Skip to main content

Advertisement

Log in

The Role of Aging in Idiopathic Pulmonary Fibrosis

  • Published:
Lung Aims and scope Submit manuscript

Abstract

Idiopathic pulmonary fibrosis (IPF) has been gathering interest in recent years and as such this review will focus on the potential contributions that age plays on its onset and prevalence. Environmental stress over time caused by the inhalation of foreign substances results in subsequent damage and repair of lung tissue. This damage prematurely causes a decrease in stem cell differentiation potential. In conjunction with declining proliferation, the correlation between age and general attenuation of the immune system allows for the introduction of viral components such as the Epstein–Barr virus which has been associated with lung injury, a causation which has not yet been investigated. But, regardless of environmental factors, cellular alterations due to, or in correlation with, age could result in the onset or prolonging of IPF. General genetic mutation and epigenetic methylations accumulate over a person’s lifespan while miRNA expression changes from birth to adulthood. This collection of alterations over time may cause dysregulation of expressed genetic material which can result in many age-related diseases including pulmonary fibrosis. Such alterations would be prevented by autophagy or cell-mediated apoptosis, but due to age-related dysregulations, these systems function at a diminished capacity. On the cellular level, the end result is an accumulation of dysfunctional organelles with damaged molecules, such as reactive oxygen species, and general genetic and epigenetic alterations resulting in excess generation of fibrous tissue and overall damage to the pulmonary system.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Kim DS, Collard HR, King TE Jr (2006) Classification and natural history of the idiopathic interstitial pneumonias. Proc Am Thorac Soc 3(4):285–292

    Article  PubMed Central  PubMed  Google Scholar 

  2. Hashemi Sadraei N, Riahi T, Masjedi MR (2013) Idiopathic pulmonary fibrosis in a referral center in Iran: are patients developing the disease at a younger age? Arch Iran Med 16(3):177–181

    PubMed  Google Scholar 

  3. Turn CS, Lockey RF, Kolliputi N (2015) Putting the brakes on age-related idiopathic pulmonary fibrosis: can Nox4 inhibitors suppress IPF? Exp Gerontol 63:81–82

    Article  CAS  PubMed  Google Scholar 

  4. Torres-Gonzalez E et al (2012) Role of endoplasmic reticulum stress in age-related susceptibility to lung fibrosis. Am J Respir Cell Mol Biol 46(6):748–756

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Huang WT et al (2015) Plasminogen activator inhibitor 1, fibroblast apoptosis resistance, and aging-related susceptibility to lung fibrosis. Exp Gerontol 61:62–75

    Article  CAS  PubMed  Google Scholar 

  6. Taskar VS, Coultas DB (2006) Is idiopathic pulmonary fibrosis an environmental disease? Proc Am Thorac Soc 3(4):293–298

    Article  PubMed  Google Scholar 

  7. Chilosi M et al (2010) Epithelial stem cell exhaustion in the pathogenesis of idiopathic pulmonary fibrosis. Sarcoidosis Vasc Diffuse Lung Dis 27(1):7–18

    CAS  PubMed  Google Scholar 

  8. Trusina A (2014) Stress induced telomere shortening: longer life with less mutations? BMC Syst Biol 8:27

    Article  PubMed Central  PubMed  Google Scholar 

  9. Doyle TJ et al (2012) The expanding role of biomarkers in the assessment of smoking-related parenchymal lung diseases. Chest 142(4):1027–1034

    Article  PubMed Central  PubMed  Google Scholar 

  10. Stevenson CS et al (2007) Comprehensive gene expression profiling of rat lung reveals distinct acute and chronic responses to cigarette smoke inhalation. Am J Physiol Lung Cell Mol Physiol 293(5):L1183–L1193

    Article  CAS  PubMed  Google Scholar 

  11. Churg A et al (2009) Expression of profibrotic mediators in small airways versus parenchyma after cigarette smoke exposure. Am J Respir Cell Mol Biol 40(3):268–276

    Article  CAS  PubMed  Google Scholar 

  12. Williams KJ et al (2007) Equine multinodular pulmonary fibrosis: a newly recognized herpesvirus-associated fibrotic lung disease. Vet Pathol 44(6):849–862

    Article  CAS  PubMed  Google Scholar 

  13. Hansen S (2015) A review of the equine age-related changes in the immune system: comparisons between human and equine aging, with focus on lung-specific immune-aging. Ageing Res Rev 20c:11–23

    Article  Google Scholar 

  14. Maruyama M (2013) Age-associated decline in the immune system. Nihon Rinsho 71(6):993–998

    PubMed  Google Scholar 

  15. Marzouk K et al (2005) Epstein-Barr-virus-induced interstitial lung disease. Curr Opin Pulm Med 11(5):456–460

    Article  PubMed  Google Scholar 

  16. Mora AL, Roman J (2010) Virus-related interstitial lung disease. In: King TE Jr, Schwarz MI (eds) Interstitial lung disease. BC Decker, Hamilton, pp 251–265

