{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T22:42:46Z","timestamp":1788993766425,"version":"build-2803163510"},"reference-count":57,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T00:00:00Z","timestamp":1736899200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JFMK"],"abstract":"<jats:p>Cardiotoxicity, cardiovascular diseases (CVDs), hypertension, hepatotoxicity, and respiratory problems occurring several months to several years post-chemotherapy and\/or radiotherapy are increasingly documented by scientists and clinicians. Anthracyclines, for example, were discovered in the late 1960s to be dose-dependently linked to induced cardiotoxicity, which frequently resulted in cardiomyopathy and heart failure. Most of those changes have also been associated with aging. While it is well known that exercise can slow down cellular aging processes, lessen the effects of chemotherapy, improve the effectiveness of cancer treatments, and prevent health problems in the general population, it remains unclear how exercise volume or intensity may affect the overall benefits of physical activity on health. For instance, higher rates of sudden cardiac arrest or coronary artery calcification have been found in marathon and ultra-marathon runners. Several additional pathological consequences have also been reported recently on many organs of those athletes. This review reports the most recent evidence suggesting that excessive intensity and\/or volume may have deleterious effects on health. These findings are in clear contrast with the popular belief that all forms of physical activity can generally reduce the pathological changes associated with aging or cancer therapies. In conclusion, high-intensity training (HIT) and\/or high-volume training (HVT) should not be recommended for middle-age and elderly people who have had cancer therapies or not in order to avoid an exacerbation of the consequences of aging or long-term cancer treatment effects on vital organ structures and functions.<\/jats:p>","DOI":"10.3390\/jfmk10010033","type":"journal-article","created":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T05:59:42Z","timestamp":1736920782000},"page":"33","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Cardiovascular Diseases, Vital Organ Fibrosis, and Chronic Inflammation Associated with High-Intensity and\/or High-Volume Exercise Training: Double-Edged Sword Effects of Vigorous Physical Activity in Elderly People and\/or in Middle-Age Cancer-Therapy-Treated Patients"],"prefix":"10.3390","volume":"10","author":[{"given":"Pierre A.","family":"Guertin","sequence":"first","affiliation":[{"name":"Department of Neurosciences, Faculty of Medicine, Laval University, Qu\u00e9bec, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"229","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: Globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Nagy, A., B\u00f6rzsei, D., Hoffmann, A., T\u00f6r\u00f6k, S., Veszelka, M., Alm\u00e1si, N., Varga, C., and Szab\u00f3, R. (2024). A comprehensive overview on chemotherapy-induced cardiotoxicity: Insights into the underlying inflammatory and oxidative mechanisms. Cardiovasc. Drugs Ther.","DOI":"10.1007\/s10557-024-07574-0"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"20","DOI":"10.4103\/ijri.IJRI_178_19","article-title":"Chemotherapy-induced pulmonary complications in cancer: Significance of clinicoradiological correlation","volume":"30","author":"Dhamija","year":"2020","journal-title":"Indian J. Radiol. Imaging"},{"key":"ref_4","unstructured":"Phan, S.H., and Thrall, R.S. (1995). Bleomycin. Pulmonary Fibrosis, Dekker."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1378\/chest.07-0851","article-title":"Pulmonary complications of novel antineoplastic agents for solid tumors","volume":"133","author":"Vahid","year":"2008","journal-title":"Chest"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/S1665-2681(19)31651-5","article-title":"Effects of systemic chemotherapy on the liver","volume":"9","author":"Ramadori","year":"2010","journal-title":"Ann. Hepatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1007\/s13244-015-0436-7","article-title":"Cancer therapy related complications in the liver, pancreas, and biliary system: An imaging perspective","volume":"6","author":"Ngo","year":"2015","journal-title":"Insights Imaging"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1002\/bjs.5719","article-title":"Chemotherapy-associated hepatotoxicity and surgery for colorectal liver metastates","volume":"94","author":"Zorzi","year":"2007","journal-title":"Br. J. Surg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1210\/er.2018-00092","article-title":"Long-term endocrine and metabolic consequences of cancer treatment: A systematic review","volume":"40","author":"Gebauer","year":"2019","journal-title":"Endocr. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1038\/s41571-023-00776-9","article-title":"Mitigating long-term and delayed adverse events associated with cancer treatment: Implications for survirship","volume":"20","author":"Lustberg","year":"2023","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_11","first-page":"6095","article-title":"New insights into the activities and toxicities of the old anticancer drug doxorubicin","volume":"288","author":"Qiao","year":"2020","journal-title":"FEBS J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.cger.2015.08.005","article-title":"Long term toxicity of cancer treatment in older patients","volume":"32","author":"Shahrokni","year":"2015","journal-title":"Clin. Geriatr. Med."},{"key":"ref_13","first-page":"29","article-title":"Long-term organ toxicity of oncological therapies","volume":"150","author":"Thong","year":"2025","journal-title":"Dtsch. Med. Wochenschr."},{"key":"ref_14","unstructured":"United Nations (2025, January 12). World Social Report 2023. Available online: https:\/\/www.un.org\/development\/desa\/dspd\/wp-content\/uploads\/sites\/22\/2023\/01\/WSR_2023_Chapter_Key_Messages.pdf."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"102521","DOI":"10.1016\/j.arr.2024.102521","article-title":"Heart rate variability and autonomic nervous system imbalance: Potential biomarkers and detectable hallmarks of aging and inflammaging","volume":"101","author":"Olivieri","year":"2024","journal-title":"Ageing Res. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Opris, C.E., Suciu, H., Opris, C.I., and Gurzu, S. (2024). An Update on Mitral Valve Aging. Life, 14.","DOI":"10.3390\/life14080950"},{"key":"ref_17","first-page":"158","article-title":"Aging and cardiac fibrosis","volume":"2","author":"Bienrnacka","year":"2011","journal-title":"Aging Dis."},{"key":"ref_18","first-page":"23","article-title":"Cardiovascular aging: From cellular and molecular changes to therapeutic interventions","volume":"3","author":"Vakka","year":"2023","journal-title":"J. Cardiovasc. Aging"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Wahid, R.M., Hassan, N.H., Samy, W., Abdelhadi, A.A., Saadawy, S.F., Elsayed, S.F., Seada, S.G., and Mohamed, S.R.A. (2024). Unraveling the hepatic stellate cells mediated mechanisms in aging\u2019s influence on liver fibrosis. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-63644-1"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"213","DOI":"10.4103\/EUS-D-22-00162","article-title":"Pancreatic changes with lifestyle and age: What is normal and what is concerning","volume":"12","author":"Dietrich","year":"2023","journal-title":"Endosc. Ultrasound"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1097\/01.mco.0000134362.76653.b2","article-title":"Muscle tissue changes with aging","volume":"7","author":"Volpi","year":"2004","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"111976","DOI":"10.1016\/j.mad.2024.111976","article-title":"Senescence of skeletal stem cells and their contribution to age-related bone loss","volume":"221","author":"Jeromdesella","year":"2024","journal-title":"Mech. Ageing Dev."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Xu, J., Zhou, L., and Liu, Y. (2020). Cellular senescence in kidney fibrosis: Pathologic significance and therapeutic strategies. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.601325"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mpmed.2020.10.011","article-title":"The physiology of ageing and how these changes affect older people","volume":"49","author":"Preston","year":"2021","journal-title":"Medicine"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1002\/cphy.c110025","article-title":"Lack of exercise is a major cause of chronic diseases","volume":"2","author":"Booth","year":"2012","journal-title":"Compr. Physiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"100404","DOI":"10.1016\/j.apunsm.2023.100404","article-title":"Effects of high-intensity intermittent training on some inflammatory and muscle damage indices in overweight middle-aged men","volume":"58","author":"Rohnejad","year":"2023","journal-title":"Apunt. Sports Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1007\/s40279-021-01561-3","article-title":"Potential long-term health problems associated with ultra-endurance running: A narrative review","volume":"52","author":"Scheer","year":"2022","journal-title":"Sports Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1001\/jama.1996.03540030033028","article-title":"Sudden death in young competitive athletes: Clinical, demographic, and pathological profiles","volume":"276","author":"Maron","year":"1996","journal-title":"JAMA"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Klingert, M., Nikolaidis, P.T., Weiss, K., Thuany, M., Chl\u00edbkov\u00e1, D., and Knechtle, B. (2022). Exercise-associated hyponatremia in marathon runners. J. Clin. Med., 11.","DOI":"10.3390\/jcm11226775"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1056\/NEJMoa1106468","article-title":"Cardiac arrest during long-distance running races","volume":"366","author":"Kim","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_31","first-page":"130","article-title":"Sudden cardiac arrest in a marathon runner. A Case Report","volume":"4","author":"Ghio","year":"2012","journal-title":"HSR Proc. Intensive Care Cardiovasc. Anesth."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.1249\/MSS.0b013e318258b59a","article-title":"Suddent cardiac arrest and death in United States marathons","volume":"44","author":"Webner","year":"2012","journal-title":"Med. Sci. Sports Exerc."},{"key":"ref_33","first-page":"1399","article-title":"A comparison of the physiological demands imposed by competing in a half-marathon vs. a marathon","volume":"57","author":"Salinera","year":"2017","journal-title":"J. Sports Med. Phys. Fit."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1016\/S0002-9149(01)01909-9","article-title":"Effects of marathon running on inflammatory and hemostatic markers","volume":"88","author":"Siegel","year":"2001","journal-title":"Am. J. Cardiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/j.mayocp.2012.04.005","article-title":"Potential adverse cardiovascular effects from excessive endurance exercise","volume":"87","author":"Patil","year":"2012","journal-title":"Mayo Clin. Proc."},{"key":"ref_36","unstructured":"Coylewright, M. (2017). Extreme Long-Distance Running Has Questionable Impact on Heart, American College of Cardiology."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.mayocpiqo.2019.03.009","article-title":"Assessment of coronary atherosclerosis using calcium scores in short- and long-distance runners","volume":"3","author":"Jafar","year":"2019","journal-title":"Mayo Clin. Proc. Innov. Qual. Outcomes"},{"key":"ref_38","first-page":"443","article-title":"Diseases and overuse injuries of the lower extremities in long distance runners","volume":"76","author":"Tshopp","year":"2017","journal-title":"Z. Rheumatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1007\/s40279-020-01417-2","article-title":"Do sex differences in physiology confer a female advantage in ultra-endurance sport?","volume":"51","author":"Tiller","year":"2021","journal-title":"Sports Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1123\/ijsnem.2018-0288","article-title":"Exercise-induced illness and inflammation: Can immunonutrition and iron help","volume":"29","author":"Castell","year":"2019","journal-title":"Int. Sport Nutr. Exerc. Metab."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1046\/j.1365-2141.2003.04151_6.x","article-title":"Intensive triathtlon training induces low peripheral CD34+ stem cells","volume":"120","author":"Philip","year":"2003","journal-title":"Br. J. Haematol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1136\/bjsm.2006.030569","article-title":"High incidence of exercise-induced bronchoconstriction in triathletes of the Swiss National Team","volume":"41","author":"Burki","year":"2007","journal-title":"Br. J. Sports Med."