;120(4):483-495. (Pubitemid 40269763)
10. Schapira AH. Mitochondrial diseases. Lancet. 2012; 379(9828):1825-1834.
11. Müftüoglu M, et al. Mitochondrial complex I and IV activities in leukocytes from patients with parkin mutations. Mov Disord. 2004;19(5):544-548.
12. Grünewald A, et al. Mutant Parkin impairs mitochondrial function and morphology in human fibroblasts. PLoS One. 2010;5(9):e12962.
13. Larsson NG, et al. Mitochondrial transcription factor A is necessary for mtDNA maintenance and embryogenesis in mice. Nat Genet. 1998;18(3):231-236.
14. Shigenaga MK, Hagen TM, Ames BN. Oxidative damage and mitochondrial decay in aging. Proc Natl Acad Sci U S A. 1994;91(23):10771-10778. (Pubitemid 24349567)
15. Herbener G. A morphometric study of age-dependent changes in mitochondrial populations of mouse liver and heart. J Gerontol. 1976;31(1):8-12.
16. Stocco DM, Hutson JC. Quantitation of mitochondrial DNA and protein in the liver of Fischer 344 rats during aging. J Gerontol. 1978;33(6):802-809. (Pubitemid 9064611)
17. Yen T-C, Chen Y-S, King K-L, Yeh S-H, Wei Y-H. Liver mitochondrial respiratory functions decline with age. Biochem Biophys Res Commun. 1989; 165(3):994-1003. (Pubitemid 20029807)
18. Tauchi H, Sato T. Age changes in size and number of mitochondria of human hepatic cells. J Gerontol. 1968;23(4):454-461.
19. Stocco DM, Cascarano J, Wilson MA. Quantitation of mitochondrial DNA, RNA, and protein in starved and starved-refed rat liver. J Cell Physiol. 1977; 90(2):295-306. (Pubitemid 8051492)
20. Short KR, et al. Decline in skeletal muscle mitochondrial function with aging in humans. Proc Natl Acad Sci U S A. 2005;102(15):5618-5623. (Pubitemid 40530306)
21. Ojaimi J, Masters CL, Opeskin K, McKelvie P, Byrne E. Mitochondrial respiratory chain activity in the human brain as a function of age. Mech Ageing Dev. 1999;111(1):39-47. (Pubitemid 29486435)
22. Brierley EJ, Johnson MA, James OF, Turnbull DM. Mitochondrial involvement in the ageing process. Facts and controversies. Mol Cell Biochem. 1997; 174(1-2):325-328. (Pubitemid 27404209)
23. Yan LJ, Sohal RS. Mitochondrial adenine nucleotide translocase is modified oxidatively during aging. Proc Natl Acad Sci U S A. 1998;95(22):12896-12901. (Pubitemid 28509494)
24. Liu J, Killilea DW, Ames BN. Age-associated mitochondrial oxidative decay: improvement of carnitine acetyltransferase substrate-binding affinity and activity in brain by feeding old rats acetyl-Lcarnitine and/or R-alpha -lipoic acid. Proc Natl Acad Sci U S A. 2002;99(4):1876-1881. (Pubitemid 34168982)
25. Benzi G, et al. The mitochondrial electron transfer alteration as a factor involved in the brain aging. Neurobiol Aging. 1992;13(3):361-368.
26. Lenaz G, et al. Mitochondrial complex I defects in aging. Mol Cell Biochem. 1997;174(1-2):329-333. (Pubitemid 27404210)
27. Manczak M, Jung Y, Park BS, Partovi D, Reddy PH. Time-course of mitochondrial gene expressions in mice brains: implications for mitochondrial dysfunction, oxidative damage, and cytochrome c in aging. J Neurochem. 2005;92(3):494-504. (Pubitemid 40189453)
28. Navarro A, Boveris A. The mitochondrial energy transduction system and the aging process. Am J Physiol Cell Physiol. 2007;292(2):C670-C686.
