Aging, immune system, and physical activity: A review of recent studies

Document Type : Review Articles


1 Associate Prof, Department of Physical Education, Faculty of Letters and Humanities, Vali-e-Asr University, Rafsanjan, Iran.

2 PhD Student in Exercise Physiology, Faculty of Humanities, Tarbiat Modares University, Tehran, Iran.


The immune system is one of the main defenders of human health. The immune system can fight off viruses in the body and kill them. Therefore, keeping the components of the immune system healthy is very important. With age, the immune system ages, and its function decreases. This decline in immune function can easily lead to viral infections in the elderly. Evidence is accumulated that the best solution to maintain and enhance the immune system in the elderly is physical activity. Regular physical activity can lead to healthy aging of the immune system. Therefore, in this review study, we have discussed the changes in the immune system during aging and physical activity suggestions for healthy aging of the immune system. Finally, future research needs are reported.

What is already known on this subject?

With age, the function of the immune system decreases, and this can increase the severity of the disease in the elderly and lead to death in most cases.


What this study adds?

Moderate intensity training (aerobic and resistance training) under the supervision of an expert can lead to the improvement of the body's immune system and reduce the severity of the disease in the elderly.


Main Subjects

Abd El-Kader, S. M., & Al-Jiffri, O. H. (2020). Aerobic exercise affects sleep, psychological wellbeing and immune system parameters among subjects with chronic primary insomnia. African health sciences, 20(4), 1761-1769. doi:
Abodonya, A. M., Abdelbasset, W. K., Awad, E. A., Elalfy, I. E., Salem, H. A., & Elsayed, S. H. (2021). Inspiratory muscle training for recovered COVID-19 patients after weaning from mechanical ventilation: A pilot control clinical study. Medicine, 100(13). doi:
Agha-Alinejad, H., Ahmadi Hekmatikar, A. H., Ruhee, R. T., Shamsi, M. M., Rahmati, M., Khoramipour, K., & Suzuki, K. (2022). A Guide to Different Intensities of Exercise, Vaccination, and Sports Nutrition in the Course of Preparing Elite Athletes for the Management of Upper Respiratory Infections during the COVID-19 Pandemic: A Narrative Review. International Journal of Environmental Research and Public Health, 19(3), 1888. doi:
Aguiar, S. S., Sousa, C. V., Deus, L. A., Rosa, T. S., Sales, M. M., Neves, R. V. P., . . . Simões, H. G. (2020). Oxidative stress, inflammatory cytokines and body composition of master athletes: the interplay. Experimental gerontology, 130, 110806. doi:
Ahmadi Hekmatikar, A., Haghshenas, R., & Mohammad Sadeghipor, A. (2019). The effect of carbohydrate supplementation and pure water on interleukin 10, glucose and hematological indexes in male football players. Sport Physiology & Management Investigations, 11(4), 135-145.
Ahmadi Hekmatikar, A. H., R.; Mohammad Sadeghipor, A. . (2019). The effect of carbohydrate supplementation and pure water on interleukin 10, glucose and hematologicalindexes in male football players. Sport Physiol. Manag. Investig. 2019, 11, 135–145.
Akha, A. A. S., & Miller, R. A. (2005). Signal transduction in the aging immune system. Current opinion in immunology, 17(5), 486-491. doi:
Aktuğ, Z. B., İri, R., & Demir, N. A. (2020). COVID-19 immune system and exercise: COVID-19 immün system ve egzersiz. Journal of Human Sciences, 17(2), 513-520. doi:
Allbutt, C. (1924). Hippocrates-Hippocrates. With English Translation by WHS Jones, St. Catherine's College, Cambridge (Loeb Classical Library.) Vol. II. Pp. lvi+ 336: London: Heinemann; New York: GP Putnam's Sons, 1923.-Hippocrates and his Successors in Relation to the Philosophy of their Time. By RO Moon, MD, FRCP The Fitzpatrick Lectures, RCP, 1921–22. London: Longmans, 1923. 6s. The Classical Review, 38(7-8), 175-177.
