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Aging and IPF: What Is the Link?

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Idiopathic Pulmonary Fibrosis

Part of the book series: Respiratory Medicine ((RM,volume 9))

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Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive and usually lethal interstitial lung disease of unknown etiology that is characterized by epithelial cell injury and aberrant activation, expansion of the mesenchymal cell population with the formation of fibroblast/myofibroblast foci, and exaggerated extracellular matrix accumulation. IPF is an aging-related disease, and most patients are over 60 years of age at the time of clinical presentation and diagnosis. Age also influences mortality, and the median survival time is significantly shorter in older individuals compared with younger patients. However, the fundamental mechanisms linking aging to IPF remain unclear. In this chapter, we will discuss some of the modifications naturally occurring in the elderly that may be implicated in the pathogenesis of IPF, including endoplasmic reticulum stress, oxidative stress, mitochondrial dysfunction, dysregulated autophagy, telomere attrition, and a number of epigenetic changes.

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References

  1. Heemels MT. Ageing. Nature. 2010;464:503.

    PubMed  CAS  Google Scholar 

  2. Berdasco M, Esteller M. Hot topics in epigenetic mechanisms of aging: 2011. Aging Cell. 2012;11:181–6.

    PubMed  CAS  Google Scholar 

  3. Rando TA, Chang HY. Aging, rejuvenation, and epigenetic reprogramming: resetting the aging clock. Cell. 2012;148:46–57.

    PubMed  CAS  Google Scholar 

  4. Lister R, Ecker JR. Finding the fifth base: genome-wide sequencing of cytosine methylation. Genome Res. 2009;19:959–66.

    PubMed  CAS  Google Scholar 

  5. Weber M, Hellmann I, Stadler MB, Ramos L, Pääbo S, Rebhan M, et al. Distribution, silencing potential and evolutionary impact of promoter DNA methylation in the human genome. Nat Genet. 2007;39:457–66.

    PubMed  CAS  Google Scholar 

  6. Irizarry RA, Ladd-Acosta C, Wen B, Wu Z, Montano C, Onyango P, et al. The human colon cancer methylome shows similar hypo- and hypermethylation at conserved tissue-specific CpG island shores. Nat Genet. 2009;41:178–86.

    PubMed  CAS  Google Scholar 

  7. Bjornsson HT, Sigurdsson MI, Fallin MD, Irizarry RA, Aspelund T, Cui H, et al. Intra-individual change over time in DNA methylation with familial clustering. JAMA. 2008;299:2877–83.

    PubMed  CAS  Google Scholar 

  8. So K, Tamura G, Honda T, Homma N, Waki T, Togawa N, et al. Multiple tumor suppressor genes are increasingly methylated with age in non-neoplastic gastric epithelia. Cancer Sci. 2006;97:1155–58.

    PubMed  CAS  Google Scholar 

  9. Hernandez DG, Nalls MA, Gibbs JR, Arepalli S, van der Brug M, Chong S, et al. Distinct DNA methylation changes highly correlated with chronological age in the human brain. Hum Mol Genet. 2011;20:1164–72.

    PubMed  CAS  Google Scholar 

  10. Portela A, Esteller M. Epigenetic modifications and human disease. Nat Biotechnol. 2010;28:1057–68.

    PubMed  CAS  Google Scholar 

  11. Lachner M, Jenuwein T. The many faces of histone lysine methylation. Curr Opin Cell Biol. 2002;14:286–98.

    PubMed  CAS  Google Scholar 

  12. Shumaker DK, Dechat T, Kohlmaier A, Adam SA, Bozovsky MR, Erdos MR, et al. Mutant nuclear lamin A leads to progressive alterations of epigenetic control in premature aging. Proc Natl Acad Sci USA. 2006;103:8703–8.

