Mitochondria in the spotlight of aging and idiopathic pulmonary fibrosis

Journal of Clinical Investigation

Volumn 127, Issue 2, 2017, Pages 405-414

  Mora, Ana L ^a   Bueno, Marta ^a   Rojas, Mauricio ^a  

^a UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AGING; AUTOPHAGY; CELL AGING; DISORDERS OF MITOCHONDRIAL FUNCTIONS; EPIGENETICS; FIBROSING ALVEOLITIS; GENOMIC INSTABILITY; HUMAN; METABOLIC DISORDER; MITOCHONDRION; PATHOPHYSIOLOGY; PHENOTYPE; PHYSIOLOGY; PRIORITY JOURNAL; PROTEIN HOMEOSTASIS; REVIEW; SENESCENCE ASSOCIATED SECRETORY PHENOTYPE; TELOMERE; ANIMAL; FIBROBLAST; LUNG; METABOLISM; PATHOLOGY; RESPIRATORY MUCOSA;

AGING; ANIMALS; FIBROBLASTS; HUMANS; IDIOPATHIC PULMONARY FIBROSIS; LUNG; MITOCHONDRIA; RESPIRATORY MUCOSA;

EID: 85014069448     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI87440     Document Type: Review

References (162)

1. Bloom DE, Shannon S. The demographic of aging. In: Molecular Aspects of Aging: Understanding Lung Aging. Rojas M, Meiners S, Le Saux CJ, eds. Hoboken, New Jersey, USA: Wiley-Blackwell; 2014:1-12.
2. Ley B, Collard HR. Epidemiology of idiopathic pulmonary fibrosis. Clin Epidemiol. 2013;5(1):483-492.
3. Coultas DB, Zumwalt RE, Black WC, Sobonya RE. The epidemiology of interstitial lung diseases. Am J Respir Crit Care Med. 1994;150(4):967-972.
4. Raghu G, Weycker D, Edelsberg J, Bradford WZ, Oster G. Incidence and prevalence of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2006;174(7):810-816.
5. Fernández Pérez ER, et al. Incidence, prevalence, and clinical course of idiopathic pulmonary fibrosis: A population-based study. Chest. 2010;137(1):129-137.
6. Gribbin J, Hubbard RB, Le Jeune I, Smith CJ, West J, Tata LJ. Incidence and mortality of idiopathic pulmonary fibrosis and sarcoidosis in the UK. Thorax. 2006;61(11):980-985.
7. Natsuizaka M, et al. Epidemiologic survey of Japanese patients with idiopathic pulmonary fibrosis and investigation of ethnic differences. Am J Respir Crit Care Med. 2014;190(7):773-779.
8. Navaratnam V, Fleming KM, West J, Smith CJ, Jenkins RG, et al. The rising incidence of idiopathic pulmonary fibrosis in the U.K. Thorax. 2011;66(6):462-467.
9. Raghu G, Chen SY, Hou Q, Yeh WS, Collard HR. Incidence and prevalence of idiopathic pulmonary fibrosis in US adults 18-64 years old. Eur Respir J. 2016;48(1):179-186.
10. Hutchinson JP, McKeever TM, Fogarty AW, Navaratnam V, Hubbard RB. Increasing global mortality from idiopathic pulmonary fibrosis in the twenty-first century. Ann Am Thorac Soc. 2014;11(8):1176-1185.
11. Collard HR, et al. Health care utilization and costs of idiopathic pulmonary fibrosis in U.S. Medicare beneficiaries aged 65 years and older. Ann Am Thorac Soc. 2015;12(7):981-987.
12. Kirkwood TB, Austad SN. Why do we age? Nature. 2000;408(6809):233-238.
13. Kirkwood TB, Rose MR. Evolution of senescence: late survival sacrificed for reproduction. Philos Trans R Soc Lond B Biol Sci. 1991;332(1262):15-24.
14. Wang L, Green FH, Smiley-Jewell SM, Pinkerton KE. Susceptibility of the aging lung to environmental injury. Semin Respir Crit Care Med. 2010;31(5):539-553.
