Aging and osteoarthritis. Chronic nonspecific inflammation as a link between aging and osteoarthritis (a review)


This paper presents a review on the processes underlying aging and the most common age-associated diseases. Special attention is given to the role of chronic nonspecific inflammation. Based on the literature data, aging and osteoarthritis (OA) were demonstrated to have the same basic molecular and cellular mechanisms, among which a significant role is played by general cascades of intracellular transcription, chronic nonspecific inflammation, and metabolic disorders. It is concluded that the process of normal aging is not a disease, but it makes the human body, particularly the musculoskeletal system, susceptible to ageassociated changes. A number of changes in the human body that accompany the aging process and play a certain role in the development and progress of OA are potentially reversible regardless of age (e.g., chronic nonspecific inflammation), and they can be considered as possible application points for the effective prevention and complex therapy of OA in elderly people.

This is a preview of subscription content, access via your institution.


  1. 1.

    Alekseeva, L.I., Chichasova, N.V., Benevolenskaya, L.I., et al., Implementation of combined preparation ARTRA for treatment of osteoarthrosis, Ter. Arkh., 2005, no. 11, pp. 69–75.

    Google Scholar 

  2. 2.

    Anisimov, V.N., Molekulyarnye i fiziologicheskie mekhanizmy stareniya (Molecular and Physiological Mechanisms of Aging), St. Petersburg: Nauka, 2008, vol. 1.

    Google Scholar 

  3. 3.

    Kishkun, A.V., Biologicheskii vozrast i starenie: vozmozhnosti opredeleniya i puti korrektsii: Rukovodstvo dlya vrachei (Biological Age and Aging: Methods of Determination and Correction, Manual for Physicians), Moscow: GEOTAR-Media, 2008.

    Google Scholar 

  4. 4.

    Lazebnik, L.B., Aging and polymorbidity, Consilium Med., 2005, vol. 7, no. 12, pp. 993–996.

    Google Scholar 

  5. 5.

    Mendel, O.I., Naumov, A.V., Vertkin, A.L., et al., Osteoarthrosis and cardiovascular diseases of elderly patients: clinical-pathogenetic relationships, Usp. Gerontol., 2010, vol. 23, no. 2, pp. 304–317.

    CAS  Google Scholar 

  6. 6.

    Concise Report on the World Population Situation in 2014, New York: UN Dep. Econ. Soc. Affairs, 2014.

  7. 7.

    Nasonova, V.A., Osteoarthrosis of elderly people as the urgent medical problem of 21 century, Consilium Med., 2003, vol. 5, no. 12, pp. 34–37.

    Google Scholar 

  8. 8.

    Aigner, T., Kim, H.A., and Roach, H.I., Apoptosis in osteoarthritis, Rheum. Dis. Clin. North. Am., 2004, vol. 30, no. 3, pp. 639–653.

    Article  PubMed  Google Scholar 

  9. 9.

    Altman, R.D., Criteria for classification of clinical osteoarthritis, J. Rheumatol., 1991, vol. 18, suppl. 27, pp. 10–12.

    Google Scholar 

  10. 10.

    Baylis, D., Bartlett, D.B., Patel, H.P., and Roberts, H.C., Understanding how we age: insights into inflammaging, Longevity Healthspan, 2013, vol. 2, no. 1, p. 8.

    Google Scholar 

  11. 11.

    Berenbaum, F., Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!), Osteoarthritis Cartilage, 2013, vol. 2, no. 1, pp. 16–21.

    Article  Google Scholar 

  12. 12.

    Bijlsma, J.W., Berenbaum, F., and Lafeber, F.P., Osteoarthritis: an update with relevance for clinical practice, Lancet, 2011, vol. 377, pp. 2115–2126.

    Article  PubMed  Google Scholar 

  13. 13.

    Blagojevic, M., Jinks, C., Jeffery, A., and Jordan, K.P., Risk factors for onset of osteoarthritis of the knee in older adults: a systematic review and meta-analysis, Osteoarthritis Cartilage, 2010, vol. 18, no. 1, pp. 24–33.

    Article  CAS  PubMed  Google Scholar 

  14. 14.

    Buckland-Wright, J.C., Lynch, J.A., and Macfarlane, D.G., Fractal signature analysis measures cancellous bone organization in macroradiograph of patients with knee osteoarthritis, Ann. Rheum. Dis., 1996, vol. 55, p. 749.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. 15.

    Burr, D.B., The importance of subchondral bone in the progression of osteoarthritis, J. Rheumatol., 2004, suppl. 70, pp. 77–80.