    PubMed  CAS  Google Scholar 

  13. Krishnan V, Chow MZ, Wang Z, Zhang L, Liu B, Liu X, et al. Histone H4 lysine 16 hypoacetylation is associated with defective DNA repair and premature senescence in Zmpste24-deficient mice. Proc Natl Acad Sci USA. 2011;108:12325–30.

    PubMed  CAS  Google Scholar 

  14. Wang GG, Allis CD, Chi P. Chromatin remodeling and cancer, Part II: ATP dependent chromatin remodeling. Trends Mol Med. 2007;13:373–80.

    PubMed  Google Scholar 

  15. Villeponteau B. The heterochromatin loss model of aging. Exp Gerontol. 1997;32:383–94.

    PubMed  CAS  Google Scholar 

  16. Koch CM, Suschek CV, Lin Q, Bork S, Goergens M, Joussen S, et al. Specific age-associated DNA methylation changes in human dermal fibroblasts. PLoS One. 2011;6(2):e16679.

    PubMed  CAS  Google Scholar 

  17. Fraga MF, Esteller M. Epigenetics and aging: the targets and the marks. Trends Genet. 2007;23:413–18.

    PubMed  CAS  Google Scholar 

  18. Zaratiegui M, Irvine DV, Martienssen RA. Noncoding RNAs and gene silencing. Cell. 2007;128:763–76.

    PubMed  CAS  Google Scholar 

  19. Guttman M, Rinn JL. Modular regulatory principles of large non-coding RNAs. Nature. 2012;482:339–46.

    PubMed  CAS  Google Scholar 

  20. Krol J, Krol J, Loedige I, Filipowicz W. The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet. 2010;11:597–610.

    PubMed  CAS  Google Scholar 

  21. Smith-Vikos T, Slack FJ. MicroRNAs and their roles in aging. J Cell Sci. 2012;125(Pt 1):7–17.

    PubMed  CAS  Google Scholar 

  22. Bonifacio LN, Jarstfer MB. MiRNA profile associated with replicative senescence, extended cell culture, and ectopic telomerase expression in human foreskin fibroblasts. PLoS One. 2010;5(9):e12519.

    PubMed  Google Scholar 

  23. Gorospe M, Abdelmohsen K. MicroRegulators come of age in senescence. Trends Genet. 2011;27:233–41.

    PubMed  CAS  Google Scholar 

  24. Lee HC, Wei YH. Mitochondria and aging. Adv Exp Med Biol. 2012;942:311–27.

    PubMed  CAS  Google Scholar 

  25. Hara T, Nakamura K, Matsui M, Yamamoto A, Nakahara Y, Suzuki-Migishima R, et al. Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature. 2006;441:885–9.

    PubMed  CAS  Google Scholar 

  26. Cuervo AM, Dice JF. Age-related decline in chaperone-mediated autophagy. J Biol Chem. 2000;275:31505–13.

    PubMed  CAS  Google Scholar 

  27. Martinez-Vicente M, Sovak G, Cuervo AM. Protein degradation and aging. Exp Gerontol. 2005;40:622–33.

    PubMed  CAS  Google Scholar 

  28. Kim I, Rodriguez-Enriquez S, Lemasters JJ. Selective degradation of mitochondria by mitophagy. Arch Biochem Biophys. 2007;462:245–53.

    PubMed  CAS  Google Scholar 

  29. Woehlbier U, Hetz C. Modulating stress responses by the UPRosome: a matter of life and death. Trends Biochem Sci. 2011;36:329–37.

    PubMed  CAS  Google Scholar 

  30. Cuervo AM. Autophagy and aging: keeping that old broom working. Trends Genet. 2008;24:604–12.

    PubMed  CAS  Google Scholar 

  31. Harley CB, Futcher AB, Greider CW. Telomeres shorten during ageing of human fibroblasts. Nature. 1990;345:458–60.

    PubMed  CAS  Google Scholar 

  32. Kuilman T, Michaloglou C, Mooi WJ, Peeper DS. The essence of senescence. Genes Dev. 2010;24:2463–79.

    PubMed  CAS  Google Scholar 

  33. Londoño-Vallejo JA, Wellinger RJ. Telomeres and telomerase dance to the rhythm of the cell cycle. Trends Biochem Sci. 2012;37(9):391–9.