15. Copley SJ, et al. Lung morphology in the elderly: comparative CT study of subjects over 75 years old versus those under 55 years old. Radiology. 2009;251(2):566-573.
16. Hashimoto M, et al. Elimination of p19(ARF)-expressing cells enhances pulmonary function in mice. JCI Insight. 2016;1(12):e87732.
17. Bueno M, et al. PINK1 deficiency impairs mitochondrial homeostasis and promotes lung fibrosis. J Clin Invest. 2015;125(2):521-538.
18. Braidy N, Guillemin GJ, Mansour H, Chan-Ling T, Poljak A, Grant R. Age related changes in NAD+ metabolism oxidative stress and Sirt1 activity in wistar rats. PLoS One. 2011;6(4):e19194.
19. Sosulski ML, Gongora R, Danchuk S, Dong C, Luo F, Sanchez CG. Deregulation of selective autophagy during aging and pulmonary fibrosis: The role of TGFβ1. Aging Cell. 2015;14(5):774-783.
20. Romero Y, et al. mTORC1 activation decreases autophagy in aging and idiopathic pulmonary fibrosis and contribute to apoptosis resistance in IPF fibroblasts [published online ahead of print August 26, 2016]. Aging Cell. doi:10.1111/acel.12514.
21. Sueblinvong V, et al. Predisposition for disrepair in the aged lung. Am J Med Sci. 2012;344(1):41-51.
22. Torres-González E, et al. Role of endoplasmic reticulum stress in age-related susceptibility to lung fibrosis. Am J Respir Cell Mol Biol. 2012;46(6):748-756.
23. Hecker L, et al. Reversal of persistent fibrosis in aging by targeting Nox4-Nrf2 redox imbalance. Sci Transl Med. 2014;6(231):231ra47.
24. Bustos ML, et al. Aging mesenchymal stem cells fail to protect because of impaired migration and antiinflammatory response. Am J Respir Crit Care Med. 2014;189(7):787-798.
25. Lopez-Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell. 2013;153(6):1194-1217.
26. Neri S, et al. Mismatch repair system and aging: microsatellite instability in peripheral blood cells from differently aged participants. J Gerontol A Biol Sci Med Sci. 2005;60(3):285-292.
27. Fingerlin TE, et al. Genome-wide association study identifies multiple susceptibility loci for pulmonary fibrosis. Nat Genet. 2013;45(6):613-620.
28. Mathai SK, Schwartz DA, Warg LA. Genetic susceptibility and pulmonary fibrosis. Curr Opin Pulm Med. 2014;20(5):429-435.
29. Vassilakis DA, Sourvinos G, Spandidos DA, Siafakas NM, Bouros D. Frequent genetic alterations at the microsatellite level in cytologic sputum samples of patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2000;162(3 pt 1):1115-1119.
30. Demopoulos K, Arvanitis DA, Vassilakis DA, Siafakas NM, Spandidos DA. MYCL1, FHIT, SPARC, p16(INK4) and TP53 genes associated to lung cancer in idiopathic pulmonary fibrosis. J Cell Mol Med. 2002;6(2):215-222.
31. Mori M, et al. Microsatellite instability in transforming growth factor-β1 type II receptor gene in alveolar lining epithelial cells of idiopathic pulmonary fibrosis. Am J Respir Cell Mol Biol. 2001;24(4):398-404.
32. Korfei M, et al. Comparative proteomic analysis of lung tissue from patients with idiopathic pulmonary fibrosis (IPF) and lung transplant donor lungs. J Proteome Res. 2011;10(5):2185-2205.
33. Bell JT, et al. Epigenome-wide scans identify differentially methylated regions for age and age-related phenotypes in a healthy ageing population. PLoS Genet. 2012;8(4):e1002629.
34. Tsai PC, Spector TD, Bell JT. Using epigenome-wide association scans of DNA methylation in age-related complex human traits. Epigenomics. 2012;4(5):511-526.
35. Kreiling JA, et al. Age-associated increase in heterochromatic marks in murine and primate tissues. Aging Cell. 2011;10(2):292-304.
36. Spiers H, Hannon E, Wells S, Williams B, Fernandes C, Mill J. Age-associated changes in DNA methylation across multiple tissues in an inbred mouse model. Mech Ageing Dev. 2016;154:20-23.
