Physical Exercise Prevents Cellular Senescence in Circulating Leukocytes and in the Vessel Wall
Abstract
Background— The underlying molecular mechanisms of the vasculoprotective effects of physical exercise are incompletely understood. Telomere erosion is a central component of aging, and telomere-associated proteins regulate cellular senescence and survival. This study examines the effects of exercising on vascular telomere biology and endothelial apoptosis in mice and the effects of long-term endurance training on telomere biology in humans. Methods and Results— C57/Bl6 mice were randomized to voluntary running or no running wheel conditions for 3 weeks. Exercise upregulated telomerase activity in the thoracic aorta and in circulating mononuclear cells compared with sedentary controls, increased vascular expression of telomere repeat-binding factor 2 and Ku70, and reduced the expression of vascular apoptosis regulators such as cell-cycle–checkpoint kinase 2, p16, and p53. Mice preconditioned by voluntary running exhibited a marked reduction in lipopolysaccharide-induced aortic endothelial apoptosis. Transgenic mouse studies showed that endothelial nitric oxide synthase and telomerase reverse transcriptase synergize to confer endothelial stress resistance after physical activity. To test the significance of these data in humans, telomere biology in circulating leukocytes of young and middle-aged track and field athletes was analyzed. Peripheral blood leukocytes isolated from endurance athletes showed increased telomerase activity, expression of telomere-stabilizing proteins, and downregulation of cell-cycle inhibitors compared with untrained individuals. Long-term endurance training was associated with reduced leukocyte telomere erosion compared with untrained controls. Conclusions— Physical activity regulates telomere-stabilizing proteins in mice and in humans and thereby protects from stress-induced vascular apoptosis.
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Exercise can effectively reduce the appearance of age-related markers, such as p16, so as to achieve the effect of delaying aging.
“These evidence suggest that exercise can effectively reduce the appearance of age-related markers, such as p16, so as to achieve the effect of delaying aging.”
From Inflammation and aging: signaling pathways and intervention therapies (2023) · cites this paper as [333]
Middle-aged marathon/triathletes had higher telomerase activity and longer telomere length in circulating white blood cells compared to the control group.
“Recent study found that middle-aged marathon/triathletes had higher telomerase activity and longer telomere length in circulating white blood cells compared to the control group.333”
From Inflammation and aging: signaling pathways and intervention therapies (2023) · cites this paper as [333]
Telomerase activity and TRF2 protein abundance were significantly higher in young and middle-aged professional long-distance runners compared with their untrained peers.
“In this same study, both telomerase activity and TRF2 protein abundance were also significantly higher in young (early 20s) and middle-aged (early 50s) professional long-distance runners compared with their untrained peers.”
From Exercise Counters the Age-Related Accumulation of Senescent Cells (2022) · cites this paper as [17]
Exercised mice had increased expression of TRF1, TRF2, and Ku70 in the aorta, which has been shown to protect against telomere erosion and genome degradation.
“In younger mice, neither 3 wk nor 6 months of voluntary wheel running affected telomere length within the aorta, although exercised mice had increased expression of telomere repeat-binding factor 1 (TRF1), TRF2, and Ku70 in the aorta, which has been shown to protect against telomere erosion and genome degradation (17).”
From Exercise Counters the Age-Related Accumulation of Senescent Cells (2022) · cites this paper as [17]
In younger mice, neither 3 wk nor 6 months of voluntary wheel running affected telomere length within the aorta.
“In younger mice, neither 3 wk nor 6 months of voluntary wheel running affected telomere length within the aorta, although exercised mice had increased expression of telomere repeat-binding factor 1 (TRF1), TRF2, and Ku70 in the aorta, which has been shown to protect against telomere erosion and genome degradation (17).”
From Exercise Counters the Age-Related Accumulation of Senescent Cells (2022) · cites this paper as [17]
Telomerase activity was higher in the aorta and mononuclear cells isolated from the blood, spleen, and bone marrow of mice exercised for 3 wk compared with sedentary controls.
“In addition, telomerase activity was higher in the aorta and mononuclear cells isolated from the blood, spleen, and bone marrow of mice exercised for 3 wk compared with sedentary controls.”