    PubMed  Google Scholar 

  34. Vera E, Blasco MA. Beyond average: potential for measurement of short telomeres. Aging (Albany NY). 2012;4:379–92.

    CAS  Google Scholar 

  35. Janssens JP, Pache JC, Nicod LP. Physiological changes in respiratory function associated with ageing. Eur Respir J. 1999;13:197–205.

    PubMed  CAS  Google Scholar 

  36. Meyer KC. Aging. Proc Am Thorac Soc. 2005;2:433–9.

    PubMed  CAS  Google Scholar 

  37. Reddy GK. AGE-related cross-linking of collagen is associated with aortic wall matrix stiffness in the pathogenesis of drug-induced diabetes in rats. Microvasc Res. 2004;68:132–42.

    PubMed  Google Scholar 

  38. DeGroot J, Verzijl N, Budde M, Bijlsma JW, Lafeber FP, TeKoppele JM. Accumulation of advanced glycation end products decreases collagen turnover by bovine chondrocytes. Exp Cell Res. 2001;266:303–10.

    PubMed  CAS  Google Scholar 

  39. Rolewska P, Al-Robaiy S, Navarrete Santos A, Simm A, Silber RE, Bartling B. Age-related expression, enzymatic solubility and modification with advanced glycation end-products of fibrillar collagens in mouse lung. Exp Gerontol. 2013;48:29–37.

    Google Scholar 

  40. Calabresi C, Arosio B, Galimberti L, Scanziani E, Bergottini R, Annoni G, et al. Natural aging, expression of fibrosis-related genes and collagen deposition in rat lung. Exp Gerontol. 2007;42:1003–11.

    PubMed  CAS  Google Scholar 

  41. Huang K, Rabold R, Schofield B, Mitzner W, Tankersley CG. Age-dependent changes of airway and lung parenchyma in C57BL/6J mice. J Appl Physiol. 2007;102:200–6.

    PubMed  Google Scholar 

  42. Paxson JA, Gruntman A, Parkin CD, Mazan MR, Davis A, Ingenito EP, et al. Age-dependent decline in mouse lung regeneration with loss of lung fibroblast clonogenicity and increased myofibroblastic differentiation. PLoS One. 2012;6:e23232.

    Google Scholar 

  43. Takubo Y, Hirai T, Muro S, Kogishi K, Hosokawa M, Mishima M. Age-associated changes in elastin and collagen content and the proportion of types I and III collagen in the lungs of mice. Exp Gerontol. 1999;34:353–64.

    PubMed  CAS  Google Scholar 

  44. Sherratt MJ. Tissue elasticity and the ageing elastic fibre. Age (Dordr). 2009;31:305–25.

    CAS  Google Scholar 

  45. Konova E, Baydanoff S, Atanasova M, Velkova A. Age-related changes in the glycation of human aortic elastin. Exp Gerontol. 2004;39:249–54.

    PubMed  CAS  Google Scholar 

  46. Franceschi C, Capri M, Monti D, Giunta S, Olivieri F, Sevini F, et al. Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mech Ageing Dev. 2007;128:92–105.

    PubMed  CAS  Google Scholar 

  47. Ito K. Does lung aging have an impact on chronic obstructive pulmonary disease? J Organ Dysfunction. 2007;3:204–20.

    Google Scholar 

  48. Pawelec G, Larbi A. Immunity and ageing in man: annual review 2006/2007. Exp Gerontol. 2008;43:34–8.

    PubMed  CAS  Google Scholar 

  49. Lee N, Shin MS, Kang I. T-Cell biology in aging, with a focus on lung disease. J Gerontol A Biol Sci Med Sci. 2012;67A:254–63.