Anastasilakis, A. D., Polyzos, S. A., Saridakis, Z. G., Kynigopoulos, G., Skouvaklidou, E. C., Molyvas, D., . . . Siopi, A. (2014). Circulating irisin in healthy, young individuals: day-night rhythm, effects of food intake and exercise, and associations with gender, physical activity, diet, and body composition. The Journal of Clinical Endocrinology & Metabolism, 99(9), 3247-3255. doi:
Baker, F. L., & Simpson, R. J. (2021). Exercise to Support Optimal Immune Function. ACSM's Health & Fitness Journal, 25(1), 5-8. doi:
Bartleson, J. M., Radenkovic, D., Covarrubias, A. J., Furman, D., Winer, D. A., & Verdin, E. (2021). SARS-CoV-2, COVID-19 and the aging immune system. Nature Aging, 1(9), 769-782. doi:
Betschart, M., Rezek, S., Unger, I., Beyer, S., Gisi, D., Shannon, H., & Sieber, C. (2021). Feasibility of an Outpatient Training Program after COVID-19. International Journal of Environmental Research and Public Health, 18(8), 3978. doi:
Booth, F. W., Roberts, C. K., & Laye, M. J. (2012). Lack of exercise is a major cause of chronic diseases. Comprehensive physiology, 2(2), 1143. doi:
Brolinson, P. G., & Elliott, D. (2007). Exercise and the immune system. Clinics in sports medicine, 26(3), 311-319. doi:
Bulló, M., Casas-Agustench, P., Amigó-Correig, P., Aranceta, J., & Salas-Salvadó, J. (2007). Inflammation, obesity and comorbidities: the role of diet. Public health nutrition, 10(10A), 1164-1172. doi:
Campbell, J. P., & Turner, J. E. (2018). Debunking the Myth of Exercise-Induced Immune Suppression: Redefining the Impact of Exercise on Immunological Health Across the Lifespan. Frontiers in immunology, 9, 648. doi:
Campos, M. V. A., & Miguel, H. (2020). Elastic resistance training: resistance exercise alternative in the home environment during Covid-19 pandemic. InterAmerican Journal of Medicine and Health, 3.
Cannon, J. G. (2000). Inflammatory Cytokines in Nonpathological States. News Physiol Sci, 15, 298-303. doi:
Caussy, C., Wallet, F., Laville, M., & Disse, E. (2020). Obesity is associated with severe forms of COVID‐19. Obesity, 28(7), 1175-1175. PMID: 32959515; PMCID: PMC7536951.
Chaussabel, D., Pascual, V., & Banchereau, J. (2010). Assessing the human immune system through blood transcriptomics. BMC biology, 8(1), 1-14. doi:
Chowdhury, M. A., Hossain, N., Kashem, M. A., Shahid, M. A., & Alam, A. (2020). Immune response in COVID-19: A review. Journal of Infection and Public Health, 13(11), 1619-1629. doi:
Córdova Martínez, A., Pérez-Valdecantos, D., Caballero-García, A., Sarabia, J. M., & Roche, E. (2021). Effect of exercise in the recovery process after the inflammation process caused by coronavirus. 6;127(11):1437-1455. doi:
da Silveira, M. P., da Silva Fagundes, K. K., Bizuti, M. R., Starck, É., Rossi, R. C., & de Resende e Silva, D. T. (2021). Physical exercise as a tool to help the immune system against COVID-19: an integrative review of the current literature. Clinical and experimental medicine, 21(1), 15-28. doi:
do Brito Valente, A. F., Jaspers, R. T., & Wüst, R. C. (2021). Regular physical exercise mediates the immune response in atherosclerosis. Exercise immunology review, 27, 42-53. doi:
Dobner, J., & Kaser, S. (2018). Body mass index and the risk of infection - from underweight to obesity. Clinical Microbiology and Infection, 24(1), 24-28.