    Google Scholar 

  16. 16.

    Burr, D.B. and Radin, E.L., Microfractures and microcracks in subchondral bone: are they relevant to osteoarthrosis?, Rheum. Dis. Clin. North. Am., 2003, vol. 29, no. 4, pp. 675–685.

    Article  PubMed  Google Scholar 

  17. 17.

    Candore, G., Aquino, A., Balistreri, C.R., et al., Immune-inflammatory responses in successful and unsuccessful ageing, J. Gerontol., 2009, vol. 57, pp. 145–152.

    Google Scholar 

  18. 18.

    Cannizzo, E.S., Clement, C.C., Sahu, R., et al., Oxidative stress, inflammaging and immunosenescence, J. Proteomics, 2011, vol. 74, no. 11, pp. 2313–2323.

    Article  CAS  PubMed  Google Scholar 

  19. 19.

    Castaneda, S., Roman-Blas, J.A., Largo, R., and Herrero-Beaumont, G., Osteoarthritis: a progressive disease with changing phenotypes, Rheumatol. Oxford J., 2014, vol. 53, no. 1, pp. 1–3.

    Article  Google Scholar 

  20. 20.

    Centers for Disease Control and Prevention, Prevalence of disabilities and associated health conditions among adults—United States, 1999, Morbidity Mortal. Wkly. Rep., 2001, vol. 50, pp. 120–125.

    Google Scholar 

  21. 21.

    Chaganti, R.K. and Lane, N.E., Risk factors for incident osteoarthritis of the hip and knee, Curr. Rev. Musculoskelet. Med., 2011, vol. 4, pp. 99–104.

    Article  PubMed Central  PubMed  Google Scholar 

  22. 22.

    Chavakis, T., Bierhaus, A., and Nawroth, P.P., RAGE (receptor for advanced glycation end products): a central player in the inflammatory response, Microbes Infect., 2004, vol. 6, no. 13, pp. 1219–1225.

  23. 23.

    Fei, Ch., Bower, J., Demers, L.M., and Shi, X., Upstream signal transduction of NF-κB activation, Atlas Genet. Cytogenet. Oncol. Haematol., 2002, vol. 6, no. 2, pp. 94–96.

    Google Scholar 

  24. 24.

    DeGroot, J., Verzijl, N., Wenting-Van, Wijk, M.J., et al., Age-related decrease in susceptibility of human articular cartilage to matrix metalloproteinase-mediated degradation: the role of advanced glycation end products, Arthritis Rheumatol., 2001, vol. 44, no. 11, pp. 2562–2571.

  25. 25.

    Dehring, K.A., Roessler, B.J., and Morris, M.D., Correlating chemical changes in subchondral bone mineral due to aging or defective type II collagen by Raman spectroscopy, in Progress in Biomedical Optics and Imaging. Advanced Biomedical and Clinical Diagnostic Systems, San Jose, CA: Soc. Photogr. Instrum. Eng., 2007, 64301B.

    Google Scholar 

  26. 26.

    Ding, M., Microarchitectural adaptations in aging and osteoarthrotic subchondral bone issues, Acta Orthop., 2010, vol. 81, no. 340, suppl., pp. 1–53.

    Article  Google Scholar 

  27. 27.

    Felson, D.T., The epidemiology of knee osteoarthritis: results from the Framingham Osteoarthritis Study, Seminars Arthritis Rheumatol., 1990, vol. 20, suppl., pp. 42–50.

    Article  CAS  Google Scholar 

  28. 28.

    Forsyth, C.B., Cole, A., Murphy, G., et al., Increased matrix metalloproteinase-13 production with aging by human articular chondrocytes in response to catabolic stimuli, J. Gerontol., Ser. A, 2005, vol. 60, pp. 1118–1124.

    Article  Google Scholar 

  29. 29.

    Fortin, M., Bravo, G., Hudon, C., et al., Prevalence of multimorbidity among adults seen in family practice, Ann. Fam. Med., 2005, vol. 3, no. 3, pp. 223–228.

    Article  PubMed Central  PubMed  Google Scholar 

  30. 30.

    Franceschi, C. and Campisi, J., Chronic inflammation (inflammaging) and its potential contribution to ageassociated diseases, J. Gerontol., Ser. A, 2014, vol. 69, suppl. 1, pp. 4–9.

    Article  Google Scholar 

  31. 31.

    Franceschi, C., Capri, M., Monti, D., et al., Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans, Mech. Ageing Dev., 2007, vol. 128, no. 1, pp. 92–105.

    Article  CAS  PubMed  Google Scholar 

  32. 32.