From Exercise Counters the Age-Related Accumulation of Senescent Cells (2022) · cites this paper as [17]
Similar effects were observed in the myocardium and aorta with longer-term (6 months) voluntary wheel running.
“Similar effects were observed in the myocardium and aorta with longer-term (6 months) voluntary wheel running (17).”
From Exercise Counters the Age-Related Accumulation of Senescent Cells (2022) · cites this paper as [17]
Healthy middle-aged marathon runners/triathletes have lower P53 and P16 in circulating leukocytes compared with untrained controls.
“Healthy middle-aged marathon runners/triathletes have lower P53 and P16 in circulating leukocytes, greater telomerase activity and telomere length, and higher expression of telomere-stabilizing proteins compared with untrained controls (17).”
From Exercise Counters the Age-Related Accumulation of Senescent Cells (2022) · cites this paper as [17]
Healthy middle-aged marathon runners/triathletes have greater telomerase activity and telomere length compared with untrained controls.
“Healthy middle-aged marathon runners/triathletes have lower P53 and P16 in circulating leukocytes, greater telomerase activity and telomere length, and higher expression of telomere-stabilizing proteins compared with untrained controls (17).”
From Exercise Counters the Age-Related Accumulation of Senescent Cells (2022) · cites this paper as [17]
Healthy middle-aged marathon runners/triathletes have higher expression of telomere-stabilizing proteins compared with untrained controls.
“Healthy middle-aged marathon runners/triathletes have lower P53 and P16 in circulating leukocytes, greater telomerase activity and telomere length, and higher expression of telomere-stabilizing proteins compared with untrained controls (17).”
From Exercise Counters the Age-Related Accumulation of Senescent Cells (2022) · cites this paper as [17]
Physical activity bolsters mediating immune proteins and gene expression and more distal biological aging endpoints, such as mitochondrial health and telomerase levels, which are related to telomere maintenance.
“Physical activity also bolsters mediating immune proteins and gene expression (74,75) and more distal biological aging endpoints, such as mitochondrial health and telomerase levels (76–79), which are intimately related to telomere maintenance (20,80,81).”
From Determinants of telomere attrition over 1 year in healthy older women: stress and health behaviors matter (2015) · cites this paper as [76]
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References 34 · Cited by 380
- Authors
- Werner, C., Fürster, T., Widmann, T., Pöss, J., Roggia, C., Hanhoun, M., Scharhag, J., Büchner, N., Meyer, T., Kindermann, W., Haendeler, J., Böhm, M., & Laufs, U.
- Affiliations
- Universitätsklinikum des Saarlandes (DE)
- From the Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin (C.W., T.F., J.P., M.H., M.B., U.L.), Klinik für Innere Medizin I, Onkologie, Hämatologie, Klinische Immunologie und Rheumatologie (T.W.), and Institut für Pathologie (C.R.), Universitätsklinikum des Saarlandes, Homburg/Saar, Germany; Institut für Sport und Präventivmedizin, Universität des Saarlandes, Saarbrücken (J.S., T.M., W.K.); and Institut für Umweltmedizinische Forschung at the...
- Venue
- Circulation
- Published
- 2009-12-15
- Volume
- 120
- Issue
- 24
- Pages
- 2438-2447
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2148768345
- Cited by
- 380
- References
- 34
- Citations by year
- 2026: 10 · 2025: 15 · 2024: 28 · 2023: 23 · 2022: 28 · 2021: 25 · 2020: 31 · 2019: 16 · 2018: 27 · 2017: 22 · 2016: 28 · 2015: 22 · 2014: 23 · 2013: 21 · 2012: 21
- FWCI
- 13.52
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- physical activity, cellular senescence, telomere biology, telomerase activity, endothelial cell apoptosis, vascular aging, endurance training, leukocytes, Ku70, p16, p53, endothelial nitric oxide synthase, telomerase reverse transcriptase, aorta, track and field athletes
- MeSH terms
- Adolescent, Adult, Animals, Blood Vessels, Endothelium, Vascular, Physical Exertion, Female, Humans, Leukocytes, Male, Mice, Inbred C57BL, Mice, Transgenic, Middle Aged, Physical Conditioning, Animal, Running, Exercise, Telomere, Cellular Senescence, Mice, Young Adult
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