29. Picard M, et al. Mitochondrial functional impairment with aging is exaggerated in isolated mitochondria compared to permeabilized myofibers. Aging Cell. 2010;9(6):1032-1046.
30. Evans WJ. Protein nutrition, exercise and aging. J Am Coll Nutr. 2004;23(6 suppl):601S-609S. (Pubitemid 40096748)
31. Knuever J, et al. Thyrotropin-releasing hormone controls mitochondrial biology in human epidermis. J Clin Endocrinol Metab. 2012;97(3):978-986.
32. Weitzel J, Iwen K, Seitz H. Regulation of mitochondrial biogenesis by thyroid hormone. Exp Physiol. 2003;88(1):121-128. (Pubitemid 36150065)
33. Scheller K, Sekeris CE. The effects of steroid hormones on the transcription of genes encoding enzymes of oxidative phosphorylation. Exp Physiol. 2003;88(1):129-140. (Pubitemid 36150066)
34. Chen J-Q, Cammarata PR, Baines CP, Yager JD. Regulation of mitochondrial respiratory chain biogenesis by estrogens/estrogen receptors and physiological, pathological and pharmacological implications. Biochim Biophys Acta. 2009;1793(10):1540-1570.
35. Fernandez-Vizarra E, Enriquez JA, Pérez-Martos A, Montoya J, Fernandez-Silva P. Mitochondrial gene expression is regulated at multiple levels and differentially in the heart and liver by thyroid hormones. Curr Genet. 2008;54(1):13-22.
36. Radák Z, Zhao Z, Koltai E, Ohno H, Atalay M. Oxygen consumption and usage during physical exercise: the balance between oxidative stress and ROS-dependent adaptive signaling [published online ahead of print: November 16, 2012]. Antioxid Redox Signal. doi:10.1089/ars.2011.4498
37. Nisoli E. Calorie restriction promotes mitochondrial biogenesis by inducing the expression of eNOS. Science. 2005;310(5746):314-317. (Pubitemid 41457197)
38. Corral-Debrinski M, et al. Mitochondrial DNA deletions in human brain: regional variability and increase with advanced age. Nat Genet. 1992;2(4):324-329.
39. Yen T-C, Su J-H, King K-L, Wei Y-H. Ageing-associated 5 kb deletion in human liver mitochondrial DNA. Biochem Biophys Res Commun. 1991;178(1):124-131.
40. Fayet G, et al. Ageing muscle: clonal expansions of mitochondrial DNA point mutations and deletions cause focal impairment of mitochondrial function. Neuromuscul Disord. 2002;12(5):484-493. (Pubitemid 34556709)
41. Taylor RW, et al. Mitochondrial DNA mutations in human colonic crypt stem cells. J Clin Invest. 2003; 112(9):1351-1360. (Pubitemid 38057689)
42. Larsson N-G. Somatic mitochondrial DNA mutations in mammalian aging. Annu Rev Biochem. 2010; 79:683-706.
43. Stewart JB, et al. Strong purifying selection in transmission of mammalian mitochondrial DNA. PloS Biol. 2008;6(1):e10.
44. Stewart JB, Freyer C, Elson JL, Larsson N-G. Purifying selection of mtDNA and its implications for understanding evolution and mitochondrial disease. Nat Rev Genet. 2008;9(9):657-662.
45. Ameur A, et al. Ultra-deep sequencing of mouse mitochondrial DNA: mutational patterns and their origins. PLoS Genet. 2011;7(3):e1002028.
46. Clayton DA. Replication of animal mitochondrial DNA. Cell. 1982;28(4):693-705. (Pubitemid 12084326)
47. Hayashi J, et al. Introduction of disease-related mitochondrial DNA deletions into HeLa cells lacking mitochondrial DNA results in mitochondrial dysfunction. Proc Natl Acad Sci U S A. 1991; 88(23):10614-10618. (Pubitemid 21915887)
48. Chomyn A, et al. MELAS mutation in mtDNA binding site for transcription termination factor causes defects in protein synthesis and in respiration but no change in levels of upstream and downstream mature transcripts. Proc Natl Acad Sci U S A. 1992; 89(10):4221-4225.
