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Effects of exercise on cellular and tissue aging
Open accessAbstract
The natural aging process is carried out by a progressive loss of homeostasis leading to a functional decline in cells and tissues. The accumulation of these changes stem from a multifactorial process on which both external (environmental and social) and internal (genetic and biological) risk factors contribute to the development of adult chronic diseases, including type 2 diabetes mellitus (T2D). Strategies that can slow cellular aging include changes in diet, lifestyle and drugs that modulate intracellular signaling. Exercise is a promising lifestyle intervention that has shown antiaging effects by extending lifespan and healthspan through decreasing the nine hallmarks of aging and age-associated inflammation. Herein, we review the effects of exercise to attenuate aging from a clinical to a cellular level, listing its effects upon various tissues and systems as well as its capacity to reverse many of the hallmarks of aging. Additionally, we suggest AMPK as a central regulator of the cellular effects of exercise due to its integrative effects in different tissues. These concepts are especially relevant in the setting of T2D, where cellular aging is accelerated and exercise can counteract these effects through the reviewed antiaging mechanisms.
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“Exercise training has been shown to reduce all the hallmarks of ageing9,3,38”
From Exercise activates AMPK in mouse and human pancreatic islets to decrease senescence (2024) · cites this paper as [9]
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“1 possible to reverse aging, but strategies based on the adoption of a healthy lifestyle associated with regular physical exercise and a balanced diet can delay its deleterious effects with positive repercussions on the physical fitness of populations, that is, on the ability to perform activities of daily living with…”
BackgroundStarting Physical Activity From Scratch is Never Easy
Criss, M. G., Irwin, K. E., & Wingood, M. (2024) · Topics in Geriatric Rehabilitation · doi:10.1097/tgr.0000000000000451 · Cited by 1
Nicotinamide Adenine Dinucleotide and Aging
Jiang, Z., Luo, L., Qin, Y., Huang, Y., & Yan, S. (2025) · Springer eBooks · doi:10.1007/978-981-97-9877-3_28 · Cited by 1
Minuzzi, L. G., Teixeira, A. A. D. S., Figueiredo, C., Dorneles, G. P., Branco, A. C. C. C., Silva, B. S. D. A., Valenzuela, P. L., Peres, A., Lucı́a, A., Sato, M. N., et al. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1601405 · Cited by 1
“Aging is known to impact immune function, including alterations in cell-type-speci fi c signaling pathways and expression of receptors (14, 28, 29), thereby impairing endotoxin tolerance (15).”
Goki, M. M., Rostamzadeh, F., Jafarinejad‐Farsangi, S., Jafari, E., Soltani, Z., Mansouri, S., & Askarimoghadam, H. (2025) · European Journal of Applied Physiology · doi:10.1007/s00421-025-06005-8 · Cited by 1
Mechanisms of aging in the cardiovascular system: challenges and opportunities
Zhao, X., Yang, X., Lin, Y., Lei, R., Ding, W., He, X.-Y., Cao, Y. J., Zhang, D., Liu, P., Liang, M., et al. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1635736 · Cited by 4
“In addition, regular aerobic exercise can reduce oxidative stress in ECs and suppress aging-related in fl ammatory processes (256).”
Environmental Influences on Genetic Aging Processes: Experimental Evidence from Model Systems
Molla, A. (2025) · European Journal of Clinical and Biomedical Sciences · doi:10.11648/j.ejcbs.20251104.12 · Cited by 1
Subham, Jindal, R., Sharma, S. S., Uppal, H., George, S., & Sharma, R. (2025) · Indian Journal of Physiology and Pharmacology · doi:10.25259/ijpp_406_2025 · Cited by 1
Li, H., Chen, Z., & Songlin, X. (2026) · Cell Biochemistry and Biophysics · doi:10.1007/s12013-026-02004-4 · Cited by 1
“At a cellular level, exercise can minimize DNA lesions, enhance DNA repair mechanisms, and increase the muscle’s resistance to oxidative stress [143].”
Sex specific effects of irisin on the skeleton
Shimonty, A., & Bonewald, L. F. (2026) · Bone Research · doi:10.1038/s41413-026-00542-4 · Cited by 1
“139,140 Irisin level decreases with age, which can be partially recovered with exercise.”
Zábó, V., Ceglédi, A., Buda, A., Varga, P., Fekete, M., Fazekas‐Pongor, V., Csípő, T., Adonicsné-Püski, K., Giovannetti, G., Loscalzo, Y., et al. (2026) · GeroScience · doi:10.1007/s11357-026-02339-z · Cited by 1
Educação em saúde, envelhecimento e bem-estar
de Miranda, M. G., de Farias, H. P. S., & de Farias, B. M. (2022) · EPITAYA eBooks · doi:10.47879/ed.ep.2022625 · Cited by 1
Barreto, P. D. S. (2023) · Journal of Aging Research and Lifestyle · doi:10.14283/jarlife.2023.5 · Cited by 2
Mindful Approaches to Sustainable Healthcare: Nurturing Mental Health and Well-Being
Saxena, R., Saxena, S., & Singh, A. P. (2024) · World sustainability series · doi:10.1007/978-3-031-60545-1_14 · Cited by 1
The possible biomarkers of the «postСovid-19 syndrome» in patients with type 2 diabetes
Jburi, L. R., & Kopylova, M. V. (2022) · ТЕНДЕНЦИИ РАЗВИТИЯ НАУКИ И ОБРАЗОВАНИЯ · doi:10.18411/trnio-04-2022-88
Gao, Y. (2022) · Springer eBooks · doi:10.1007/978-981-19-7122-8_21
Magalhães, C. O. D. E., Mendes, B. F., Dias, I. R., Pereira, R. R. D. S., Pereira, G. C., Lee, K. S., de Souza, R. A. L., Dias‐Peixoto, M. F., & Cassilhas, R. C. (2023) · SSRN Electronic Journal · doi:10.2139/ssrn.4661068
Advances in the Study of NLRP3 in the Inflammatory Response to Exercise and Metabolic Syndrome
Yu-xiang, H., Wang, H., Xiao-Min, D., & Chong-lin, Z. (2024) · Medical Research Frontiers · doi:10.57237/j.mrf.2024.01.002
Kalkan, K. K., Şirin, N., Tepe, A., Gök, A., Altaş, T., Ağan, K., Gülhan, P. Y., & Alpay, M. (2024) · Clinical and Experimental Health Sciences · doi:10.33808/clinexphealthsci.1369239
Yoga may attenuates hallmarks of skin aging
Kumari, A., & Medharthi, N. (2024) · IP Indian Journal of Clinical and Experimental Dermatology · doi:10.18231/j.ijced.2024.044 · Cited by 2
Xu, Q., & Gao, Y. (2025) · Geriatrics and gerontology international/Geriatrics & gerontology international · doi:10.1111/ggi.70085
“4 Characterizing which PA modalities (e.g. high-intensity interval vs moderate continuous training) most effectively modulate these pathways could inform personalized exercise prescriptions.”