},{"key":"ref_43","first-page":"e7814","article-title":"Severe kidney injury after a 110-km trail race","volume":"12","author":"Scheer","year":"2020","journal-title":"Cureus"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1814","DOI":"10.1080\/02640414.2015.1012104","article-title":"GI distress is common during a 161-km ultramarathon","volume":"33","author":"Stuempfle","year":"2015","journal-title":"J. Sports Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1900\/RDS.2019.15.35","article-title":"Impact of physical exercise on gut microbiome, inflammation, and the pathobiology of metabolic disorders","volume":"15","author":"Sohail","year":"2019","journal-title":"Rev. Diabet. Stud."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.cyto.2012.11.019","article-title":"Leukocyte chemotactic cytokine and leukocyte subset responses during ultra-marathon running","volume":"61","author":"Shin","year":"2013","journal-title":"Cytokine"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.wem.2014.03.013","article-title":"The impact of an ultramarathon on hormonal and biochemical parameters in men","volume":"25","author":"Kupchak","year":"2014","journal-title":"Wilderness Environ. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e85","DOI":"10.1016\/j.jsams.2010.10.642","article-title":"The open window of susceptibility to infection after acute exercise in healthy young male elite athletes","volume":"13","author":"Kakanis","year":"2010","journal-title":"J. Sci. Med. Sport"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Freund, W., Faust, S., Birklein, F., Gaser, C., Wunderlich, A.P., M\u00fcller, M., Billich, C., Juchems, M.S., Schmitz, B.L., and Gr\u00f6n, G. (2012). Substantial and reversible brain gray matter reduction but no acute brain lesions in ultramarathon runners. BMC Med., 10.","DOI":"10.1186\/1741-7015-10-170"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1080\/15438627.2018.1431533","article-title":"Ultra-obligatory running among ultramarathon runners","volume":"26","author":"Hoffman","year":"2018","journal-title":"Res. Sports Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1007\/s11920-023-01447-3","article-title":"Cognitive problems in perimenopause: A review of recent evidence","volume":"25","author":"Metcalf","year":"2023","journal-title":"Curr. Psychiatry Rep."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Thuany, M., Gomes, T.N., Villiger, E., Weiss, K., Scheer, V., Nikolaidis, P.T., and Knechtle, B. (2022). Trends in participation, sex differences and age of peak performance in time-limited ultramarathon events: A secular analysis. Medicina, 58.","DOI":"10.3390\/medicina58030366"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"105843","DOI":"10.1016\/j.psyneuen.2022.105843","article-title":"The effects of physical activity on cortisol and sleep: A systemic review and meta-analysis","volume":"143","author":"Anderson","year":"2022","journal-title":"Psychoneuroendocrinology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1249\/MSS.0000000000001936","article-title":"Physical activity, cognition, and brain outcomes: A review of the 2018 physical activity guidelines","volume":"51","author":"Erickson","year":"2019","journal-title":"Med. Sci. Sports Exerc."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"De la Corte-Rodriguez, H., Roman-Belmonte, J.M., Resino-Luis, C., Madrid-Gonzalez, J., and Rodriguez-Merchan, E.C. (2024). The role of physical exercise in chronic musculoskeletal pain: Best medicine- a narrative review. Healthcare, 12.","DOI":"10.3390\/healthcare12020242"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.jshs.2024.02.002","article-title":"The anti-inflammatory effects of exercise on autoimmune diseases: A 20-year systematic review","volume":"13","author":"Luo","year":"2024","journal-title":"J. Sport Health Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/bs.adgen.2024.01.002","article-title":"Microbiome and physical activity","volume":"111","author":"Odriozola","year":"2024","journal-title":"Adv. Genet."}],"container-title":["Journal of Functional Morphology and Kinesiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2411-5142\/10\/1\/33\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:29:10Z","timestamp":1759919350000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2411-5142\/10\/1\/33"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,15]]},"references-count":57,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["jfmk10010033"],"URL":"https:\/\/doi.org\/10.3390\/jfmk10010033","relation":{},"ISSN":["2411-5142"],"issn-type":[{"value":"2411-5142","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,15]]}}}