49. Holme E, et al. Multiple symmetric lipomas with high levels of mtDNA with the tRNA(Lys) A->G(8344) mutation as the only manifestation of disease in a carrier of myoclonus epilepsy and ragged-red fibers (MERRF) syndrome. Am J Hum Genet. 1993;52(3):551-556. (Pubitemid 23311325)
50. Durham SE, Samuels DC, Chinnery PF. Is selection required for the accumulation of somatic mitochondrial DNA mutations in post-mitotic cells? Neuromuscul Disord. 2006;16(6):381-386. (Pubitemid 43866496)
51. Elson JL, Samuels DC, Turnbull DM, Chinnery PF. Random intracellular drift explains the clonal expansion of mitochondrial DNA mutations with age. Am J Hum Genet. 2001;68(3):802-806. (Pubitemid 32202775)
52. Bender A, et al. High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease. Nat Genet. 2006;38(5):515-517.
53. Schwarze SR, Lee CM, Chung SS, Roecker EB, Weindruch R, Aiken JM. High levels of mitochondrial DNA deletions in skeletal muscle of old rhesus monkeys. Mech Ageing Dev. 1995;83(2):91-101.
54. Kraytsberg Y, et al. Mitochondrial DNA deletions are abundant and cause functional impairment in aged human substantia nigra neurons. Nat Genet. 2006;38(5):518-520.
55. Müller-Höcker J. Cytochrome-c-oxidase deficient cardiomyocytes in the human heart - an age-related phenomenon. A histochemical ultracytochemical study. Am J Pathol. 1989;134(5):1167-1173. (Pubitemid 19142900)
56. Müller-Höcker J. Cytochrome c oxidase deficient fibres in the limb muscle and diaphragm of man without muscular disease: An age-related alteration. J Neurol Sci. 1990;100(1-2):14-21.
57. Cottrell DA, et al. Cytochrome c oxidase deficient cells accumulate in the hippocampus and choroid plexus with age. Neurobiol Aging. 2001;22(2):265-272. (Pubitemid 32162975)
58. Trifunovic A, et al. Premature ageing in mice expressing defective mitochondrial DNA polymerase. Nature. 2004;429(6990):417-423. (Pubitemid 38715133)
59. Kujoth GC. Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging. Science. 2005;309(5733):481-484.
60. Vermulst M, et al. DNA deletions and clonal mutations drive premature aging in mitochondrial mutator mice. Nat Genet. 2008;40(4):392-394. (Pubitemid 351450885)
61. Williams SL, et al. The mtDNA mutation spectrum of the progeroid Polg mutator mouse includes abundant control region multimers. Cell Metab. 2010;12(6):675-682.
62. Park CB, Larsson N-G. Mitochondrial DNA mutations in disease and aging. J Cell Biol. 2011; 193(5):809-818.
63. Edgar D, et al. Random point mutations with major effects on protein-coding genes are the driving force behind premature aging in mtDNA mutator mice. Cell Metab. 2009;10(2):131-138.
64. Tyynismaa H, et al. Mutant mitochondrial helicase Twinkle causes multiple mtDNA deletions and a late-onset mitochondrial disease in mice. Proc Natl Acad Sci U S A. 2005;102(49):17687-17692. (Pubitemid 41803558)
65. Ahlqvist KJ, et al. Somatic progenitor cell vulnerability to mitochondrial DNA mutagenesis underlies progeroid phenotypes in Polg mutator mice. Cell Metab. 2012;15(1):100-109.