Domin, R., Dadej, D., Pytka, M., Zybek-Kocik, A., Ruchała, M., & Guzik, P. (2021). Effect of Various Exercise Regimens on Selected Exercise-Induced Cytokines in Healthy People. International Journal of Environmental Research and Public Health, 18(3), 1261. doi:
Eichner, E. R. (2020). Exercise Immunology Reconsidered. Current sports medicine reports, 19(9), 341-342. doi:
Farhani, F., Shahrbanian, S., Auais, M., Hekmatikar, A. H. A., & Suzuki, K. (2022). Effects of aerobic training on brain plasticity in patients with mild cognitive impairment: a systematic review of randomized controlled trials. Brain Sciences, 12(6), 732. doi:
Ferrucci, L., & Fabbri, E. (2018). Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty. Nature Reviews Cardiology, 15(9), 505-522. doi:
Fonseca, T. R., Mendes, T. T., Ramos, G. P., Cabido, C. E. T., Morandi, R. F., Ferraz, F. O., . . . Teixeira, M. M. (2021). Aerobic Training Modulates the Increase in Plasma Concentrations of Cytokines in response to a Session of Exercise. Journal of Environmental and Public Health, 2021, 1304139. doi:
Gleeson, M., McDonald, W., Cripps, A., Pyne, D., Clancy, R., & Fricker, P. (1995). The effect on immunity of long‐term intensive training in elite swimmers. Clinical & Experimental Immunology, 102(1), 210-216. doi:
Gruver, A., Hudson, L., & Sempowski, G. (2007). Immunosenescence of ageing. The Journal of Pathology: A Journal of the Pathological Society of Great Britain and Ireland, 211(2), 144-156. doi:
Hall, G., Laddu, D. R., Phillips, S. A., Lavie, C. J., & Arena, R. (2021). A tale of two pandemics: How will COVID-19 and global trends in physical inactivity and sedentary behavior affect one another? Progress in cardiovascular diseases, 64, 108. doi:
Hekmatikar, A. H. A., Shamsi, M. M., Ashkazari, Z. S. Z., & Suzuki, K. (2021). Exercise in an overweight patient with COVID-19: a case study. International Journal of Environmental Research and Public Health, 18(11), 5882. doi:
Helmark, I. C., Mikkelsen, U. R., Børglum, J., Rothe, A., Petersen, M. C., Andersen, O., . . . Kjaer, M. (2010). Exercise increases interleukin-10 levels both intraarticularly and peri-synovially in patients with knee osteoarthritis: a randomized controlled trial. Arthritis research & therapy, 12(4), 1-11. doi:
Jee, Y.-S. (2021). Acquired immunity and moderate physical exercise: 5th series of scientific evidence. Journal of exercise rehabilitation, 17(1), 2.
Jesus, I., Vanhee, V., Deramaudt, T. B., & Bonay, M. (2021). Promising effects of exercise on the cardiovascular, metabolic and immune system during COVID-19 period. Journal of Human Hypertension, 35(1), 1-3. doi:
Khoramipour, K., Basereh, A., Hekmatikar, A. A., Castell, L., Ruhee, R. T., & Suzuki, K. (2021). Physical activity and nutrition guidelines to help with the fight against COVID-19. Journal of Sports Sciences, 39(1), 101-107. doi:
Krishnamurty, A. T., & Turley, S. J. (2020). Lymph node stromal cells: cartographers of the immune system. Nat Immunol, 21(4), 369-380. doi:
Kumar, S., Nyodu, R., Maurya, V. K., & Saxena, S. K. (2020). Host immune response and immunobiology of human SARS-CoV-2 infection. In Coronavirus Disease 2019 (COVID-19) (pp. 43-53). Springer. doi:
Laine, M., Eriksson, J., Kujala, U., Kaprio, J., Loo, B. M., Sundvall, J., . . . Sarna, S. (2016). Former male elite athletes have better metabolic health in late life than their controls. Scandinavian Journal of Medicine & Science in Sports, 26(3), 284-290. doi:
Lehmann, M., Mann, H., Gastmann, U., Keul, J., Vetter, D., Steinacker, J. M., & Häussinger, D. (1996). Unaccustomed high-mileage vs intensity training-related changes in performance and serum amino acid levels. International journal of sports medicine, 17(03), 187-192. doi:
Li, X., Ploner, A., Wang, Y., Zhan, Y., Pedersen, N. L., Magnusson, P. K., . . . Hägg, S. (2021). Clinical biomarkers and associations with healthspan and lifespan: evidence from observational and genetic data. EBioMedicine, 66, 103318. doi:
Linton, P. J., & Dorshkind, K. (2004). Age-related changes in lymphocyte development and function. Nature immunology, 5(2), 133-139. doi:
Mackinnon, L. T., Hooper, S. L., Jones, S., Gordon, R. D., & Bachmann, A. W. (1997). Hormonal, immunological, and hematological responses to intensified training in elite swimmers. Med Sci Sports Exerc, 29(12), 1637-1645. doi:
Mahdieh, M. S., Maryam, J., Bita, B., Neda, F., Motahare, M., Mahboobeh, B., . . . Kalani Behrooz, S. (2021). A pilot study on the relationship between Lactobacillus, Bifidibactrium counts and inflammatory factors following exercise training. Archives of Physiology and Biochemistry, 1-10. doi:
Méndez, C. (1960). Book of bodily exercise. Licht.