Elmi, F., Soltanmohammadi, F., Keshavarz, P., & Alizadeh, E. (2025) · Food Bioscience · doi:10.1016/j.fbio.2025.107311 · Cited by 1
Aya, V., Jiménez, P., Muñoz, E., & Ramírez, J. D. (2024) · Figshare · doi:10.6084/m9.figshare.26596778
Aya, V., Jiménez, P., Muñoz, E., & Ramírez, J. D. (2024) · Figshare · doi:10.6084/m9.figshare.26596781
Dermatological Disorders in Older Adults: Geriatrician’s Perspective
Dharmarajan, T. S. (2025) · Springer eBooks · doi:10.1007/978-3-031-53888-9_2-1
Schab, A. R., McCarroll, T. R., Walsh, E., Kahana-Rojkind, A. H., Quesada-Jimenez, R., & Domb, B. G. (2026) · The American Journal of Sports Medicine · doi:10.1177/03635465251407118
“10,17,27,29,30,40 In agreement with this notion, a prospective study with 71,893 senior adults showed that 15 to 20 minutes of vigorous physical activity each week lowers all-cause mortality by 18% to 24%.”
Exercise and aging: Unlocking health beyond 65 years old
Puche, J. E. (2026) · Aging advances. · doi:10.4103/agingadv.agingadv-d-25-00036
Castillo, R. L., Jofré‐Saldía, E., Cáceres-Vergara, D., Renard, G. M., & Figueroa, E. G. (2026) · Biomedicines · doi:10.3390/biomedicines14040875
“For example, long-term physical training has been shown to reduce oxidative stress and inflammation while enhancing DNA repair mechanisms and proteostasis in mixed-sex cohorts [58,59].”
Mitochondrial Signaling and Stress Responses, Key Regulators of Aging and Longevity
SHENG, Y., Markovich, Z., Han, S. M., & Xiao, R. (2026) · BioEssays · doi:10.1002/bies.70146
“However, this process remains plastic: interventions such as caloric restriction, endurance exercise, and pharmacologic activation of AMPK (e.g., via metformin or AICAR) can restore biogenesis and improve tissue function in aged animals [145–148].”
Gordon, B. D. H., Howden, R., McWhorter, M. L., Gaillard, E. C., Alessi, M. G., Persin, M. J., Kachmarik, J. E., Price, B. C., Snapper, L. A., Sombatsaphay, V., et al. (2026) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2026.106870
Proteomic ageing clocks: methods, mechanisms and the muscle connection
Reisman, E. G., Jacques, M., Grolaux, R., Gladyshev, V. N., & Eynon, N. (2026) · Genome biology · doi:10.1186/s13059-026-04220-w
“Protein abundance is modifiable through interventions such as exercise, nutrition, and pharmacological treatment, positioning proteomic clocks as potentially more responsive indicators of biological ageing dynamics [15–17].”
Toward a context-aware geroscience: integrating structural and social context into aging biology
Bellizzi, K. M., Kuchel, G. A., Redeker, N. S., & Nwakasi, C. C. (2026) · The Gerontologist · doi:10.1093/geront/gnag179
Metadata
- Authors
- Carapeto, P. V., & Aguayo-Mazzucato, C.
- Affiliations
- Joslin Diabetes Center (US)
- Beta Cell Aging Lab, Joslin Diabetes Center, Harvard Medical School, Boston MA 02115, USA
- Venue
- Aging
- Publisher
- Impact Journals, LLC
- Published
- 2021-05-13
- Volume
- 13
- Issue
- 10
- Pages
- 14522-14543
- ISSN
- 1945-4589 (ISSN-L)
- PMC
- PMC8202894
- OpenAlex
- W3162660575
- Cited by
- 107
- References
- 166
- Citations by year
- 2026: 21 · 2025: 23 · 2024: 31 · 2023: 14 · 2022: 13 · 2021: 5
- FWCI
- 1.29
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by
- Locations
- Aging (publishedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK036836)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Physiology (medical) › Exercise and Physiological Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- physical activity, cellular aging, tissue aging, hallmarks of aging, type 2 diabetes, AMPK, healthspan, lifespan extension, age-associated inflammation, lifestyle intervention
- MeSH terms
- Adenylate Kinase, Aging, Animals, Humans, Organ Specificity, Signal Transduction, Exercise, Cellular Senescence, Models, Animal
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