    Giordano, R., Forno, D., Zinna, D., et al., Human ageing and the growth hormone/insulin-like growth factor-I (GH/IGF-I) Axis—the impact of growth factors on dementia, Open Endocrinol. J., 2012, vol. 6, suppl. 1, pp. 49–61.

    Article  CAS  Google Scholar 

  33. 33.

    Giunta, B., Fernandez, F., Nikolic, W.V., et al., Inflammaging as a prodrome to Alzheimer’s disease, J. Neuroinflammation, 2008, vol. 5, no. 51, pp. 1–15.

    Google Scholar 

  34. 34.

    Goto, M., Inflammaging (inflammation + aging): a driving force for human aging based on an evolutionarily antagonistic pleiotropy theory?, Biosci. Trends, 2008, vol. 2, no. 6, pp. 218–230.

    PubMed  Google Scholar 

  35. 35.

    Guerne, P.A., Blanco, F., Kaelin, A., et al., Growth factor responsiveness of human articular chondrocytes in aging and development, Arthritis Rheumatol., 1995, vol. 38, pp. 960–968.

    Article  CAS  Google Scholar 

  36. 36.

    Hügle, T., Geurts, J., Nüesch, C., et al., Aging and osteoarthritis: an inevitable encounter?, J. Aging Res., 2012. doi: 10.1155/2012/950192

    Google Scholar 

  37. 37.

    Hochberg, M.C., Mortality in osteoarthritis, Clin. Exp. Rheumatol., 2008, vol. 26, no. 5, suppl. 51, pp. 120–124.

    Google Scholar 

  38. 38.

    Howcroft, T.K., Campisi, J., Louis, G.B., et al., The role of inflammation in age-related disease, Aging (Albany, NY), 2013, vol. 5, no. 1, pp. 84–93.

    CAS  Google Scholar 

  39. 39.

    Karsdal, M.A., Sondergaard, B.C., Arnold, M., and Christiansen, C., Calcitonin affects both bone and cartilage: a dual action treatment for osteoarthritis?, Ann. N.Y. Acad. Sci., 2007, vol. 1117, pp. 181–195.

    Article  CAS  PubMed  Google Scholar 

  40. 40.

    Khatami, M., Inflammation, aging and cancer: friend or foe?, in Inflammation, Chronic Diseases and Cancer—Cell and Molecular Biology, Immunology and Clinical Bases, Khatami, M., Ed., InTech, 2012.

    Google Scholar 

  41. 41.

    Kim, K.S., Seu, Y.B., Baek, S.H., et al., Induction of cellular senescence by insulin-like growth factor binding protein-5 through a p53-dependent mechanism, Mol. Biol. Cell., 2007, vol. 18, no. 11, pp. 4543–4552.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  42. 42.

    Krabbe, K.S., Pedersen, M., and Bruunsgaard, H., Inflammatory mediators in the elderly, Exp. Gerontol., 2004, vol. 39, no. 5, pp. 687–699.

    Article  CAS  PubMed  Google Scholar 

  43. 43.

    Kühn, K., D’Lima, D.D., Hashimoto, S., and Lotz, M., Cell death in cartilage, Osteoarthritis Cartilage, 2004, vol. 12, no. 1, pp. 1–16.

    Article  PubMed  Google Scholar 

  44. 44.

    Kuettner, K.E. and Goldberg, V.M., in Workshop “Osteoarthritic Disorders,” Monterey, California, 1994, Acad. Orthop. Surg. Symp. Ser., Rosemont, IL, 1995, pp. 27–45.

    Google Scholar 

  45. 45.

    Lajeunesse, D., Massicotte, F., Pelletier, J.P., and Martel-Pelletier, J., Subchondral bone sclerosis in osteoarthritis: not just an innocent bystander, Mod. Rheumatol., 2003, vol. 13, pp. 7–14.

    Article  CAS  PubMed  Google Scholar 

  46. 46.

    Lawrence, J.S., Bremner, J.M., and Bier, F., Osteoarthrosis: prevalence in population and relationship between symptoms and X-ray changes, Ann. Reum. Dis., 1966, vol. 25, no. 1, pp. 1–24.

    Article  CAS  Google Scholar 

  47. 47.

    Loeser, R.F., Aging cartilage and osteoarthritis cartilage: difference and shared mechanisms, in Osteoarthritis: A Companion to Rheumatology, Sharma, L. and Berenbaum, F., Eds., Philadelphia: Mosby, 2007, pp. 77–84.

    Google Scholar 

  48. 48.