Miles, M. P. (2009). Moving Toward Solid Ground on Exercise and Immune Defense Against Viral Infection. Exercise and sport sciences reviews, 37(4), 155. doi:
Moderbacher, C. R., Ramirez, S. I., Dan, J. M., Grifoni, A., Hastie, K. M., Weiskopf, D., . . . Choi, J. (2020). Antigen-specific adaptive immunity to SARS-CoV-2 in acute COVID-19 and associations with age and disease severity. Cell, 183(4), 996-1012. e1019. doi:
Moghadam, M. T., Taati, B., Paydar Ardakani, S. M., & Suzuki, K. (2021). Ramadan Fasting During the COVID-19 Pandemic; Observance of Health, Nutrition and Exercise Criteria for Improving the Immune System [Review]. Frontiers in nutrition, 7(349). doi:
Nathan, C., & Sporn, M. (1991). Cytokines in context. Journal of Cell Biology, 113(5), 981-986.
Nieman, D. C. (1998). Exercise and resistance to infection. Canadian journal of physiology and pharmacology, 76(5), 573-580. doi:
Nieman, D. C., & Pence, B. D. (2020). Exercise immunology: future directions. Journal of Sport and Health Science, 9(5), 432-445. doi:
Nieman, D. C., & Wentz, L. M. (2019). The compelling link between physical activity and the body's defense system. Journal of Sport and Health Science, 8(3), 201-217. doi:
Oh, S., Chun, S., Hwang, S., Kim, J., Cho, Y., Lee, J., . . . Choi, S.-W. (2021). Vitamin D and Exercise Are Major Determinants of Natural Killer Cell Activity, Which Is Age- and Gender-Specific [Original Research]. Frontiers in Immunology, 12(2488). doi:
Papp, G., Szabó, K., Jámbor, I., Mile, M., Berki, A. R., Arany, A. C., . . . Balogh, L. (2021). Regular Exercise May Restore Certain Age-Related Alterations of Adaptive Immunity and Rebalance Immune Regulation [Original Research]. Frontiers in Immunology, 12(1279). doi:
Pedersen, B. K., & Saltin, B. (2015). Exercise as medicine–evidence for prescribing exercise as therapy in 26 different chronic diseases. Scand J Med Sci Sports, 25, 1-72. doi:
Perrotta, F., Corbi, G., Mazzeo, G., Boccia, M., Aronne, L., D’Agnano, V., . . . Bianco, A. (2020). COVID-19 and the elderly: insights into pathogenesis and clinical decision-making. Aging clinical and experimental research, 1-10. doi:
Pi-Sunyer, X. (2009). The medical risks of obesity. Postgraduate medicine, 121(6), 21-33.
Piquet, V., Luczak, C., Seiler, F., Monaury, J., Martini, A., Ward, A. B., . . . Chambard, L. (2021a). Do patients with Covid-19 benefit from rehabilitation? Functional outcomes of the first 100 patients in a Covid-19 rehabilitation unit. Archives of Physical Medicine and Rehabilitation, 102(6), 1067-1074. doi:
Piquet, V., Luczak, C., Seiler, F., Monaury, J., Martini, A., Ward, A. B., . . . Chambard, L. (2021b). Do Patients with Covid-19 Benefit from Rehabilitation? Functional outcomes of the first 100 patients in a Covid-19 rehabilitation unit. Archives of physical medicine and rehabilitation. doi:
Quick, E. D., Leser, J. S., Clarke, P., & Tyler, K. L. (2014). Activation of intrinsic immune responses and microglial phagocytosis in an ex vivo spinal cord slice culture model of West Nile virus infection. Journal of virology, 88(22), 13005-13014. doi:
Rahayu, U. B., Rahman, F., Alis Setiyadi, N., & Azizan, A. (2021). Exercise and Physical Health in Survivors of COVID-19: A scoping review. Journal of Medicinal and Chemical Sciences, 4(2), 154-162. doi:
Rezaei, S., Shamsi, M. M., Mahdavi, M., Jamali, A., Prestes, J., Tibana, R. A., . . . Voltarelli, F. A. (2017). Endurance exercise training decreased serum levels of surfactant protein D and improved aerobic fitness of obese women with type-2 diabetes. Diabetology & metabolic syndrome, 9(1), 1-8.