    Google Scholar 

  17. Kelly BG et al (2002) A rearranged form of Epstein-Barr virus DNA is associated with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 166(4):510–513

    Article  PubMed  Google Scholar 

  18. Tang YW et al (2003) Herpesvirus DNA is consistently detected in lungs of patients with idiopathic pulmonary fibrosis. J Clin Microbiol 41(6):2633–2640

    Article  PubMed Central  PubMed  Google Scholar 

  19. Alison MR, Sarraf CE (1992) Apoptosis: a gene-directed programme of cell death. J R Coll Phys Lond 26(1):25–35

    CAS  Google Scholar 

  20. Behrens A et al (2014) Impact of genomic damage and ageing on stem cell function. Nat Cell Biol 16(3):201–207

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Thomas AQ et al (2002) 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 165(9):1322–1328

    Article  PubMed  Google Scholar 

  22. Lawson WE et al (2008) 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 294(6):L1119–L1126

    Article  CAS  PubMed  Google Scholar 

  23. Vaidya A et al (2014) Knock-in reporter mice demonstrate that DNA repair by non-homologous end joining declines with age. PLoS Genet 10(7):e1004511

    Article  PubMed Central  PubMed  Google Scholar 

  24. Thannickal VJ (2013) Mechanistic links between aging and lung fibrosis. Biogerontology 14(6):609–615

    Article  CAS  PubMed  Google Scholar 

  25. Brunet A, Berger SL (2014) Epigenetics of aging and aging-related disease. J Gerontol A Biol Sci Med Sci 69(Suppl 1):S17–S20

    Article  PubMed Central  PubMed  Google Scholar 

  26. Ono T et al (1985) Dysdifferentiative nature of aging: age-dependent expression of MuLV and globin genes in thymus, liver and brain in the AKR mouse strain. Gerontology 31(6):362–372

    Article  CAS  PubMed  Google Scholar 

  27. Johnson AA et al (2012) The role of DNA methylation in aging, rejuvenation, and age-related disease. Rejuvenation Res 15(5):483–494

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Bird A (2002) DNA methylation patterns and epigenetic memory. Genes Dev 16(1):6–21

    Article  CAS  PubMed  Google Scholar 

  29. Taskar V, Coultas D (2008) Exposures and idiopathic lung disease. Semin Respir Crit Care Med 29(6):670–679

    Article  PubMed  Google Scholar 

  30. Pandit KV et al (2010) Inhibition and role of let-7d in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 182(2):220–229

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. McCauley BS, Dang W (2014) Histone methylation and aging: lessons learned from model systems. Biochim Biophys Acta 1839(12):1454–1462

    Article  CAS  PubMed  Google Scholar 

  32. Langton AK, Herrick SE, Headon DJ (2008) An extended epidermal response heals cutaneous wounds in the absence of a hair follicle stem cell contribution. J Invest Dermatol 128(5):1311–1318

    Article  CAS  PubMed  Google Scholar 

  33. Kim M et al (2010) DNA methylation as a biomarker for cardiovascular disease risk. PLoS One 5(3):e9692

    Article  PubMed Central  PubMed  Google Scholar 

  34. Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136(2):215–233

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Williams AE (2008) Functional aspects of animal microRNAs. Cell Mol Life Sci 65(4):545–562

    Article  CAS  PubMed  Google Scholar 

  36. Izzotti A et al (2009) Relationships of microRNA expression in mouse lung with age and exposure to cigarette smoke and light. FASEB J 23(9):3243–3250

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Li P et al (2013) Serum miR-21 and miR-155 expression in idiopathic pulmonary fibrosis. J Asthma 50(9):960–964

    Article  CAS  PubMed  Google Scholar 

  38. Nho RS et al (2014) MicroRNA-96 inhibits FoxO3a function in IPF fibroblasts on type I collagen matrix. Am J Physiol Lung Cell Mol Physiol 307(8):L632–L642

    Article  CAS  PubMed  Google Scholar 

  39. Tsakiri KD et al (2007) Adult-onset pulmonary fibrosis caused by mutations in telomerase. Proc Natl Acad Sci USA 104(18):7552–7557

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  40. Waisberg DR et al (2010) Abnormal expression of telomerase/apoptosis limits type II alveolar epithelial cell replication in the early remodeling of usual interstitial pneumonia/idiopathic pulmonary fibrosis. Hum Pathol 41(3):385–391

    Article  PubMed  Google Scholar 

  41. Driscoll B et al (2000) Telomerase in alveolar epithelial development and repair. Am J Physiol Lung Cell Mol Physiol 279(6):L1191–L1198