37. Christensen BC, et al. Aging and environmental exposures alter tissue-specific DNA methylation dependent upon CpG island context. PLoS Genet. 2009;5(8):e1000602.
38. Yang IV, et al. Relationship of DNA methylation and gene expression in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2014;190(11):1263-1272.
39. Gonzalo S. Epigenetic alterations in aging. J Appl Physiol (1985). 2010;109(2):586-597.
40. Vaquero A, Scher M, Lee D, Erdjument-Bromage H, Tempst P, Reinberg D. Human SirT1 interacts with histone H1 and promotes formation of facultative heterochromatin. Mol Cell. 2004;16(1):93-105.
41. Hayakawa T, et al. SIRT1 suppresses the senescence-associated secretory phenotype through epigenetic gene regulation. PLoS One. 2015;10(1):e0116480.
42. Sanders YY, Hagood JS, Liu H, Zhang W, Ambalavanan N, Thannickal VJ. Histone deacetylase inhibition promotes fibroblast apoptosis and ameliorates pulmonary fibrosis in mice. Eur Respir J. 2014;43(5):1448-1458.
43. Abdelmohsen K, Gorospe M. Noncoding RNA control of cellular senescence. Wiley Interdiscip Rev RNA. 2015;6(6):615-629.
44. Pandit KV, Milosevic J, Kaminski N. MicroRNAs in idiopathic pulmonary fibrosis. Transl Res. 2011;157(4):191-199.
45. Pandit KV, et al. Inhibition and role of let-7d in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2010;182(2):220-229.
46. Disayabutr S, et al. miR-34 miRNAs regulate cellular senescence in type II alveolar epithelial cells of patients with idiopathic pulmonary fibrosis. PLoS One. 2016;11(6):e0158367.
47. Selman M, López-Otín C, Pardo A. Age-driven developmental drift in the pathogenesis of idiopathic pulmonary fibrosis. Eur Respir J. 2016;48(2):538-552.
48. Ulitsky I, Bartel DP. lincRNAs: genomics, evolution, and mechanisms. Cell. 2013;154(1):26-46.
49. Grammatikakis I, Panda AC, Abdelmohsen K, Gorospe M. Long noncoding RNAs(lncRNAs) and the molecular hallmarks of aging. Aging (Albany NY). 2014;6(12):992-1009.
50. Huang C, Yang Y, Liu L. Interaction of long noncoding RNAs and microRNAs in the pathogenesis of idiopathic pulmonary fibrosis. Physiol Genomics. 2015;47(10):463-469.
51. Song X, et al. Analysing the relationship between lncRNA and protein-coding gene and the role of lncRNA as ceRNA in pulmonary fibrosis. J Cell Mol Med. 2014;18(6):991-1003.
52. Armanios MY, et al. Telomerase mutations in families with idiopathic pulmonary fibrosis. N Engl J Med. 2007;356(13):1317-1326.
53. Lawson WE, et al. Genetic mutations in surfactant protein C are a rare cause of sporadic cases of IPF. Thorax. 2004;59(11):977-980.
54. Armanios M. Telomerase and idiopathic pulmonary fibrosis. Mutat Res. 2012;730(1-2):52-58.
55. Alder JK, et al. Short telomeres are a risk factor for idiopathic pulmonary fibrosis. Proc Natl Acad Sci U S A. 2008;105(35):13051-13056.
56. Cronkhite JT, Xing C, Raghu G, Chin KM, Torres F, et al. Telomere shortening in familial and sporadic pulmonary fibrosis. Am J Respir Crit Care Med. 2008;178(7):729-737.
57. Diaz de Leon A, et al. Telomere lengths, pulmonary fibrosis and telomerase (TERT) mutations. PLoS One. 2010;5(5):e10680.
58. Diaz de Leon A, et al. Subclinical lung disease, macrocytosis, and premature graying in kindreds with telomerase (TERT) mutations. Chest. 2011;140(3):753-763.
59. Kannengiesser C, et al. Heterozygous RTEL1 mutations are associated with familial pulmonary fibrosis. Eur Respir J. 2015;46(2):474-485.
