Features of the bronchopulmonary system in elderly individuals: Aging and the respiratory system

The elderly population is growing. It is projected to reach 20% or even higher percentage of the population by 2050. Respiratory system diseases rank second among the causes of death worldwide. To date, several signs of aging have been described which underlie the structural morphological and functional changes that lead to a gradual decline in the functions of the entire organism and disruption of adaptive mechanisms. This article describes some mechanisms of cellular senescence, provides morphofunctional characteristics of the senile lung, outlines the features of the course of certain respiratory diseases in elderly individuals, and presents some research results in the field of senotherapeutic drug development. Structural morphological, functional, and immunological age related changes, combined with external damaging factors and comorbidities, contribute to the development of oncological processes, chronic obstructive pulmonary disease, emphysema, respiratory infections, idiopathic pulmonary fibrosis, and other conditions. The development and study of senotherapeutic drugs are actively underway. However, these studies have a short follow-up period, and there is still insufficient research specifically in pulmonology. Due to the relevance of health in citizens over 65 years of age and the active longevity, the Russian Federation has a number of social programs, while the scientific community is seeing a growing number of related studies and developments. The aim is to update scientific understanding of age-related changes in the respiratory system from the molecular to the systemic level and their relationship with the characteristics of respiratory pathology in the elderly. Conclusion. Age-related changes occurring at the molecular and cellular level lead to various disorders of organs and systems, including the respiratory system. The development of comorbid pathology makes an elderly person vulnerable to external influences, reduces the quality of life, complicates the course of diseases, and complicates their treatment. The possibility of using senotherapeutic drugs and their effectiveness requires confirmation in clinical studies.

1. Karuso C., Candore D., eds. [Human aging: from cellular processes to life extension strategies]. Moscow: GEOTAR-Media; 2025 (in Russian).

2. López-Otín C., Blasco M.A., Partridge L. et al. Hallmarks of aging: an expanding universe. Cell. 2023; 186 (2): 243–278. DOI: 10.1016/j.cell.2022.11.001.

3. Miller K.N., Victorelli S.G., Salmonowicz H. et al. Cytoplasmic DNA: sources, sensing, and role in aging and disease. Cell. 2021; 184 (22): 5506–5526. DOI: 10.1016/j.cell.2021.09.034.

4. Kytikova O.Yu., Gvozdenko T.A., Vitkina T.I., Novgorodtsev A.D. [Genotoxic effect of oxidative stress in elderly patients with chronic obstructive pulmonary disease]. Byulleten′ fiziologii i patologii dykhaniya. 2015; (56): 46–49. Available at: https://cfpd.elpub.ru/jour/article/view/696 (in Russian).

5. Dausheva A.Kh., Zarubina E.G., Bogdanova Yu.V. [Genetic markers of endothelial dysfunction in chronic obstructive pulmonary disease]. Tikhookeanskiy meditsinskiy zhurnal. 2024; (1): 48–52. DOI: 10.34215/1609-1175-2024-1-48-52 (in Russian).

6. Demidova I.A., Barinov A.A., Savelov N.A. et al. [Study of molecular genetic disorders in patients with lung ademocarcinoma]. Onkologiya. Zhurnal imeny P.A.Gertsena. 2012; 1 (2): 28–34. Available at: https://www.mediasphera.ru/issues/onkologiya-zhurnal-im-p-agertsena/2012/2/downloads/ru/032305-218X201225 (in Russian).

7. Hipp M.S., Kasturi P., Hartl F.U. The proteostasis network and its decline in ageing. Nat. Rev. Mol. Cell Biol. 2019; 20 (7): 421–435. DOI:10.1038/s41580-019-0101-y.

8. Polyakova V.S., Borkina A.N. [Morphofunctional characteristics of bronchiolar exocrine cells (Clara cells) in adults]. Morfologiya. 2008; 134 (5): 36–39. Available at: https://www.elibrary.ru/item.asp?id=11618367 (in Russian).