    CAS  Google Scholar 

  50. Kang I, Hong MS, Nolasco H, Park SH, Dan JM, Choi JY, et al. Age-associated change in the frequency of memory CD4+ T cells impairs long term CD4+ T cell responses to influenza vaccine. J Immunol. 2004;173:673–81.

    PubMed  CAS  Google Scholar 

  51. Mora AL, Woods CR, Garcia A, Xu J, Rojas M, Speck SH, et al. Lung infection with gamma-herpesvirus induces progressive pulmonary fibrosis in Th2-biased mice. Am J Physiol Lung Cell Mol Physiol. 2005;289:L711–21.

    PubMed  CAS  Google Scholar 

  52. Selman M, Rojas M, Mora AL, Pardo A. Aging and interstitial lung diseases: unraveling an old forgotten player in the pathogenesis of lung fibrosis. Semin Respir Crit Care Med. 2010;31:607–17.

    PubMed  Google Scholar 

  53. Volkova M, Zhang Y, Shaw AC, Lee PJ. The role of Toll-like receptors in age-associated lung diseases. J Gerontol A Biol Sci Med Sci. 2012;67A:247–53.

    CAS  Google Scholar 

  54. Jane-Wit D, Chun HJ. Mechanisms of dysfunction in senescent pulmonary endothelium. J Gerontol A Biol Sci Med Sci. 2012;67:236–41.

    PubMed  Google Scholar 

  55. Lepeule J, Baccarelli A, Motta V, Cantone L, Litonjua AA, Sparrow D, et al. Gene promoter methylation is associated with lung function in the elderly: the normative aging study. Epigenetics. 2012;7:261–9.

    PubMed  CAS  Google Scholar 

  56. Raghu G, Weycker D, Edelsberg J, Bradford WZ, Oster G. Incidence and prevalence of idiopathic pulmonary fibrosis. Am J Respi Crit Care Med. 2006;174:810–16.

    Google Scholar 

  57. Noth I, Martinez FJ. Recent advances in idiopathic pulmonary fibrosis. Chest. 2007;132:637–50.

    PubMed  Google Scholar 

  58. Copley SJ, Wells AU, Hawtin KE, Gibson DJ, Hodson JM, Jacques AE, et al. Lung morphology in the elderly: comparative CT study of subjects over 75 years old versus those under 55 years old. Radiology. 2009;251:566–73.

    PubMed  Google Scholar 

  59. Washko GR, Hunninghake GM, Fernandez IE, Nishino M, Okajima Y, Yamashiro T, et al. COPDGene investigators. Lung volumes and emphysema in smokers with interstitial lung abnormalities. N Engl J Med. 2011;364:897–906.

    PubMed  CAS  Google Scholar 

  60. Kuwano K, Hagimoto N, Maeyama T, Fujita M, Yoshimi M, Inoshima I, et al. Mitochondria-mediated apoptosis of lung epithelial cells in idiopathic interstitial pneumonias. Lab Invest. 2002;82:1695–706.

    PubMed  CAS  Google Scholar 

  61. Bellocq A, Azoulay E, Marullo S, Flahault A, Fouqueray B, Philippe C, et al. Reactive oxygen and nitrogen intermediates increase transforming growth factor-beta1 release from human epithelial alveolar cells through two different mechanisms. Am J Respir Cell Mol Biol. 1999;21:128–36.

    PubMed  CAS  Google Scholar 

  62. Barcellos-Hoff MH, Dix TA. Redox-mediated activation of latent transforming growth factor-beta 1. Mol Endocrinol. 1996;10:1077–83.

    PubMed  CAS  Google Scholar 

  63. Hybertson BM, Gao B, Bose SK, McCord JM. Oxidative stress in health and disease: the therapeutic potential of Nrf2 activation. Mol Aspects Med. 2011;32:234–46.