60. Silhan LL, et al. Lung transplantation in telomerase mutation carriers with pulmonary fibrosis. Eur Respir J. 2014;44(1):178-187.
61. Stuart BD, et al. Exome sequencing links mutations in PARN and RTEL1 with familial pulmonary fibrosis and telomere shortening. Nat Genet. 2015;47(5):512-517.
62. Tsakiri KD, et al. Adult-onset pulmonary fibrosis caused by mutations in telomerase. Proc Natl Acad Sci U S A. 2007;104(18):7552-7557.
63. Tsang AR, Wyatt HD, Ting NS, Beattie TL. hTERT mutations associated with idiopathic pulmonary fibrosis affect telomerase activity, telomere length, and cell growth by distinct mechanisms. Aging Cell. 2012;11(3):482-490.
64. Alder JK, et al. Telomere dysfunction causes alveolar stem cell failure. Proc Natl Acad Sci U S A. 2015;112(16):5099-5104.
65. Povedano JM, Martinez P, Flores JM, Mulero F, Blasco MA. Mice with pulmonary fibrosis driven by telomere dysfunction. Cell Rep. 2015;12(2):286-299.
66. Liu T, Ullenbruch M, Young Choi Y, Yu H, Ding L, et al. Telomerase and telomere length in pulmonary fibrosis. Am J Respir Cell Mol Biol. 2013;49(2):260-268.
67. Cusanelli E, Chartrand P. Telomeric repeatcontaining RNA TERRA: A noncoding RNA connecting telomere biology to genome integrity. Front Genet. 2015;6:143.
68. Xu J, et al. Use of senescence-accelerated mouse model in bleomycin-induced lung injury suggests that bone marrow-derived cells can alter the outcome of lung injury in aged mice. J Gerontol A Biol Sci Med Sci. 2009;64(7):731-739.
69. Chen R, et al. Telomerase deficiency causes alveolar stem cell senescence-associated low-grade inflammation in lungs. J Biol Chem. 2015;290(52):30813-30829.
70. Lin C, et al. Protease activated receptor-1 regulates macrophage-mediated cellular senescence: A risk for idiopathic pulmonary fibrosis. Oncotarget. 2015;6(34):35304-35314.
71. Yanai H, et al. Cellular senescence-like features of lung fibroblasts derived from idiopathic pulmonary fibrosis patients. Aging (Albany NY). 2015;7(9):664-672.
72. Sanders YY, Liu H, Liu G, Thannickal VJ. Epigenetic mechanisms regulate NADPH oxidase-4 expression in cellular senescence. Free Radic Biol Med. 2015;79:197-205.
73. Orjalo AV, Bhaumik D, Gengler BK, Scott GK, Campisi J. Cell surface-bound IL-1α is an upstream regulator of the senescence-associated IL-6/IL-8 cytokine network. Proc Natl Acad Sci U S A. 2009;106(40):17031-17036.
74. Maciel-Barón LA, et al. Senescence associated secretory phenotype profile from primary lung mice fibroblasts depends on the senescence induction stimuli. Age (Dordr). 2016;38(1):26.
75. Stout-Delgado HW, et al. Age-dependent susceptibility to pulmonary fibrosis is associated with NLRP3 inflammasome activation. Am J Respir Cell Mol Biol. 2016;55(2):252-263.
76. Powter EE, et al. Caveolae control the antiinflammatory phenotype of senescent endothelial cells. Aging Cell. 2015;14(1):102-111.
77. Shivshankar P, Brampton C, Miyasato S, Kasper M, Thannickal VJ, Le Saux CJ. Caveolin-1 deficiency protects from pulmonary fibrosis by modulating epithelial cell senescence in mice. Am J Respir Cell Mol Biol. 2012;47(1):28-36.
78. Minagawa S, et al. Accelerated epithelial cell senescence in IPF and the inhibitory role of SIRT6 in TGF-β-induced senescence of human bronchial epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2011;300(3):L391-L401.