Rouse, B. T., & Sehrawat, S. (2010). Immunity and immunopathology to viruses: what decides the outcome? Nature Reviews Immunology, 10(7), 514-526. doi:
Rykova, M. P., Antropova, E. N., Popov, D. V., Vinogradova, O. L., & Larina, I. M. (2008). [The activation processes of the immune system during low intensity exercise without relaxation]. Ross Fiziol Zh Im I M Sechenova, 94(2), 212-219.
Saçma, M., & Geiger, H. (2021). Exercise generates immune cells in bone. In: Nature Publishing Group.
Sadighi Akha, A. A. (2018). Aging and the immune system: An overview. Journal of Immunological Methods, 463, 21-26. doi:
Scartoni, F. R., Sant’Ana, L. d. O., Murillo-Rodriguez, E., Yamamoto, T., Imperatori, C., Budde, H., . . . Machado, S. (2020). Physical Exercise and Immune System in the Elderly: Implications and Importance in COVID-19 Pandemic Period [Mini Review]. Frontiers in Psychology, 11(3215). doi:
Scheffer, D. d. L., & Latini, A. (2020). Exercise-induced immune system response: Anti-inflammatory status on peripheral and central organs. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1866(10), 165823. doi:
Scudiero, O., Lombardo, B., Brancaccio, M., Mennitti, C., Cesaro, A., Fimiani, F., . . . Frisso, G. (2021). Exercise, Immune System, Nutrition, Respiratory and Cardiovascular Diseases during COVID-19: A Complex Combination. International Journal of Environmental Research and Public Health, 18(3), 904. doi:
Sellami, M., Gasmi, M., Denham, J., Hayes, L. D., Stratton, D., Padulo, J., & Bragazzi, N. (2018). Effects of acute and chronic exercise on immunological parameters in the elderly aged: can physical activity counteract the effects of aging? Frontiers in Immunology, 9, 2187. doi:
Shang, J., Ye, G., Shi, K., Wan, Y., Luo, C., Aihara, H., . . . Li, F. (2020). Structural basis of receptor recognition by SARS-CoV-2. Nature, 581(7807), 221-224. doi:
Shaw, A. C., Goldstein, D. R., & Montgomery, R. R. (2013). Age-dependent dysregulation of innate immunity. Nature Reviews Immunology, 13(12), 875-887. doi:
Sheikholeslami, S., Ghanbarian, A., & Azizi, F. (2018). The impact of physical activity on non-communicable diseases: Findings from 20 years of the Tehran Lipid and Glucose Study. International journal of endocrinology and metabolism, 16(4 Suppl).
Simpson, R. J., Campbell, J. P., Gleeson, M., Krüger, K., Nieman, D. C., Pyne, D. B., . . . Walsh, N. P. (2020). Can exercise affect immune function to increase susceptibility to infection? Exercise immunology review, 26, 8-22.
Simpson, R. J., Lowder, T. W., Spielmann, G., Bigley, A. B., LaVoy, E. C., & Kunz, H. (2012). Exercise and the aging immune system. Ageing Res Rev, 11(3), 404-420. doi:
Simpson, R. J., & Pawelec, G. (2021). Is mechanical loading essential for exercise to preserve the aging immune system? Immunity & Ageing, 18(1), 26. doi:
Smith, J. A. (1994). Neutrophils, host defense, and inflammation: a double‐edged sword. Journal of leukocyte biology, 56(6), 672-686.
Suzuki, K. (2019). Characterization of exercise-induced cytokine release, the impacts on the body, the mechanisms and modulations. Int. J. Sports Exerc. Med, 5, 1-13.