    PubMed  CAS  Google Scholar 

  64. Kikuchi N, Ishii Y, Morishima Y, Yageta Y, Haraguchi N, Itoh K, et al. Nrf2 protects against pulmonary fibrosis by regulating the lung oxidant level and Th1/Th2 balance. Respir Res. 2010;11:31.

    PubMed  Google Scholar 

  65. Markart P, Luboeinski T, Korfei M, Schmidt R, Wygrecka M, Mahavadi P, et al. Alveolar oxidative stress is associated with elevated levels of nonenzymatic low-molecular-weight antioxidants in patients with different forms of chronic fibrosing interstitial lung diseases. Antioxid Redox Signal. 2009;11:227–40.

    PubMed  CAS  Google Scholar 

  66. Artaud-Macari E, Goven D, Brayer S, Hamimi A, Besnard V, Marchal-Somme J, et al. Nrf2 nuclear translocation induces myofibroblastic dedifferentiation in idiopathic pulmonary fibrosis. Antioxid Redox Signal. 2013;18(1):66–79.

    PubMed  CAS  Google Scholar 

  67. Korfei M, Ruppert C, Mahavadi P, Henneke I, Markart P, Koch M, et al. Epithelial endoplasmic reticulum stress and apoptosis in sporadic idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2008;178:838–46.

    PubMed  CAS  Google Scholar 

  68. Lawson WE, Crossno PF, Polosukhin VV, Roldan J, Cheng DS, Lane KB, 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:L1119–26.

    PubMed  CAS  Google Scholar 

  69. Lawson WE, Cheng DS, Degryse AL, Tanjore H, Polosukhin VV, Xu XC, et al. Endoplasmic reticulum stress enhances fibrotic remodeling in the lungs. Proc Natl Acad Sci USA. 2011;108:10562–67.

    PubMed  CAS  Google Scholar 

  70. Naidoo N. ER and aging-protein folding and the ER stress response. Ageing Res Rev. 2009;8:150–9.

    PubMed  CAS  Google Scholar 

  71. Hussain SG, Ramaiah KV. Reduced eIF2alpha phosphorylation and increased proapoptotic proteins in aging. Biochem Biophys Res Commun. 2007;355:365–70.

    PubMed  CAS  Google Scholar 

  72. Kim SI, Na HJ, Ding Y, Wang Z, Lee SJ, Choi ME. Autophagy promotes intracellular degradation of type I collagen induced by transforming growth factor (TGF)-β1. J Biol Chem. 2012;287:11677–88.

    PubMed  CAS  Google Scholar 

  73. Hernández-Gea V, Ghiassi-Nejad Z, Rozenfeld R, Gordon R, Fiel MI, Yue Z, et al. Autophagy releases lipid that promotes fibrogenesis by activated hepatic stellate cells in mice and in human tissues. Gastroenterology. 2012;142:938–46.

    PubMed  Google Scholar 

  74. Yang HZ, Wang JP, Mi S, Liu HZ, Cui B, Yan HM, et al. TLR4 activity is required in the resolution of pulmonary inflammation and fibrosis after acute and chronic lung injury. Am J Pathol. 2012;180:275–92.

    PubMed  CAS  Google Scholar 

  75. Patel AS, Lin L, Geyer A, Haspel JA, An CH, Cao J, et al. Autophagy in idiopathic pulmonary fibrosis. PLoS One. 2012;7(7):e41394.

    PubMed  CAS  Google Scholar 

  76. Hua Y, Zhang Y, Ceylan-Isik AF, Wold LE, Nunn JM, Ren J. Chronic Akt activation accentuates aging-induced cardiac hypertrophy and myocardial contractile dysfunction: role of autophagy. Basic Res Cardiol. 2011;106:1173–91.