    CAS  PubMed  Google Scholar 

  42. Valdes AM et al (2005) Obesity, cigarette smoking, and telomere length in women. Lancet 366(9486):662–664

    Article  CAS  PubMed  Google Scholar 

  43. Roobrouck VD, Ulloa-Montoya F, Verfaillie CM (2008) Self-renewal and differentiation capacity of young and aged stem cells. Exp Cell Res 314(9):1937–1944

    Article  CAS  PubMed  Google Scholar 

  44. Choumerianou DM et al (2010) Comparative study of stemness characteristics of mesenchymal cells from bone marrow of children and adults. Cytotherapy 12(7):881–887

    Article  PubMed  Google Scholar 

  45. Mora AL, Rojas M (2013) Adult stem cells for chronic lung diseases. Respirology 18(7):1041–1046

    PubMed  Google Scholar 

  46. Phadwal K, Watson AS, Simon AK (2013) Tightrope act: autophagy in stem cell renewal, differentiation, proliferation, and aging. Cell Mol Life Sci 70(1):89–103

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  47. Selman M, Pardo A (2014) Revealing the pathogenic and aging-related mechanisms of the enigmatic idiopathic pulmonary fibrosis. An integral model. Am J Respir Crit Care Med 189(10):1161–1172

    Article  CAS  PubMed  Google Scholar 

  48. Yang IV (2012) Epigenomics of idiopathic pulmonary fibrosis. Epigenomics 4(2):195–203

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  49. Selman M et al (2010) Aging and interstitial lung diseases: unraveling an old forgotten player in the pathogenesis of lung fibrosis. Semin Respir Crit Care Med 31(5):607–617

    Article  PubMed  Google Scholar 

  50. Hagimoto N et al (1997) Apoptosis and expression of Fas/Fas ligand mRNA in bleomycin-induced pulmonary fibrosis in mice. Am J Respir Cell Mol Biol 16(1):91–101

    Article  CAS  PubMed  Google Scholar 

  51. Lee CG et al (2004) Early growth response gene 1-mediated apoptosis is essential for transforming growth factor beta1-induced pulmonary fibrosis. J Exp Med 200(3):377–389

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  52. Gilhar A et al (2004) Aging of human epidermis: reversal of aging changes correlates with reversal of keratinocyte fas expression and apoptosis. J Gerontol A Biol Sci Med Sci 59(5):411–415

    Article  PubMed  Google Scholar 

  53. Mercado N, Ito K, Barnes PJ (2015) Accelerated ageing of the lung in COPD: new concepts. Thorax. doi:10.1136/thoraxjnl-2014-206084

    PubMed  Google Scholar 

  54. Patel AS et al (2012) Autophagy in idiopathic pulmonary fibrosis. PLoS One 7(7):e41394

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  55. He LQ, Lu JH, Yue ZY (2013) Autophagy in ageing and ageing-associated diseases. Acta Pharmacol Sin 34(5):605–611

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  56. Zhang HJ et al (2003) Heat-induced liver injury in old rats is associated with exaggerated oxidative stress and altered transcription factor activation. FASEB J 17(15):2293–2295

    CAS  PubMed  Google Scholar 

  57. Kregel KC, Zhang HJ (2007) An integrated view of oxidative stress in aging: basic mechanisms, functional effects, and pathological considerations. Am J Physiol Regul Integr Comp Physiol 292(1):R18–R36

    Article  CAS  PubMed  Google Scholar 

  58. Hagen TM (2003) Oxidative stress, redox imbalance, and the aging process. Antioxid Redox Signal 5(5):503–506

    Article  CAS  PubMed  Google Scholar 

  59. Kinnula VL et al (2005) Oxidative stress in pulmonary fibrosis: a possible role for redox modulatory therapy. Am J Respir Crit Care Med 172(4):417–422

    Article  PubMed Central  PubMed  Google Scholar 

  60. Faner R et al (2012) Abnormal lung aging in chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 186(4):306–313

    Article  CAS  PubMed  Google Scholar 

  61. Bocchino M et al (2010) Reactive oxygen species are required for maintenance and differentiation of primary lung fibroblasts in idiopathic pulmonary fibrosis. PLoS One 5(11):e14003

    Article  PubMed Central  PubMed  Google Scholar 

  62. Hecker L et al (2014) Reversal of persistent fibrosis in aging by targeting Nox4-Nrf2 redox imbalance. Sci Transl Med 6(231):231ra47

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

NK was funded by the American Heart Association National Scientist Development Grant 09SDG2260957 and National Institutes of Health R01 HL105932 and the Joy McCann Culverhouse Endowment to the Division of Allergy and Immunology.

Conflict of interest

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Narasaiah Kolliputi.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Leung, J., Cho, Y., Lockey, R.F. et al. The Role of Aging in Idiopathic Pulmonary Fibrosis. Lung 193, 605–610 (2015). https://doi.org/10.1007/s00408-015-9729-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00408-015-9729-3

Keywords

Navigation