Suzuki, K. (2019). Chronic inflammation as an immunological abnormality and effectiveness of exercise. Biomolecules, 9(6), 223.
Suzuki, K., & Hayashida, H. (2021). Effect of exercise intensity on cell-mediated immunity. Sports, 9(1), 8.
Suzuki, K., Hekmatikar, A. H. A., Jalalian, S., Abbasi, S., Ahmadi, E., Kazemi, A., . . . Khoramipour, K. (2022). The Potential of Exerkines in Women’s COVID-19: A New Idea for a Better and More Accurate Understanding of the Mechanisms behind Physical Exercise. International Journal of Environmental Research and Public Health, 19(23), 15645.
Tarazona, R., DelaRosa, O., Alonso, C., Ostos, B., Espejo, J. n., Peña, J., & Solana, R. (2001). Increased expression of NK cell markers on T lymphocytes in aging and chronic activation of the immune system reflects the accumulation of effector/senescent T cells. Mechanisms of ageing and development, 121(1-3), 77-88.
Tayebi, S. M., Hekmatikar, A. A., Ghanbari-Niaki, A., & Fathi, R. (2020). Ghrelin behavior in exercise and training. J Med. Sci, 27, 85-111.
Uddin, R., Lee, E.-Y., Khan, S. R., Tremblay, M. S., & Khan, A. (2020). Clustering of lifestyle risk factors for non-communicable diseases in 304,779 adolescents from 89 countries: A global perspective. Preventive medicine, 131, 105955.
Valizadeh, R., Karampour, S., Saiiari, A., & Sadeghi, S. (2021). The effect of one bout submaximal endurance exercise on the innate and adaptive immune responses of hypertensive patients. The Journal of sports medicine and physical fitness. doi:
Velavan, T. P., & Meyer, C. G. (2020). The COVID‐19 epidemic. Tropical medicine & international health, 25(3), 278.
Walsh, N. P., Gleeson, M., Shephard, R. J., Gleeson, M., Woods, J. A., Bishop, N., . . . Hoffman-Goete, L. (2011). Position statement part one: immune function and exercise.
Walsh, N. P., Gleeson, M., Shephard, R. J., Gleeson, M., Woods, J. A., Bishop, N. C., . . . Simon, P. (2011). Position statement. Part one: Immune function and exercise. Exerc Immunol Rev, 17, 6-63.
Wan, Y., Shang, J., Graham, R., Baric, R. S., & Li, F. (2020). Receptor recognition by the novel coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS coronavirus. Journal of virology, 94(7).
Wang, J., Liu, S., Li, G., & Xiao, J. (2020). Exercise Regulates the Immune. Physical Exercise for Human Health, 1228, 395.
Wang, Q., Zhang, Y., Wu, L., Niu, S., Song, C., Zhang, Z., . . . Yuen, K.-Y. (2020). Structural and functional basis of SARS-CoV-2 entry by using human ACE2. Cell, 181(4), 894-904. e899.
Weng, N.-p. (2006). Aging of the Immune System: How Much Can the Adaptive Immune System Adapt? Immunity, 24(5), 495-499. doi:
Yıldızgören, M. T. (2020). How Exercise May Affect The Immune System Against COVID-19? Spor Hekimliği Dergisi, 55(2), 186-187. doi:
Yoon, K. J., Ahn, A., Park, S. H., Kwak, S. H., Kwak, S. E., Lee, W., . . . Kim, H.-R. (2021). Exercise reduces metabolic burden while altering the immune system in aged mice. Aging (Albany NY), 13(1), 1294. doi:
Zhou, P., Yang, X.-L., Wang, X.-G., Hu, B., Zhang, L., Zhang, W., . . . Huang, C.-L. (2020). A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature, 579(7798), 270-273. doi: 695
Zhu, W. (2020). Should, and how can, exercise be done during a coronavirus outbreak? An interview with Dr. Jeffrey A. Woods. Journal of sport and health science, 9(2), 105. doi:
Volume 3, Issue 1
March 2023
Pages 29-42
  • Receive Date: 03 January 2023
  • Revise Date: 17 February 2023
  • Accept Date: 22 February 2023
  • First Publish Date: 22 February 2023