    PubMed  CAS  Google Scholar 

  77. Chen ZH, Kim HP, Sciurba FC, Lee SJ, Feghali-Bostwick C, Stolz DB, et al. Egr-1 regulates autophagy in cigarette smoke-induced chronic obstructive pulmonary disease. PLoS One. 2008;3(10):e3316.

    PubMed  Google Scholar 

  78. Blasco MA. Telomere length, stem cells and aging. Nat Chem Biol. 2007;3:640–9.

    PubMed  CAS  Google Scholar 

  79. Armanios MY, Chen JJ, Cogan JD, Alder JK, Ingersoll RG, Markin C, et al. Telomerase mutations in families with idiopathic pulmonary fibrosis. N Engl J Med. 2007;356:1317–26.

    PubMed  CAS  Google Scholar 

  80. Tsakiri KD, Cronkhite JT, Kuan PJ, Xing C, Raghu G, Weissler JC, et al. Adult-onset pulmonary fibrosis caused by mutations in telomerase. Proc Natl Acad Sci USA. 2007;104:7552–7.

    PubMed  CAS  Google Scholar 

  81. Alder JK, Chen JJ, Lancaster L, Danoff S, Su SC, Cogan JD, et al. Short telomeres are a risk factor for idiopathic pulmonary fibrosis. Proc Natl Acad Sci USA. 2008;105:13051–6.

    PubMed  CAS  Google Scholar 

  82. Savale L, Chaouat A, Bastuji-Garin S, Marcos E, Boyer L, Maitre B, et al. Shortened telomeres in circulating leukocytes of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2009;179:566–71.

    PubMed  CAS  Google Scholar 

  83. Lee J, Reddy R, Barsky L, Scholes J, Chen H, Shi W, et al. Lung alveolar integrity is compromised by telomere shortening in telomerase-null mice. Am J Physiol. 2009;296:L57–70.

    CAS  Google Scholar 

  84. Degryse AL, Xu XC, Newman JL, Mitchell DB, Tanjore H, Polosukhin VV, et al. Telomerase deficiency does not alter bleomycin-induced fibrosis in mice. Exp Lung Res. 2012;38:124–34.

    PubMed  CAS  Google Scholar 

  85. Rabinovich EI, Kapetanaki MG, Steinfeld I, Gibson KF, Pandit KV, Yu G, et al. Global methylation patterns in idiopathic pulmonary fibrosis. PLoS One. 2012;7(4):e33770.

    PubMed  CAS  Google Scholar 

  86. Sanders YY, Ambalavanan N, Halloran B, Zhang X, Liu H, Crossman DK, et al. Altered DNA methylation profile in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2012;186(6):525–35.

    PubMed  CAS  Google Scholar 

  87. Trujillo G, Meneghin A, Flaherty KR, Sholl LM, Myers JL, Kazerooni EA, et al. TLR9 differentiates rapidly from slowly progressing forms of idiopathic pulmonary fibrosis. Sci Transl Med. 2010;2:57ra82.

    PubMed  CAS  Google Scholar 

  88. Rege TA, Hagood JS. Thy-1, a versatile modulator of signaling affecting cellular adhesion, proliferation, survival, and cytokine/growth factor responses. Biochim Biophys Acta. 2006;1763:991–9.

    PubMed  CAS  Google Scholar 

  89. Ramírez G, Hagood JS, Sanders Y, Ramírez R, Becerril C, Segura L, et al. Absence of Thy-1 results in TGF-β induced MMP-9 expression and confers a profibrotic phenotype to human lung fibroblasts. Lab Invest. 2011;91:1206–18.

    PubMed  Google Scholar 

  90. Sanders YY, Pardo A, Selman M, Nuovo GJ, Tollefsbol TO, Siegal GP, et al. Thy-1 promoter hypermethylation: a novel epigenetic pathogenic mechanism in pulmonary fibrosis. Am J Respir Cell Mol Biol. 2008;39:610–18.