9. Moroz V.V., Golubev A.M., Kuzovlev A.N. et al. [Clara cell protein (Club cell protein) is a new diagnostic molecular candidate biomarker in nosocomial pneumonia]. Obshchaya reanimatologiya. 2014; 10 (6): 6–14. DOI: 10.15360/1813-9779-2014-6-6-14 (in Russian).

10. Metelskaya V.A., Timofeev Yu.S., Neshkova E.A. et al. [Inflammatory aging. Part 1. The principal biochemical mechanisms]. Profilakticheskaya meditsina. 2024; 27 (12): 145–150. DOI: 10.17116/profmed202427121145 (in Russian).

11. Kosheleva O.K., Zairatyants O.V., Chernyaev A.L., Malyavin A.G. [Current concepts of chronic obstructive pulmonary disease and senile lungs]. Arkhiv patologii. 2013; 75 (4): 37–41. Available at: https://www.mediasphera.ru/issues/arkhiv-patologii/2020/4/1000419552013041037 (in Russian).

12. Janssen R., Piscaer I., Franssen F.M.E., Wouters E.F.M. Emphysema: looking beyond alpha-1 antitrypsin deficiency. Expert Rev. Respir. Med. 2019; 13 (4): 381–397. DOI: 10.1080/17476348.2019.1580575.

13. Fomchenko N.E., Voropaev E.V., Skachkov A.V., Zatora N.Yu. [The biological role of mitochondria in body aging]. Problemy zdorov′ya i ekologii. 2015; (4): 8–13. DOI: 10.51523/2708-6011.2015-12-4-2 (in Russian).

14. Wang Y., Huang X., Luo G. et al. The aging lung: microenvironment, mechanisms, and diseases. Front. Immunol. 2024; 15: 1383503. DOI: 10.3389/fimmu.2024.1383503.

15. Pal S., Tyler J. Epigenetics and aging. Sci. Adv. 2016; 2 (7): e1600584. DOI: 10.1126/sciadv.1600584.

16. Sokolov P.L., Chebanenko N.V., Mednaya D.M. [Epigenetic influences and brain development]. Zhurnal nevrologii i psikhiatrii imeny S.S.Korsakova. 2023; 123 (3): 12–19. DOI: 10.17116/jnevro202312303112 (in Russian).

17. Chuchalin A.G., Avdeev S.N., Aisanov Z.R. et al. [Federal guidelines on diagnosis and treatment of chronic obstructive pulmonary disease]. Pulmonologiya. 2022; 32 (3): 356–392. DOI: 10.18093/0869-0189-2022-32-3-356-392 (in Russian).

18. Ren L., Chang Y.F., Jiang S.H. et al. DNA methylation in idiopathic pulmonary fibrosis. Front. Cell Dev. Biol. 2024; 12: 1416325. DOI: 10.3389/fcell.2024.1416325.

19. Olovnikov A.I. A theory of marginotomy: the incomplete copying of template margin in enzymatic synthesis of polynucleotides and biological significance of the phenomenon. J. Theor. Biol. 1973; 41 (1): 181–190. DOI: 10.1016/0022-5193(73)90198-7.

20. Harley C., Liu W., Blasco M. et al. A natural product telomerase activator as part of a health maintenance program. Rejuvenation Res. 2011; 14 (1): 45–56. DOI: 10.1089/rej.2010.1085.

21. Smirnova M.S., Nekrasov A.A. [Idiopathic pulmonary fibrosis and aging]. Klinicheskaya gerontologiya. 2022; 28 (11–12): 63–69. DOI: 10.26347/1607-2499.2022.11-12.063-069 (in Russian).

22. Shchepikhin E.I., Zaytseva A.S., Shmelev E.I. et al. [Prospects for personalized therapy of interstitial lung diseases: focus on genotype-oriented approach]. Doctor.Ru. 2025; 24 (8): 79–85. DOI: 10.31550/1727-2378-2025-24-8-79-85 (in Russian).