66. Trifunovic A, et al. Somatic mtDNA mutations cause aging phenotypes without affecting reactive oxygen species production. Proc Natl Acad Sci U S A. 2005;102(50):17993-17998. (Pubitemid 41798490)
67. Orr WC, Sohal RS. Extension of life-span by overexpression of superoxide dismutase and catalase in Drosophila melanogaster. Science. 1994; 263(5150):1128-1130. (Pubitemid 24105957)
68. Mockett RJ, Bayne A-CV, Kwong LK, Orr WC, Sohal RS. Ectopic expression of catalase in Drosophila mitochondria increases stress resistance but not longevity. Free Radic Biol Med. 2003;34(2):207-217. (Pubitemid 36084324)
69. Orr WC, Mockett RJ, Benes JJ, Sohal RS. Effects of overexpression of copper-zinc and manganese superoxide dismutases, catalase, and thioredoxin reductase genes on longevity in Drosophila melanogaster. J Biol Chem. 2003;278(29):26418-26422. (Pubitemid 36876781)
70. Zhang Y, et al. Mice deficient in both Mn superoxide dismutase and glutathione peroxidase-1 have increased oxidative damage and a greater incidence of pathology but no reduction in longevity. J Gerontol A Biol Sci Med Sci. 2009;64A(12):1212-1220.
71. Van Raamsdonk JM, Hekimi S. Deletion of the mitochondrial superoxide dismutase sod-2 extends lifespan in Caenorhabditis elegans. PLoS Genet. 2009;5(2):e1000361.
72. Doonan R, et al. Against the oxidative damage theory of aging: superoxide dismutases protect against oxidative stress but have little or no effect on life span in Caenorhabditis elegans. Genes Dev. 2008; 22(23):3236-3241.
73. Kayser EB, Morgan PG, Hoppel CL, Sedensky MM. Mitochondrial expression and function of GAS-1 in Caenorhabditis elegans. J Biol Chem. 2001; 276(23):20551-20558.
74. Duttaroy A, Paul A, Kundu M, Belton A. A Sod2 null mutation confers severely reduced adult life span in Drosophila. Genetics. 2003;165(4):2295-2299. (Pubitemid 38040309)
75. Li Y, et al. Dilated cardiomyopathy and neonatal lethality in mutant mice lacking manganese superoxide dismutase. Nat Genet. 1995;11(4):376-381.
76. Lebovitz RM, et al. Neurodegeneration, myocardial injury, and perinatal death in mitochondrial superoxide dismutase-deficient mice. Proc Natl Acad Sci U S A. 1996;93(18):9782-9787. (Pubitemid 26296686)
77. Sun J, Folk D, Bradley TJ, Tower J. Induced overexpression of mitochondrial Mn-superoxide dismutase extends the life span of adult Drosophila melanogaster. Genetics. 2002;161(2):661-672. (Pubitemid 34705407)
78. Mockett RJ, Sohal BH, Sohal RS. Expression of multiple copies of mitochondrially targeted catalase or genomic Mn superoxide dismutase transgenes does not extend the life span of Drosophila melanogaster. Free Radic Biol Med. 2010;49(12):2028-2031.
79. O'donnell E, Lynch M. Dietary antioxidant supplementation reverses age-related neuronal changes. Neurobiol Aging. 1998;19(5):461-467. (Pubitemid 29065495)
80. Alvarado C, et al. Dietary supplementation with antioxidants improves functions and decreases oxidative stress of leukocytes from prematurely aging mice. Nutrition. 2006;22(7-8):767-777. (Pubitemid 43947509)
81. Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C. Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Cochrane Database Syst Rev. 2012;3:CD007176.
82. Walker C. Antioxidant supplements do not improve mortality and may cause harm. Am Fam Physician. 2008;78(9):1079-1080.
83. Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis. JAMA. 2007;297(8):842-857. (Pubitemid 46333949)
84. Bjelakovic G, Nikolova D, Simonetti R, Gluud C. Antioxidant supplements for prevention of gastrointestinal cancers: a systematic review and meta-analysis. Lancet. 2004;364(9441):1219-1228. (Pubitemid 39311342)
85. Dai DF, Rabinovitch PS, Ungvari Z. Mitochondria and cardiovascular aging. Circ Res. 2012;110(8):1109-1124.
86. Lambert AJ, et al. Low rates of hydrogen peroxide production by isolated heart mitochondria associate with long maximum lifespan in vertebrate homeotherms. Aging Cell. 2007;6(5):607-618. (Pubitemid 47400043)
87. Cochemé HM, et al. Measurement of H2O2 within living Drosophila during aging using a ratiometric mass spectrometry probe targeted to the mitochondrial matrix. Cell Metab. 2011;13(3):340-350.
88. Andziak B, O'Connor TP, Buffenstein R. Antioxidants do not explain the disparate longevity between mice and the longest-living rodent, the naked molerat. Mech Ageing Dev. 2005;126(11):1206-1212. (Pubitemid 41356522)
89. Andziak B, et al. High oxidative damage levels in the longest-living rodent, the naked mole-rat. Aging Cell. 2006;5(6):463-471. (Pubitemid 44782615)
90. Yang W, Hekimi S. A mitochondrial superoxide signal triggers increased longevity in Caenorhabditis elegans. PloS Biol. 2010;8(12):e1000556.
91. Copeland JM, et al. Extension of Drosophila life span by RNAi of the mitochondrial respiratory chain. Curr Biol. 2009;19(19):1591-1598.
92. Csiszar A, et al. Endothelial function and vascular oxidative stress in long-lived GH/IGF-deficient Ames dwarf mice. Am J Physiol Heart Circ Physiol. 2008; 295(5):H1882-H1894.
93. Zarse K, et al. Impaired insulin/IGF1 signaling extends life span by promoting mitochondrial L-proline catabolism to induce a transient ROS signal. Cell Metab. 2012;15(4):451-465.
94. Hekimi S, Lapointe J, Wen Y. Taking a "good" look at free radicals in the aging process. Trends Cell Biol. 2011;21(10):569-576.
95. Rea SL, Ventura N, Johnson TE. Relationship between mitochondrial electron transport chain dysfunction, development, and life extension in Caenorhabditis elegans. PloS Biol. 2007;5(10):e259.
96. Verbon EH, Post JA, Boonstra J. The influence of reactive oxygen species on cell cycle progression in mammalian cells. Gene. 2012;511(1):1-6.
97. Burhans WC, Heintz NH. The cell cycle is a redox cycle: Linking phase-specific targets to cell fate. Free Radic Biol Med. 2009;47(9):1282-1293.
98. Sohal RS, Orr WC. The redox stress hypothesis of aging. Free Radic Biol Med. 2012;52(3):539-555.
99. Ristow M, et al. Antioxidants prevent health-promoting effects of physical exercise in humans. Proc Natl Acad Sci U S A. 2009;106(21):8665-8670.
100. Ryan MT, Hoogenraad NJ. Mitochondrial-nuclear communications. Annu Rev Biochem. 2007; 76(1):701-722.
101. Holzenberger M, et al. IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice. Nature. 2003;421(6919):182-187. (Pubitemid 36090987)
102. Choi J-S, Choi K-M, Lee C-K. Caloric restriction improves efficiency and capacity of the mitochondrial electron transport chain in Saccharomyces cerevisiae. Biochem Biophys Res Commun. 2011;409(2):308-314.
103. Kapahi P, et al. Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway. Curr Biol. 2004;14(10):885-890. (Pubitemid 38800910)
104. Bonawitz ND, Chatenay-Lapointe M, Pan Y, Shadel GS. Reduced TOR signaling extends chronological life span via increased respiration and upregulation of mitochondrial gene expression. Cell Metab. 2007;5(4):265-277. (Pubitemid 46477854)
105. Powers RW. Extension of chronological life span in yeast by decreased TOR pathway signaling. Genes Dev. 2006;20(2):174-184.