    PubMed  CAS  Google Scholar 

  91. Sanders YY, Tollefsbol TO, Varisco BM, Hagood JS. Epigenetic regulation of thy-1 by histone deacetylase inhibitor in rat lung fibroblasts. Am J Respir Cell Mol Biol. 2011;45:16–23.

    PubMed  CAS  Google Scholar 

  92. Cisneros J, Hagood J, Checa M, Ortiz-Quintero B, Negreros M, Herrera I, et al. Hypermethylation-mediated silencing of p14ARF in fibroblasts from idiopathic pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol. 2012;303(4):L295–303.

    PubMed  CAS  Google Scholar 

  93. Coward WR, Watts K, Feghali-Bostwick CA, Knox A, Pang L. Defective histone acetylation is responsible for the diminished expression of cyclooxygenase 2 in idiopathic pulmonary fibrosis. Mol Cell Biol. 2009;29:4325–39.

    PubMed  CAS  Google Scholar 

  94. Thiery JP, Acloque H, Huang RY, Nieto MA. Epithelial-mesenchymal transitions in development and disease. Cell. 2009;139:871–90.

    PubMed  CAS  Google Scholar 

  95. King Jr TE, Pardo A, Selman M. Idiopathic pulmonary fibrosis. Lancet. 2011;378:1949–61.

    PubMed  Google Scholar 

  96. Willis BC, Liebler JM, Luby-Phelps K, Nicholson AG, Crandall ED, du Bois RM, et al. Induction of epithelial-mesenchymal transition in alveolar epithelial cells by transforming growth factor-beta1: potential role in idiopathic pulmonary fibrosis. Am J Pathol. 2005;166:1321–32.

    PubMed  CAS  Google Scholar 

  97. Kim KK, Kugler MC, Wolters PJ, Robillard L, Galvez MG, Brumwell AN, et al. Alveolar epithelial cell mesenchymal transition develops in vivo during pulmonary fibrosis and is regulated by the extracellular matrix. Proc Natl Acad Sci USA. 2006;103:13180–85.

    PubMed  CAS  Google Scholar 

  98. Rock JR, Barkauskas CE, Cronce MJ, Xue Y, Harris JR, Liang J, et al. Multiple stromal populations contribute to pulmonary fibrosis without evidence for epithelial to mesenchymal transition. Proc Natl Acad Sci USA. 2011;108:E1475–83.

    PubMed  CAS  Google Scholar 

  99. McDonald OG, Wu H, Timp W, Doi A, Feinberg AP. Genome-scale epigenetic reprogramming during epithelial-to-mesenchymal transition. Nat Struct Mol Biol. 2011;18:867–74.

    PubMed  CAS  Google Scholar 

  100. Laberge RM, Awad P, Campisi J, Desprez PY. Epithelial-mesenchymal transition induced by senescent fibroblasts. Cancer Microenviron. 2012;5:39–44.

    PubMed  CAS  Google Scholar 

  101. Smit MA, Peeper DS. Epithelial-mesenchymal transition and senescence: two cancer-related processes are crossing paths. Aging (Albany NY). 2010;2:735–41.

    CAS  Google Scholar 

  102. van Rooij E, Sutherland LB, Thatcher JE, DiMaio JM, Naseem RH, Marshall WS, et al. Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis. Proc Natl Acad Sci USA. 2008;105:13027–32.

    PubMed  Google Scholar 

  103. Thum T, Gross C, Fiedler J, Fischer T, Kissler S, Bussen M, et al. MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature. 2008;456:980–4.

    PubMed  CAS  Google Scholar 

  104. Pandit KV, Corcoran D, Yousef H, Yarlagadda M, Tzouvelekis A, Gibson KF, et al. Inhibition and role of let-7d in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2010;182:220–9.

    PubMed  CAS  Google Scholar 

  105. Liu G, Friggeri A, Yang Y, Milosevic J, Ding Q, Thannickal VJ, et al. miR-21 mediates fibrogenic activation of pulmonary fibroblasts and lung fibrosis. J Exp Med. 2010;207:1589–97.