23. Barnes P.J. Senescence in COPD and its comorbidities. Annu. Rev. Physiol. 2017; 79: 517–539. DOI: 10.1146/annurev-physiol.022516-034314.

24. Acosta J.C., Banito A., Wuestefeld T. et al. A complex secretory program orchestrated by the inflammasome controls paracrine senescence. Nat. Cell Biol. 2013; 15 (8): 978–990. DOI: 10.1038/ncb2784.

25. van Deursen J.M. The role of senescent cells in ageing. Nature. 2014; 509 (7501): 439–446. DOI: 10.1038/nature13193.

26. Gorgoulis V., Adams P.D., Alimonti A. et al. Cellular senescence: defining a path forward. Cell. 2019; 179 (4): 813–827. DOI: 10.1016/j.cell.2019.10.005.

27. Malygina N.A. [Cell aging and age related diseases]. Klinicheskaya gerontologiya. 2014; 20 (3–4): 30–34. Available at: https://cyberleninka.ru/article/n/starenie-kletok-i-vozrastzavisimye-zabolevaniya/viewer (in Russian).

28. Masyutina A.M., Pashchenkov M.V., Pinegin B.V. [Cellular senescence: mechanisms and clinical implications]. Immunologiya. 2024; 45 (2): 221–234. DOI: 10.33029/1816-2134-2024-45-2-221-234 (in Russian).

29. Karimov D.D., Kudoyarov E.R., Mukhammadiyeva G.F. et al. [Biomarkers of aging in the study of occupationally induced harmful exposures (literature review)]. Gigiyena i sanitariya. 2021; 100 (11): 1328–1332. DOI: 10.47470/0016-9900-2021-100-11-1328-1332 (in Russian).

30. Mustafin R.N. [Molecular genetics of idiopathic pulmonary fibrosis]. Vavilovskiy zhurnal genetiki i selektsii. 2022; 26 (3): 308–318. DOI: 10.18699/VJGB-22-37 (in Russian).

31. Babak S.L., Gorbunova M.V., Karnaushkina K.M. [Pulmonary senescence (aging): controversial issues]. Pharmateca. 2024; 31 (4): 105–114. DOI: 10.18565/pharmateca.2024.4.105-114 (in Russian).

32. Levine B., Kroemer G. Biological functions of autophagy genes: a disease perspective. Cell. 2019; 176 (1–2): 11–42. DOI: 10.1016/j.cell.2018.09.048.

33. Mora A.L., Bueno M., Rojas M. Mitochondria in the spotlight of aging and idiopathic pulmonary fibrosis. J. Clin. Invest. 2017; 127 (2): 405–414. DOI: 10.1172/JCI87440.

34. Borodkina A.V., Deryabin P.I., Gryukova A.A., Nikolsky N.N. [“Social life” of senescent cells: what is SASP and why study It?]. Acta Naturae. 2018; 10 (1): 4–14. DOI: 10.32607/20758251-2018-10-1-414 (in Russian).

35. Samarelli A.V., Tonelli R., Heijink I. et al. Dissecting the role of mesenchymal stem cells in idiopathic pulmonary fibrosis: cause or solution. Front. Pharmacol. 2021; 12: 692551. DOI: 10.3389/fphar.2021.692551.

36. Zaragosi L.E., Salwig I., Wasnick R.M. et al. Cellular plasticity and regenerative mechanisms in the lung. Eur. Respir. Rev. 2026; 35 (179): 250168. DOI: 10.1183/16000617.0168-2025.

37. Shaykhiev R. Airway basal cells in chronic obstructive pulmonary disease: a continuum or a dead end? Am. J. Respir. Cell Mol. Biol. 2021; 65 (1): 10–12. DOI: 10.1165/rcmb.2021-0150ED.