79. Bratic A, Larsson NG. The role of mitochondria in aging. J Clin Invest. 2013;123(3):951-957.
80. Herbener GH. A morphometric study of age-dependent changes in mitochondrial population of mouse liver and heart. J Gerontol. 1976;31(1):8-12.
81. 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.
82. Herbst A, Pak JW, McKenzie D, Bua E, Bassiouni M, Aiken JM. Accumulation of mitochondrial DNA deletion mutations in aged muscle fibers: evidence for a causal role in muscle fiber loss. J Gerontol A Biol Sci Med Sci. 2007;62(3):235-245.
83. Wallace DC. Mitochondrial DNA mutations in disease and aging. Environ Mol Mutagen. 2010;51(5):440-450.
84. Hawkins A, et al. A non-BRICHOS SFTPC mutant (SP-CI73T) linked to interstitial lung disease promotes a late block in macroautophagy disrupting cellular proteostasis and mitophagy. Am J Physiol Lung Cell Mol Physiol. 2015;308(1):L33-L47.
85. Patel AS, et al. Epithelial cell mitochondrial dysfunction and PINK1 are induced by transforming growth factor-beta1 in pulmonary fibrosis. PLoS One. 2015;10(3):e0121246.
86. Kobayashi K, et al. Involvement of PARK2-mediated mitophagy in idiopathic pulmonary fibrosis pathogenesis. J Immunol. 2016;197(2):504-516.
87. Sundaresan NR, et al. SIRT3 blocks agingassociated tissue fibrosis in mice by deacetylating and activating glycogen synthase kinase 3β. Mol Cell Biol. 2015;36(5):678-692.
88. Sosulski ML, Gongora R, Feghali-Bostwick C, Lasky JA, Sanchez CG. Sirtuin 3 deregulation promotes pulmonary fibrosis. J Gerontol A Biol Sci Med Sci. doi:10.1093/gerona/glw151.
89. Kim SJ, Cheresh P, Jablonski RP, Williams DB, Kamp DW. The role of mitochondrial DNA in mediating alveolar epithelial cell apoptosis and pulmonary fibrosis. Int J Mol Sci. 2015;16(9):21486-21519.
90. Akamata K, et al. SIRT3 is attenuated in systemic sclerosis skin and lungs, and its pharmacologic activation mitigates organ fibrosis [published online ahead of print October 6, 2016]. Oncotarget. doi: 10.18632/oncotarget.12504.
91. Cheng Y, et al. Interaction of Sirt3 with OGG1 contributes to repair of mitochondrial DNA and protects from apoptotic cell death under oxidative stress. Cell Death Dis. 2013;4:e731.
92. Kim SJ, et al. Mitochondria-targeted Ogg1 and aconitase-2 prevent oxidant-induced mitochondrial DNA damage in alveolar epithelial cells. J Biol Chem. 2014;289(9):6165-6176.
93. Cheresh P, et al. Asbestos-induced pulmonary fibrosis is augmented in 8-oxoguanine DNA glycosylase knockout mice. Am J Respir Cell Mol Biol. 2015;52(1):25-36.
94. Panduri V, et al. Role of mitochondrial hOGG1 and aconitase in oxidant-induced lung epithelial cell apoptosis. Free Radic Biol Med. 2009;47(6):750-759.
95. Fahn HJ, et al. Age-related 4,977 bp deletion in human lung mitochondrial DNA. Am J Respir Crit Care Med. 1996;154(4 pt 1):1141-1145.
96. Lee HC, Lu CY, Fahn HJ, Wei YH. Aging-and smoking-associated alteration in the relative content of mitochondrial DNA in human lung. FEBS Lett. 1998;441(2):292-296.
97. Kwon Y, Kim J, Lee CY, Kim H. Expression of SIRT1 and SIRT3 varies according to age in mice. Anat Cell Biol. 2015;48(1):54-61.
98. Trifunovic A, et al. Premature ageing in mice expressing defective mitochondrial DNA polymerase. Nature. 2004;429(6990):417-423.
99. Kropski JA, et al. Extensive phenotyping of individuals at risk for familial interstitial pneumonia reveals clues to the pathogenesis of interstitial lung disease. Am J Respir Crit Care Med. 2015;191(4):417-426.
