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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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“controls secretion of IL-1β and IL-18 in leukocytes [73].”
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“In a mouse model of Parkinson’s disease, AMPK activation reversed behavioral impairments, reduced α-synuclein accumulation and enhanced LC3II-mediated autophagy in dopaminergic neurons [138, 139].”
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“Additionally, activation of peroxisome proliferator-activated receptor gamma (PGC-1α) improves muscle endurance, mitochondrial remodeling and enhanced balance and motor coordination in animal models [46].”
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“regulated after exercise training in older women [74] and could underlie the promotion of health span and longevity.”
BackgroundGrowth Factors as Mediators of Exercise Actions on the Brain
Llorens-Martı́n, M., Torres‐Alemán, I., & Trejo, J. L. (2008) · NeuroMolecular Medicine · doi:10.1007/s12017-008-8026-1 · Cited by 65
Vasilaki, A., van der Meulen, J. H., Larkin, L. M., Harrison, D. C., Pearson, T., Remmen, H. V., Richardson, A., Brooks, S. V., Jackson, M. J., & McArdle, A. (2010) · Aging Cell · doi:10.1111/j.1474-9726.2010.00635.x · Cited by 60 · cited 1×
“A study using mice lacking the Cu, Zn superoxide dismutase showed an accelerated, agerelated loss of muscle mass and function which correlated to chronic exposure to increased oxidant activity [44].”
BackgroundHypertension and Exercise Training: Evidence from Clinical Studies
Moraes-Silva, I. C., Mostarda, C. T., Silva‐Filho, A. C., & Irigoyen, M. C. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-981-10-4304-8_5 · Cited by 57 · cited 1×
“After a myocardial infarction, exercise has been shown to prevent future complications, improve the quality of life and longevity of patients [33].”
BackgroundXu, B. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.10.008 · Cited by 52
The role of exercise capacity in the health and longevity of centenarians
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“In this unique population, the decline in lung function and sarcopenia can be counteracted by exercise programs which increase their physical capacity and health span [24].”
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“High levels of exercise have been associated with better executive function and memory in cross-sectional and longitudinal analyses [49].”
BackgroundEffect of chronic contractile activity on mRNA stability in skeletal muscle
Lai, R. Y. J., Ljubicic, V., D’Souza, D. M., & Hood, D. A. (2010) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00523.2009 · Cited by 47 · cited 1×
“Exercise downregulates this inflammatory response through AUF1 [110], a decay factor implicated in maintenance of telomere length by TERT modulation [111].”
BackgroundHepatoprotective Effects of Swimming Exercise against D-Galactose-Induced Senescence Rat Model
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“AMPK-activation has also been shown to rescue misfolding and trafficking of rhodopsin, highlighting the AMPK role against impairment in proteostasis [140] (Figure 2).”
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“Current research is exploring intermittent fasting as an alternative with beneficial antiaging effects at a cellular level in animals and humans [26, 27].”
BackgroundMetformin delays satellite cell activation and maintains quiescence
Pavlidou, T., Marinkovic, M., Rosina, M., Fuoco, C., Vumbaca, S., Gargioli, C., Castagnoli, L., & Cesareni, G. (2019) · Stem Cells International · doi:10.1155/2019/5980465 · Cited by 38 · cited 1×
“In addition, activation of Gpx7 via Nrf2 delayed cellular attrition related to stem cell aging [128, 129]”
BackgroundProphylactic effects of swimming exercise on autophagy-induced muscle atrophy in diabetic rats
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“Additionally, the protective effect of chronic exercise on diabetesinduced muscle atrophy is partly due to decreased muscle autophagy [77].”
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“In addition, exercise activates pluripotent cell progenitors in several tissues, including mesenchymal and neural stem cells leading to improved brain regenerative capacity and cognitive ability [107].”
BackgroundWhich type of exercise keeps you young?
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“com 3 AGING should be added to minimize loss of muscle mass that is characteristic of aging and disease [23].”
BackgroundLate‐life time‐restricted feeding and exercise differentially alter healthspan in obesity
Schafer, M. J., Mazula, D. L., Brown, A. K., White, T. A., Atkinson, E. J., Pearsall, V. M., Aversa, Z., Verzosa, G., Smith, L. A., Matveyenko, A. V., et al. (2019) · Aging Cell · doi:10.1111/acel.12966 · Cited by 23 · cited 1×
“maladaptation) [25] and should therefore be a first line choice as an antiaging strategy.”
Background
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Exercise sustains the hallmarks of health
Qiu, Y., Fernández-García, B., Lehmann, H. I., Li, G., Kroemer, G., López-Otín, C., & Xiao, J. (2023) · Journal of Sport and Health Science · doi:10.1016/j.jshs.2022.10.003 · Cited by 270
Izquierdo, M., de Souto Barreto, P., Arai, H., Bischoff-Ferrari, H. A., Cadore, E. L., Cesari, M., Chen, L.-K., Coen, P. M., Courneya, K. S., Duque, G., et al. (2025) · The Journal of nutrition, health and aging · doi:10.1016/j.jnha.2024.100401 · Cited by 273
Neurogenesis in aging and age-related neurodegenerative diseases
Čulig, L., Chu, X., & Bohr, V. A. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101636 · Cited by 235
Aging of mesenchymal stem cell: machinery, markers, and strategies of fighting
Al‐Azab, M., Safi, M., Idiiatullina, E., Al‐Shaebi, F., & Zaky, M. Y. (2022) · Cellular & Molecular Biology Letters · doi:10.1186/s11658-022-00366-0 · Cited by 178
The Role of Immune Cells in Oxi-Inflamm-Aging
de Toda, I. M., Ceprián, N., Cerro, E. D., & la Fuente, M. D. (2021) · Cells · doi:10.3390/cells10112974 · Cited by 124
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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