38. Baranova I.I., Leshchenko I.V. [COPD – what disease development factors remain in the shadows?]. Farmateka. 2018; 361 (8): 16–23. DOI: 10.18565/pharmateca.2018.8.16-23 (in Russian).

39. Kokaev R.I., Korniyeva S.S., Kerimova I.A. et al. [Pathogenetic mechanisms of idiopathic pulmonary fibrosis: a modern view on the role of genetic and epigenetic factors]. Vestnik sovremennoy klinicheskoy meditsiny. 2026; 19 (1): 123–132. DOI: 10.20969/VSKM.2026.19(1).123-132 (in Russian).

40. Carmona J.J., Michan S. Biology of healthy aging and longevity. Rev. Invest. Clin. 2016; 68 (1): 7–16. Available at: https://clinicalandtranslationalinvestigation.com/files/ric_2016_68_1_007-016.pdf

41. Chand H.S., Harris J.F., Mebratu Y. et al. Intracellular insulin-like growth factor-1 induces Bcl-2 expression in airway epithelial cells. J. Immunol. 2012; 188 (9): 4581–4589. DOI: 10.4049/jimmunol.1102673.

42. Takasaka N., Araya J., Hara H. et al. Autophagy induction by SIRT6 through attenuation of insulin-like growth factor signaling is involved in the regulation of human bronchial epithelial cell senescence. J. Immunol. 2014; 192 (3): 958–968. DOI: 10.4049/jimmunol.1302341.

43. Kamasheva G.R., Sineglazova A.V., Arkhipov E.V. [Morphofunctional aspects of aging that determine the course of respiratory diseases in elderly and senile age]. Vestnik sovremennoy klinicheskoy meditsiny. 2022; 15 (2): 95–102. DOI: 10.20969/vskm.2022.15(2).95-102 (in Russian).

44. Kozlov E.V., Derevyannykh E.V., Balashova N.A. et al. [The effect of socio-economic factors on the quality of life in patients with chronic obstructive lung disease in conditions of comorbidity]. Siberian Journal of Life Sciences and Agriculture. 2019; 11 (3): 103–120. DOI: 10.12731/2658-6649-2019-11-3-103-120 (in Russian).

45. Tkachenko A.V., Sokolova P.S., Aslonyants A.M., Dyakova D.A. [Toxic effect of heavy metals and ways to reduce their content in air]. Mezhdunarodnyy zhurnal eksperimental′nogo obrazovaniya. 2015; (11-6): 971–972. Available at: https://expeducation.ru/ru/article/view?id=9544 (in Russian).

46. Zuo L., He F., Sergakis G.G. et al. Interrelated role of cigarette smoking, oxidative stress, and immune response in COPD and corresponding treatments. Am. J. Physiol. Lung Cell Mol. Physiol. 2014; 307 (3): L205–218. DOI: 10.1152/ajplung.00330.2013.

47. Caramori G., Di Stefano A., Casolari P. et al. Chemokines and chemokine receptors blockers as new drugs for the treatment of chronic obstructive pulmonary disease. Curr. Med. Chem. 2013; 20 (35): 4317–4349. DOI: 10.2174/09298673113206660261.

48. Di Stefano A., Ricciardolo F.L.M., Caramori G. et al. Bronchial inflammation and bacterial load in stable COPD is associated with TLR4 overexpression. Eur. Respir. J. 2017; 49 (5): 1602006. DOI: 10.1183/13993003.02006-2016.

49. Dvoretsky L.I. [Elderly patient with chronic obstructive pulmonary disease in internist practice]. Rossiyskiy meditsinskiy zhurnal. 1999; (16): 788. Available at: https://www.rmj.ru/articles/geriatriya/Poghiloy_bolynoy_s_hronicheskim_obstruktivnym_zabolevaniem_legkih_v_praktike_internista/ (in Russian).

50. Kozlova A.N. [Morphofunctional characteristics of bronchial epithelium in human ontogenesis and under experimental conditions: PhD thesis]. Orenburg; 1997 (in Russian).