100. Lawson WE, et al. Endoplasmic reticulum stress enhances fibrotic remodeling in the lungs. Proc Natl Acad Sci U S A. 2011;108(26):10562-10567.
101. Tanjore H, Lawson WE, Blackwell TS. Endoplasmic reticulum stress as a pro-fibrotic stimulus. Biochim Biophys Acta. 2013;1832(7):940-947.
102. Yao Y, et al. Chop deficiency protects mice against bleomycin-induced pulmonary fibrosis by attenuating M2 macrophage production. Mol Ther. 2016;24(5):915-925.
103. Baker TA, Bach HH, Gamelli RL, Love RB, Majetschak M. Proteasomes in lungs from organ donors and patients with end-stage pulmonary diseases. Physiol Res. 2014;63(3):311-319.
104. Semren N, et al. Regulation of 26S Proteasome Activity in Pulmonary Fibrosis. Am J Respir Crit Care Med. 2015;192(9):1089-1101.
105. Maitra M, Wang Y, Gerard RD, Mendelson CR, Garcia CK. Surfactant protein A2 mutations associated with pulmonary fibrosis lead to protein instability and endoplasmic reticulum stress. J Biol Chem. 2010;285(29):22103-22113.
106. Nogee LM, Dunbar AE, Wert SE, Askin F, Hamvas A, Whitsett JA. A mutation in the surfactant protein C gene associated with familial interstitial lung disease. N Engl J Med. 2001;344(8):573-579.
107. Thomas AQ, et al. Heterozygosity for a surfactant protein C gene mutation associated with usual interstitial pneumonitis and cellular nonspecific interstitial pneumonitis in one kindred. Am J Respir Crit Care Med. 2002;165(9):1322-1328.
108. Wang Y, et al. Genetic defects in surfactant protein A2 are associated with pulmonary fibrosis and lung cancer. Am J Hum Genet. 2009;84(1):52-59.
109. Peljto AL, et al. Association between the MUC5B promoter polymorphism and survival in patients with idiopathic pulmonary fibrosis. JAMA. 2013;309(21):2232-2239.
110. Korfei M, et al. Epithelial endoplasmic reticulum stress and apoptosis in sporadic idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2008;178(8):838-846.
111. Lawson WE, et al. Endoplasmic reticulum stress in alveolar epithelial cells is prominent in IPF: association with altered surfactant protein processing and herpesvirus infection. Am J Physiol Lung Cell Mol Physiol. 2008;294(6):L1119-L1126.
112. Jorgensen E, Stinson A, Shan L, Yang J, Gietl D, Albino AP. Cigarette smoke induces endoplasmic reticulum stress and the unfolded protein response in normal and malignant human lung cells. BMC Cancer. 2008;8:229.
113. Lee DY, Sugden B. The LMP1 oncogene of EBV activates PERK and the unfolded protein response to drive its own synthesis. Blood. 2008;111(4):2280-2289.
114. He C, Klionsky DJ. Regulation mechanisms and signaling pathways of autophagy. Annu Rev Genet. 2009;43:67-93.
115. Araya J, et al. Insufficient autophagy in idiopathic pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol. 2013;304(1):L56-L69.
116. Nho RS, Hergert P. IPF fibroblasts are desensitized to type I collagen matrix-induced cell death by suppressing low autophagy via aberrant Akt/mTOR kinases. PLoS One. 2014;9(4):e94616.
117. Patel AS, et al. Autophagy in idiopathic pulmonary fibrosis. PLoS One. 2012;7(7):e41394.
118. Ricci A, et al. Decreased expression of autophagic beclin 1 protein in idiopathic pulmonary fibrosis fibroblasts. J Cell Physiol. 2013;228(7):1516-1524.
119. Im J, Hergert P, Nho RS. Reduced FoxO3a expression causes low autophagy in idiopathic pulmonary fibrosis fibroblasts on collagen matrices. Am J Physiol Lung Cell Mol Physiol. 2015;309(6):L552-L561.
120. Huang LS, et al. Sphingosine-1-phosphate lyase is an endogenous suppressor of pulmonary fibrosis: role of S1P signalling and autophagy. Thorax. 2015;70(12):1138-1148.