    PubMed  CAS  Google Scholar 

  106. Kato M, Zhang J, Wang M, Lanting L, Yuan H, Rossi JJ, Natarajan R. MicroRNA-192 in diabetic kidney glomeruli and its function in TGF-beta-induced collagen expression via inhibition of E-box repressors. Proc Natl Acad Sci USA. 2007;104:3432–37.

    PubMed  CAS  Google Scholar 

  107. Shan H, Zhang Y, Lu Y, Zhang Y, Pan Z, Cai B, et al. Downregulation of miR-133 and miR-590 contributes to nicotine-induced atrial remodelling in canines. Cardiovasc Res. 2009;83:465–72.

    PubMed  CAS  Google Scholar 

  108. Duisters RF, Tijsen AJ, Schroen B, Leenders JJ, Lentink V, van der Made I, et al. miR-133 and miR-30 regulate connective tissue growth factor: implications for a role of microRNAs in myocardial matrix remodeling. Circ Res. 2009;104:170–8.

    PubMed  CAS  Google Scholar 

  109. Cordes KR, Sheehy NT, White MP, Berry EC, Morton SU, Muth AN, et al. miR-145 and miR-143 regulate smooth muscle cell fate and plasticity. Nature. 2009;460:705–10.

    PubMed  CAS  Google Scholar 

  110. Cushing L, Kuang PP, Qian J, Shao F, Wu J, Little F, et al. MIR-29 is a major regulator of genes associated with pulmonary fibrosis. Am J Respir Cell Mol Biol. 2011;45:287–94.

    PubMed  CAS  Google Scholar 

  111. Pottier N, Maurin T, Chevalier B, Puisségur MP, Lebrigand K, Robbe-Sermesant K, et al. Identification of keratinocyte growth factor as a target of microRNA-155 in lung fibroblasts: implication in epithelial-mesenchymal interactions. PLoS One. 2009;4(8):e6718.

    PubMed  Google Scholar 

  112. Martin MM, Lee EJ, Buckenberger JA, Schmittgen TD, Elton TS. MicroRNA-155 regulates human angiotensin II type 1 receptor expression in fibroblasts. J Biol Chem. 2006;281:18277–84.

    PubMed  CAS  Google Scholar 

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Acknowledgment

Our research was partially supported by PAPIIT IN214612.

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Authors and Affiliations

  1. Dirección de Investigación, Instituto Nacional de Enfermedades Respiratorias, Ismael Cosio Villegas, Tlalpan 4502, México D.F, 14080, Mexico

    Moisés Selman M.D.

  2. Facultad de Ciencias, Laboratorio de Bioquímica, Universidad Nacional Autónoma de México, México D.F., Mexico

    Yair Romero M.Sc. & Annie Pardo Ph.D.

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  1. Moisés Selman M.D.
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  2. Yair Romero M.Sc.
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  3. Annie Pardo Ph.D.
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Correspondence to Moisés Selman M.D. .

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  1. Dept. Internal Medicine, Sect. Allergy Pulmonary & Critical Care Med., University of Wisconsin School of Medicine & Public Health, Madison, Wisconsin, USA

    Keith C. Meyer

  2. Advanced Lung Disease and Lung Transplant Program, Inova Fairfax Hospital, Falls Church, Virginia, USA

    Steven D. Nathan

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© 2014 Springer Science+Business Media New York

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Selman, M., Romero, Y., Pardo, A. (2014). Aging and IPF: What Is the Link?. In: Meyer, K., Nathan, S. (eds) Idiopathic Pulmonary Fibrosis. Respiratory Medicine, vol 9. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-682-5_12

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  • DOI: https://doi.org/10.1007/978-1-62703-682-5_12

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-681-8

  • Online ISBN: 978-1-62703-682-5

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