51. Pinkerton K.E., Barry B.E., O’Neil J.J. et al. Morphologic changes in the lung during the lifespan of Fischer 344 rats. Am. J. Anat. 1982; 164 (2): 155–174. DOI: 10.1002/aja.1001640206.

52. Margiana R., Liem I., Pawitan J. Microscopic study of the lungs of Sprague-Dawley rats from various ages of postnatal and aging periods. Online Journal of Biomedical Sciences. 2015; 15 (2): 74–82. DOI: 10.3844/ojbsci.2015.74.82.

53. Yang Y.H. Pulmonary alveoli and macrophages of rats: a study of aging changes by electron microscopy. Yonsei Med. J. 1968; 9 (1): 1–10. DOI: 10.3349/ymj.1968.9.1.1.

54. Furchgott R.F., Zawadzki J.V. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980; 288 (5789): 373–376. DOI: 10.1038/288373a0.

55. Barua R.S., Ambrose J.A., Srivastava S. et al. Reactive oxygen species are involved in smoking-induced dysfunction of nitric oxide biosynthesis and upregulation of endothelial nitric oxide synthase: an in vitro demonstration in human coronary artery endothelial cells. Circulation. 2003; 107 (18): 2342–2347. DOI: 10.1161/01.CIR.0000066691.52789.BE.

56. Kamasheva G.R., Sineglazova A.V., Arkhipov E.V. [Morphofunctional aspects of aging that determine the course of respiratory diseases in old and senile age]. Vestnik sovremennoy klinicheskoy meditsiny. 2022; 15 (2): 95–102. DOI: 10.20969/vskm.2022.15(2).95-102 (in Russian).

57. Schneider J.L., Rowe J.H., Garcia-de-Alba C. et al. The aging lung: physiology, disease, and immunity. Cell. 2021; 184 (8): 1990–2019. DOI: 10.1016/j.cell.2021.03.005.

58. Wong C.K., Smith C.A., Sakamoto K. et al. Aging impairs alveolar macrophage phagocytosis and increases influenza-induced mortality in mice. J. Immunol. 2017; 199 (3): 1060–1068. DOI: 10.4049/jimmunol.1700397.

59. Hearps A.C., Martin G.E., Angelovich T.A. et al. Aging is associated with chronic innate immune activation and dysregulation of monocyte phenotype and function. Aging Cell. 2012; 11 (5): 867–875. DOI: 10.1111/j.1474-9726.2012.00851.x.

60. Metcalf T.U., Cubas R.A., Ghneim K. et al. Global analyses revealed age-related alterations in innate immune responses after stimulation of pathogen recognition receptors. Aging Cell. 2015; 14 (3): 421–432. DOI: 10.1111/acel.12320.

61. Svartengren M., Falk R., Philipson K. Long-term clearance from small airways decreases with age. Eur. Respir. J. 2005; 26 (4): 609–615. DOI: 10.1183/09031936.05.00002105.

62. Malyavin A.G., Babak S.L., Gorbunova M.V. et al. [Clinical and pathomorphological parallels of chronic obstructive pulmonary disease and senile lung]. Doctor.Ru. 2013; 8 (86): 29–33. Available at: https://cyberleninka.ru/article/n/kliniko-patomorfologicheskieparalleli-hronicheskoy-obstruktivnoy-bolezni-legkih-i-senilnogo-legkogo (in Russian).

63. Brandenberger C., Mühlfeld C. Mechanisms of lung aging. Cell Tissue Res. 2017; 367 (3): 469–480. DOI: 10.1007/s00441-016-2511-x.

64. Woldhuis R.R., Heijink I.H., van den Berge M. et al. COPD-derived fibroblasts secrete higher levels of senescence-associated secretory phenotype proteins. Thorax. 2021; 76 (5): 508–511. DOI: 10.1136/thoraxjnl-2020-215114.