121. Cabrera S, et al. Essential role for the ATG4B protease and autophagy in bleomycin-induced pulmonary fibrosis. Autophagy. 2015;11(4):670-684.
122. Huang SX, Jaurand MC, Kamp DW, Whysner J, Hei TK. Role of mutagenicity in asbestos fiber-induced carcinogenicity and other diseases. J Toxicol Environ Health B Crit Rev. 2011;14(1-4):179-245.
123. Kamp DW, Panduri Va, Weitzman SA, Chandel N. Asbestos-induced alveolar epithelial cell apoptosis: role of mitochondrial dysfunction caused by iron-derived free radicals. Mol Cell Biochem. 2002;234-235(1-2):153-160.
124. Fang EF, Scheibye-Knudsen M, Chua KF, Mattson MP, Croteau DL, Bohr VA. Nuclear DNA damage signalling to mitochondria in ageing. Nat Rev Mol Cell Biol. 2016;17(5):308-321.
125. Fang EF, et al. Defective mitophagy in XPA via PARP-1 hyperactivation and NAD(+)/SIRT1 reduction. Cell. 2014;157(4):882-896.
126. Rodgers JT, Lerin C, Haas W, Gygi SP, Spiegelman BM, Puigserver P. Nutrient control of glucose homeostasis through a complex of PGC-1α and SIRT1. Nature. 2005;434(7029):113-118.
127. Toiber D, et al. SIRT6 recruits SNF2H to DNA break sites, preventing genomic instability through chromatin remodeling. Mol Cell. 2013;51(4):454-468.
128. Hu B, Wu Z, Hergert P, Henke CA, Bitterman PB, Phan SH. Regulation of myofibroblast differentiation by poly(ADP-ribose) polymerase 1. Am J Pathol. 2013;182(1):71-83.
129. Smiraglia DJ, Kulawiec M, Bistulfi GL, Gupta SG, Singh KK. A novel role for mitochondria in regulating epigenetic modification in the nucleus. Cancer Biol Ther. 2008;7(8):1182-1190.
130. Bellizzi D, D'Aquila P, Giordano M, Montesanto A, Passarino G. Global DNA methylation levels are modulated by mitochondrial DNA variants. Epigenomics. 2012;4(1):17-27.
131. Hitchler MJ, Domann FE. An epigenetic perspective on the free radical theory of development. Free Radic Biol Med. 2007;43(7):1023-1036.
132. Kren BT, Wong PY, Sarver A, Zhang X, Zeng Y, Steer CJ. MicroRNAs identified in highly purified liver-derived mitochondria may play a role in apoptosis. RNA Biol. 2009;6(1):65-72.
133. Rebelo AP, Williams SL, Moraes CT. In vivo methylation of mtDNA reveals the dynamics of protein-mtDNA interactions. Nucleic Acids Res. 2009;37(20):6701-6715.
134. Shock LS, Thakkar PV, Peterson EJ, Moran RG, Taylor SM. DNA methyltransferase 1, cytosine methylation, and cytosine hydroxymethylation in mammalian mitochondria. Proc Natl Acad Sci U S A. 2011;108(9):3630-3635.
135. Sripada L, Tomar D, Prajapati P, Singh R, Singh AK, Singh R. Systematic analysis of small RNAs associated with human mitochondria by deep sequencing: detailed analysis of mitochondrial associated miRNA. PLoS One. 2012;7(9):e44873.
136. Wallace DC, Fan W. Energetics, epigenetics, mitochondrial genetics. Mitochondrion. 2010;10(1):12-31.
137. Shmookler Reis RJ, Goldstein S. Mitochondrial DNA in mortal and immortal human cells. Genome number, integrity, and methylation. J Biol Chem. 1983;258(15):9078-9085.
138. Sahin E, et al. Telomere dysfunction induces metabolic and mitochondrial compromise. Nature. 2011;470(7334):359-365.
139. Liu L, Trimarchi JR, Smith PJ, Keefe DL. Mitochondrial dysfunction leads to telomere attrition and genomic instability. Aging Cell. 2002;1(1):40-46.