    Loeser, R.F., Aging and osteoarthritis: the role of chondrocyte senescence and aging changes in the cartilage matrix, Osteoarthritis Cartilage, 2009, vol. 17, no. 8, pp. 971–979.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  49. 49.

    Loeser, R.F., Age-related changes in the musculoskeletal system and the development of osteoarthritis, Clin. Geriatr. Med., 2010, vol. 26, no. 3, pp. 371–386.

    Article  PubMed Central  PubMed  Google Scholar 

  50. 50.

    Luevano-Contreras, C. and Chapman-Novakofski, K., Dietary advanced glycation end products and aging, Nutrients, 2010, vol. 2, no. 12, pp. 1247–1265.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  51. 51.

    Malnick, S.D. and Knobler, H., The medical complications of obesity, Int. J. Med., 2006, vol. 99, no. 9, pp. 565–567.

    CAS  Google Scholar 

  52. 52.

    Martin, J.A., Klingelhutz, A.J., Moussavi-Harami, F., and Buckwalter, J.A., Effects of oxidative damage and telomerase activity on human articular cartilage chondrocyte senescence, J. Gerontol., A, 2004, vol. 59, no. 4, pp. 324–337.

    Article  Google Scholar 

  53. 53.

    Massicote, F., Lajeunesse, D., Benderdour, M., et al., Can altered production of interleukin 1-b, interleukin-6, transforming growth factor-beta and prostaglandin E2 by isolated human subchondral osteoblasts identify two subgroup of osteoarthritic patients?, Osteoarthritis Cartilage, 2002, vol. 10, no. 6, pp. 491–500.

    Article  Google Scholar 

  54. 54.

    Narici, M.V., Maffulli, N., and Maganaris, C.N., Ageing of human muscles and tendons, Disabil. Rehabil., 2008, vol. 30, nos. 20–22, pp. 1548–1554.

    Article  PubMed  Google Scholar 

  55. 55.

    Nüesch, E., Dieppe, P., Reichenbach, S., et al., All cause and disease specific mortality in patients with knee or hip osteoarthritis: population based cohort study, Br. Med. J., 2011, vol. 342, no. 7798, art. ID1165, pp. 638–641.

    Google Scholar 

  56. 56.

    Oliveria, S.A., Felson, D.T., Reed, J.I., et al., Incidence of symptomatic hand, hip, and knee osteoarthritis among patients in a health maintenance organization, Arthritis Rheumatol., 1995, vol. 38, no. 8, pp. 1134–1141.

    Article  CAS  Google Scholar 

  57. 57.

    Ott, C., Jacobs, K., Haucke, E., et al., Role of advanced glycation end products in cellular signaling, Redox. Biol., 2014, vol. 2, pp. 411–429.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  58. 58.

    Parsch, D., Brummendorf, T.H., Richter, W., and Fellenberg, J., Replicative aging of human articular chondrocytes during ex vivo expansion, Arthritis Rheumatol., 2002, vol. 46, pp. 2911–2916.

    Article  CAS  Google Scholar 

  59. 59.

    Pereira, D., Peleteiro, B., Araujo, J., et al., The effect of osteoarthritis definition on prevalence and incidence estimates: a systematic review, Osteoarthritis Cartilage, 2011, vol. 19, pp. 1270–1285.

    Article  CAS  PubMed  Google Scholar 

  60. 60.

    Roos, H., Adalberth, T., Dahlberg, L., and Lohmander, L.S., Osteoarthritis of the knee after injury to anterior cruciate ligament or meniscus: the influence of time and age, Osteoarthritis Cartilage, 1995, vol. 3, no. 4, pp. 261–267.

    Article  CAS  PubMed  Google Scholar 

  61. 61.

    Saltman, D.C., Sayer, G.P., and Whicker, S.D., Comorbidity in general practice, Postgrad. Med. J., 2005, vol. 81, pp. 474–480.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  62. 62.

    Sandell, L.J. and Aigner, T., Articular cartilage and changes in arthritis. An introduction: cell biology of osteoarthritis, Arthritis Res. Ther., 2001, vol. 3, suppl. 2, pp. 107–113.

    Article  CAS  Google Scholar 

  63. 63.

    Sarkar, F.H., Li, Y., Wang, Z., and Kong, D., NFkappa B signaling pathway and its therapeutic implications in human diseases, Int. Rev. Immunol., 2008, vol. 27, no. 5, pp. 293–319.

    Article  CAS  PubMed  Google Scholar 

  64. 64.

    Saudek, D.M. and Kay, J., Advanced glycation end products and osteoarthritis, Curr. Rheum. Rep., 2003, vol. 5, no. 1, pp. 33–40.