65. Taylor A.E., Finney-Hayward T.K., Quint J.K. et al. Defective macrophage phagocytosis of bacteria in COPD. Eur. Respir. J. 2010; 35(5): 1039–1047. DOI: 10.1183/09031936.00036709.

66. Averyanov A.V., Kogan E.A., Lesnyak V.N. et al. [Difficult to diagnose rare diffuse lung diseases: translation from English]. Moscow: Prakticheskaya meditsina; 2022: 46–74 (in Russian).

67. Avdeev S.N., Chikina S.Yu., Nagatkina O.V. [Idiopathic pulmonary fibrosis: a new international clinical guideline]. Pulmonologiya. 2019; 29 (5): 525–552. DOI: 10.18093/0869-0189-2019-29-5-525-552 (in Russian).

68. Yao C., Guan X., Carraro G. et al. Senescence of alveolar type 2 cells drives progressive pulmonary fibrosis. Am. J. Respir. Crit. Care Med. 2021; 203 (6): 707–717. DOI: 10.1164/rccm.202004-1274OC.

69. Sundaresan N.R., Bindu S., Pillai V.B. et al. SIRT3 blocks aging-associated tissue fibrosis in mice by deacetylating and activating glycogen synthase kinase 3β. Mol. Cell. Biol. 2015; 36 (5): 678–692. DOI: 10.1128/MCB.00586-15.

70. Smirnova M.S., Nekrasov A.A. [Pathogenesis, clinical presentation and diagnosis of idiopathic pulmonary fibrosis in the elderly]. Klinicheskaya gerontologiya. 2022; 28: (9–10): 24–29. DOI: 10.26347/1607-2499202209-10024-029 (in Russian).

71. Baumgartner K.B., Samet J.M., Stidley C.A. et al. Cigarette smoking: a risk factor for idiopathic pulmonary fibrosis. Am. J. Respir. Crit. Care Med. 1997; 155 (1): 242–248. DOI: 10.1164/ajrccm.155.1.9001319.

72. Wu Y., Goplen N.P., Sun J. Aging and respiratory viral infection: from acute morbidity to chronic sequelae. Cell Biosci. 2021; 11 (1): 112. DOI: 10.1186/s13578-021-00624-2.

73. Saliev T., Singh P.B. Targeting senescence: a review of senolytics and senomorphics in anti-aging interventions. Biomolecules. 2025; 15 (6): 860. DOI: 10.3390/biom15060860.

74. Ilyushchenko A.K., Machekhina L.V., Tkacheva O.N. et al. [Senolytic drugs: potential for use in clinical practice]. Problemy geronauki. 2023; (1): 7–14. DOI: 10.37586/2949-4745-1-2023-7-14 (in Russian).

75. Kim E.C., Kim J.R. Senotherapeutics: emerging strategy for healthy aging and age-related disease. BMB Rep. 2019; 52 (1): 47–55. DOI: 10.5483/BMBRep.2019.52.1.293.

76. Partridge L., Fuentealba M., Kennedy B.K. The quest to slow ageing through drug discovery. Nat. Rev. Drug Discov. 2020; 19 (8): 513–532. DOI: 10.1038/s41573-020-0067-7.

77. Zhang L., Pitcher L.E., Prahalad V. et al. Targeting cellular senescence with senotherapeutics: senolytics and senomorphics. FEBS J. 2022; 290 (5): 1362–1383. DOI: 10.1111/febs.16350.

78. Lagoumtzi S.M., Chondrogianni N. Senolytics and senomorphics: natural and synthetic therapeutics in the treatment of aging and chronic diseases. Free Radic. Biol. Med. 2021; 171: 169–190. DOI: 10.1016/j.freeradbiomed.2021.05.021.

79. Barzilai N.R. Targeting aging with metformin (TAME). Innov. Aging. 2017; 1 (Suppl. 1): 743. DOI: 10.1093/geroni/igx004.2691.