140. Wiley CD, et al. Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype. Cell Metab. 2016;23(2):303-314.
141. Jiang P, Du W, Mancuso A, Wellen KE, Yang X. Reciprocal regulation of p53 and malic enzymes modulates metabolism and senescence. Nature. 2013;493(7434):689-693.
142. Lee SM, Dho SH, Ju SK, Maeng JS, Kim JY, Kwon KS. Cytosolic malate dehydrogenase regulates senescence in human fibroblasts. Biogerontology. 2012;13(5):525-536.
143. Passos JF, et al. Feedback between p21 and reactive oxygen production is necessary for cell senescence. Mol Syst Biol. 2010;6:347.
144. Ziegler DV, Wiley CD, Velarde MC. Mitochondrial effectors of cellular senescence: beyond the free radical theory of aging. Aging Cell. 2015;14(1):1-7.
145. Houtkooper RH, et al. Mitonuclear protein imbalance as a conserved longevity mechanism. Nature. 2013;497(7450):451-457.
146. Quirós PM, Langer T, López-Otín C. New roles for mitochondrial proteases in health, ageing and disease. Nat Rev Mol Cell Biol. 2015;16(6):345-359.
147. Quirós PM, Ramsay AJ, López-Otín C. New roles for OMA1 metalloprotease: From mitochondrial proteostasis to metabolic homeostasis. Adipocyte. 2013;2(1):7-11.
148. Johnson TE. 25 years after age-1: genes, interventions and the revolution in aging research. Exp Gerontol. 2013;48(7):640-643.
149. Kenyon CJ. The genetics of ageing. Nature. 2010;464(7288):504-512.
150. Longo VD, et al. Interventions to Slow Aging in Humans: Are We Ready? Aging Cell. 2015;14(4):497-510.
151. Longo VD, Mattson MP. Fasting: molecular mechanisms and clinical applications. Cell Metab. 2014;19(2):181-192.
152. Masoro EJ, Shimokawa I, Higami Y, McMahan CA, Yu BP. Temporal pattern of food intake not a factor in the retardation of aging processes by dietary restriction. J Gerontol A Biol Sci Med Sci. 1995;50A(1):B48-B53.
153. Mattson MP, et al. Meal frequency and timing in health and disease. Proc Natl Acad Sci U S A. 2014;111(47):16647-16653.
154. Morgan TE, Wong AM, Finch CE. Antiinflammatory mechanisms of dietary restriction in slowing aging processes. Interdiscip Top Gerontol. 2007;35:83-97.
155. Zhu Y, et al. The Achilles' heel of senescent cells: from transcriptome to senolytic drugs. Aging Cell. 2015;14(4):644-658.
156. Viscomi C, Bottani E, Zeviani M. Emerging concepts in the therapy of mitochondrial disease. Biochim Biophys Acta. 2015;1847(6-7):544-557.
157. Viscomi C, et al. In vivo correction of COX deficiency by activation of the AMPK/PGC-1alpha axis. Cell Metab. 2011;14(1):80-90.
158. Johri A, et al. Pharmacologic activation of mitochondrial biogenesis exerts widespread beneficial effects in a transgenic mouse model of Huntington's disease. Hum Mol Genet. 2012;21(5):1124-1137.
159. Kim SJ, et al. Mitochondrial catalase overexpressed transgenic mice are protected against lung fibrosis in part via preventing alveolar epithelial cell mitochondrial DNA damage. Free Radic Biol Med. 2016;101:482-490.
160. Mizumura K, et al. Mitophagy-dependent necroptosis contributes to the pathogenesis of COPD. J Clin Invest. 2014;124(9):3987-4003.
161. Suen DF, Narendra DP, Tanaka A, Manfredi G, Youle RJ. Parkin overexpression selects against a deleterious mtDNA mutation in heteroplasmic cybrid cells. Proc Natl Acad Sci U S A. 2010;107(26):11835-11840.
162. Konopka AR, Suer MK, Wolff CA, Harber MP. Markers of human skeletal muscle mitochondrial biogenesis and quality control: effects of age and aerobic exercise training. J Gerontol A Biol Sci Med Sci. 2014;69(4):371-378.