    Article  Google Scholar 

  65. 65.

    Sellam, J. and Berenbaum, F., The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis, Nat. Rev. Rheumatol., 2010, vol. 6, no. 11, pp. 625–635.

    Article  CAS  PubMed  Google Scholar 

  66. 66.

    Steenvoorden, M.M., Huizinga, T.W., Verzijl, N., et al., Activation of receptor for advanced glycation end products in osteoarthritis leads to increased stimulation of chondrocytes and synoviocytes, Arthritis Rheumatol., 2006, vol. 54, no. 1, pp. 253–263.

    Article  CAS  Google Scholar 

  67. 67.

    Sturmer, T., Brenner, H., Koenig, W., et al., Severity and extent of osteoarthritis and low grade systemic inflammation as assessed by high sensitivity C reactive protein, Ann. Rheum. Dis., 2004, vol. 63, suppl. 2, pp. 200–205.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  68. 68.

    Suri, P., Morgenroth, D.C., and Hunter, D.J., Epidemiology of osteoarthritis and associated comorbidities, Phys. Med. Rehabil., 2012, vol. 4, suppl. 5, pp. 10–19.

    Google Scholar 

  69. 69.

    Tedgui, A. and Mallat, Z., Cytokines in atherosclerosis: pathogenic and regulatory pathways, Physiol. Rev., 2006, vol. 86, no. 2, pp. 515–581.

    Article  CAS  PubMed  Google Scholar 

  70. 70.

    Tilstra, J.S., Robinson, A.R., Wang, J., et al., NF-kB inhibition delays DNA damage-induced senescence and aging in mice, J. Clin. Invest., 2012, vol. 122, no. 7, pp. 2601–2612.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  71. 71.

    Turkiewicz, A., Petersson, I.F., Björk, G., et al., Current and future impact of osteoarthritis on health care: a population-based study with projections to year 2032, Osteoarthritis Cartilage, 2014, vol. 22, suppl. 11, pp. 1826–1832.

    Article  CAS  PubMed  Google Scholar 

  72. 72.

    van Beuningen, H.M., van der Kraan, P.M., Arntz, O.J., and van den Berg, W.B., Transforming growth factorbeta 1 stimulated articular chondrocyte proteoglycan synthesis and induces osteophyte formation in the murine knee joint, Lab. Invest., 1994, vol. 71, p. 279.

    CAS  PubMed  Google Scholar 

  73. 73.

    Verzijl, N., Bank, R.A., TeKoppele, J.M., and DeGroot, J., Ageing and osteoarthritis: a different perspective, Curr. Opin. Rheumatol., 2003, vol. 15, pp. 616–622.

    Article  PubMed  Google Scholar 

  74. 74.

    Westacott, C I., Webb, G.R., Warnock, M.G., et al., Alteration of cartilage metabolism by cells from osteoarthritic bone, Arthritis Rheumatol., 1997, vol. 40, pp. 1282–1289.

    Article  CAS  Google Scholar 

  75. 75.

    Wolff, J., Starfield, B., and Anderson, G., Prevalence, expenditures, and complications of multiple chronic conditions in the elderly, Arch. Int. Med., 2002, vol. 162, pp. 2269–2276.

    Article  Google Scholar 

  76. 76.

    Yamada, K., Healey, R., Amiel, D., et al., Subchondral bone of the human knee joint in aging and osteoarthritis, Osteoarthritis Cartilage, 2002, vol. 10, no. 5, pp. 360–369.

    Article  CAS  PubMed  Google Scholar 

  77. 77.

    Zhang, W., Likhodii, S., Zhang, Y., et al., Classification of osteoarthritis phenotypes by metabolomics analysis, Br. Med. J., 2014, vol. 19, no. 4, p. 6286.

    Google Scholar 

Download references

Author information



Corresponding author

Correspondence to O. I. Mendel.

Additional information

Original Russian Text © O.I. Mendel, L.V. Luchihina, W. Mendel, 2015, published in Uspekhi Gerontologii, 2015, Vol. 28, No. 2, pp. 274–283.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Mendel, O.I., Luchihina, L.V. & Mendel, W. Aging and osteoarthritis. Chronic nonspecific inflammation as a link between aging and osteoarthritis (a review). Adv Gerontol 5, 252–260 (2015).

Download citation


  • aging
  • osteoarthritis
  • articular cartilage
  • inflammation
  • immunosenescence
  • inflammaging
  • cytokines
  • oxidative stress
  • metabolic disturbances