106. Vellai T, et al. Genetics: influence of TOR kinase on lifespan in C. elegans. Nature. 2003;426(6967):620. (Pubitemid 38009359)
107. Kaeberlein M. Regulation of yeast replicative life span by TOR and Sch9 in response to nutrients. Science. 2005;310(5751):1193-1196. (Pubitemid 41681747)
108. Murphy CT, et al. Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans. Nature. 2003;424(6946):277-283.
109. Schulz TJ, Zarse K, Voigt A, Urban N, Birringer M, Ristow M. Glucose restriction extends Caenorhabditis elegans life span by inducing mitochondrial respiration and increasing oxidative stress. Cell Metab. 2007;6(4):280-293. (Pubitemid 47468090)
110. Selman C, et al. Ribosomal protein S6 kinase 1 signaling regulates mammalian life span. Science. 2009;326(5949):140.
111. Weindruch R, Walford RL. The Retardation of Aging and Disease by Dietary Restriction. St. Louis, Missouri, USA: Charles C Thomas Pub Ltd.; 1988.
112. Kaeberlein M, Burtner C. Recent developments in yeast aging. PLoS Genet. 2007;3(5):e84.
113. Colman RJ, et al. Caloric restriction delays disease onset and mortality in rhesus monkeys. Science. 2009;325(5937):201-204.
114. Dai DF, Rabinovitch PS, Ungvari Z. Mitochondria and cardiovascular aging. Circ Res. 2012; 110(8):1109-1124.
115. Cohen HY. Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase. Science. 2004;305(5682):390-392. (Pubitemid 38938153)
116. López-Lluch G, et al. Calorie restriction induces mitochondrial biogenesis and bioenergetic efficiency. Proc Natl Acad Sci U S A. 2006;103(6):1768-1773. (Pubitemid 43228768)
117. Mootha VK, et al. PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet. 2003;34(3):267-273. (Pubitemid 36792858)
118. Anderson RM, et al. Dynamic regulation of PGC- 1α localization and turnover implicates mitochondrial adaptation in calorie restriction and the stress response. Aging Cell. 2008;7(1):101-111.
119. Choi CS, et al. Paradoxical effects of increased expression of PGC-1α on muscle mitochondrial function and insulin-stimulated muscle glucose metabolism. Proc Natl Acad Sci U S A. 2008;105(50):19926-19931.
120. Finley LWS, Haigis MC. The coordination of nuclear and mitochondrial communication during aging and calorie restriction. Ageing Res Rev. 2009;8(3):173-188.
121. Baker DJ, Betik AC, Krause DJ, Hepple RT. No decline in skeletal muscle oxidative capacity with aging in long-term calorically restricted rats: effects are independent of mitochondrial DNA integrity. J Gerontol A Biol Sci Med Sci. 2006;61(7):675-684. (Pubitemid 44148352)
122. Katic M, et al. Mitochondrial gene expression and increased oxidative metabolism: role in increased lifespan of fat-specific insulin receptor knock-out mice. Aging Cell. 2007;6(6):827-839. (Pubitemid 350131051)
123. Rera M, et al. Modulation of longevity and tissue homeostasis by the Drosophila PGC-1 homolog. Cell Metab. 2011;14(5):623-634.
124. Lee C-K, Allison DB, Brand J, Weindruch R, Prolla TA. Transcriptional profiles associated with aging and middle age-onset caloric restriction in mouse hearts. Proc Natl Acad Sci U S A. 2002;99(23):14988-14993. (Pubitemid 35334597)
125. Gwinn DM, et al. AMPK phosphorylation of raptor mediates a metabolic checkpoint. Mol Cell. 2008; 30(2):214-226. (Pubitemid 351626684)