The DOI matches its Crossref record; 55 of the 55 references it cites were found in a registry or an index.
Effects of Physical Exercise on Myocardial Telomere-Regulating Proteins, Survival Pathways, and Apoptosis
Open accessAbstract
Objectives The purpose of this study was to study the underlying molecular mechanisms of the protective cardiac effects of physical exercise.Background Telomere-regulating proteins affect cellular senescence, survival, and regeneration.Methods C57/Bl6 wild-type, endothelial nitric oxide synthase (eNOS)-deficient and telomerase reverse transcriptase (TERT)-deficient mice were randomized to voluntary running or no running wheel conditions (n = 8 to 12 per group).Results Short-term running (21 days) up-regulated cardiac telomerase activity to >2-fold of sedentary controls, increased protein expression of TERT and telomere repeat binding factor (TRF) 2, and reduced expression of the proapoptotic mediators cell-cycle-checkpoint kinase 2 (Chk2), p53, and p16. Myocardial and leukocyte telomere length did not differ between 3-week- and 6-month-old sedentary or running mice, but telomerase activity, TRF2 and TERT expression were persistently increased after 6 months and the expression of Chk2, p53, and p16 remained down-regulated. The exercise-induced changes were absent in both TERT(-/-) and eNOS(-/-) mice. Running increased cardiac expression of insulin-like growth factor (IGF)-1. Treatment with IGF-1 up-regulated myocardial telomerase activity >14-fold and increased the expression of phosphorylated Akt protein kinase and phosphorylated eNOS. To test the physiologic relevance of these exercise-mediated prosurvival pathways, apoptotic cardiomyopathy was induced by treatment with doxorubicin. Up-regulation of telomere-stabilizing proteins by physical exercise in mice reduced doxorubicin-induced p53 expression and potently prevented cardiomyocyte apoptosis in wild-type, but not in TERT(-/-) mice.Conclusions Long- and short-term voluntary physical exercise up-regulates cardiac telomere-stabilizing proteins and thereby induces antisenescent and protective effects, for example, to prevent doxorubicin-induced cardiomyopathy. These beneficial cardiac effects are mediated by TERT, eNOS, and IGF-1.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Short-term (3 wk) voluntary wheel running started at 8 wk of age significantly increased myocardial telomerase activity and the protein expression of two telomere-stabilizing proteins, telomerase reverse transcriptase (TERT) and TRF2 in male mice compared with sedentary controls.”
From Exercise Counters the Age-Related Accumulation of Senescent Cells (2022) · cites this paper as [50]
In the citing paper
“When endothelial nitric oxide synthase (eNOS) knockout mice or TERT knockout mice (8-wk-old) were subjected to the same training stimulus, the positive effects of exercise were not present, suggesting that these enzymes are crucial mediators of myocardial and aortic adaptation.”
From Exercise Counters the Age-Related Accumulation of Senescent Cells (2022) · cites this paper as [50]
In the citing paper
“Increased telomerase activity was associated with reduced myocardial levels of P16, P53, and cell-cycle-checkpoint kinase 2 (Chk2) (50).”
From Exercise Counters the Age-Related Accumulation of Senescent Cells (2022) · cites this paper as [50]
In the citing paper
“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 [77]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Danial, N. N., & Korsmeyer, S. J. (2004) · Cell · doi:10.1016/s0092-8674(04)00046-7 · Cited by 4,651
Outcome of Heart Failure with Preserved Ejection Fraction in a Population-Based Study
Bhatia, R. S., Tu, J. V., Lee, D. S., Austin, P. C., Fang, J., Haouzi, A., Gong, Y., & Liu, P. P. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa051530 · Cited by 1,959
Association between telomere length in blood and mortality in people aged 60 years or older
Cawthon, R. M., Smith, K. R., O'Brien, E., Sivatchenko, A., & Kerber, R. A. (2003) · The Lancet · doi:10.1016/s0140-6736(03)12384-7 · Cited by 1,761
TRF2 Protects Human Telomeres from End-to-End Fusions
van Steensel, B., Smogorzewska, A., & de Lange, T. (1998) · Cell · doi:10.1016/s0092-8674(00)80932-0 · Cited by 1,709
Telomeres and human disease: ageing, cancer and beyond
Blasco, M. A. (2005) · Nature Reviews Genetics · doi:10.1038/nrg1656 · Cited by 1,434
Walking Compared with Vigorous Exercise for the Prevention of Cardiovascular Events in Women
Manson, J. E., Greenland, P., LaCroix, A. Z., Stefanick, M. L., Mouton, C. P., Oberman, A., Perri, M. G., Sheps, D. S., Pettinger, M. B., & Siscovick, D. S. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa021067 · Cited by 1,349
Effect of Exercise on Coronary Endothelial Function in Patients with Coronary Artery Disease
Hambrecht, R., Wolf, A., Gielen, S., Linke, A., Hofer, J., Erbs, S., Schoene, N., & Schuler, G. (2000) · New England Journal of Medicine · doi:10.1056/nejm200002173420702 · Cited by 1,340
Chin, L., Artandi, S. E., Shen, Q., Tam, A., Lee, S.-L., Gottlieb, G. J., Greider, C. W., & DePinho, R. A. (1999) · Cell · doi:10.1016/s0092-8674(00)80762-x · Cited by 979
Hambrecht, R., Fiehn, E., Weigl, C., Gielen, S., Hamann, C., Kaiser, R., Yu, J., Adams, V., Niebauer, J., & Schuler, G. C. (1998) · Circulation · doi:10.1161/01.cir.98.24.2709 · Cited by 963
p53-induced inhibition of Hif-1 causes cardiac dysfunction during pressure overload
Sano, M., Minamino, T., Toko, H., Miyauchi, H., Orimo, M., Qin, Y., Akazawa, H., Tateno, K., Kayama, Y., Harada, M., et al. (2007) · Nature · doi:10.1038/nature05602 · Cited by 911
Heterogeneity in telomere length of human chromosomes
Lansdorp, P. M. (1996) · Human Molecular Genetics · doi:10.1093/hmg/5.5.685 · Cited by 886
Laufs, U., Werner, N., Link, A., Endres, M., Waßmann, S., Jürgens, K., Miche, E., Böhm, M., & Nickenig, G. (2003) · Circulation · doi:10.1161/01.cir.0000109141.48980.37 · Cited by 858
Self-citationBrouilette, S., Moore, J. S., McMahon, A. D., Thompson, J. R., Ford, I., Shepherd, J., Packard, C. J., & Samani, N. J. (2007) · The Lancet · doi:10.1016/s0140-6736(07)60071-3 · Cited by 747
Sherr, C. J., & DePinho, R. A. (2000) · Cell · doi:10.1016/s0092-8674(00)00046-5 · Cited by 745
Kim, N. (1997) · Nucleic Acids Research · doi:10.1093/nar/25.13.2595 · Cited by 688
Physical Training Improves Endothelial Function in Patients With Chronic Heart Failure
Hornig, B., Maier, V., & Drexler, H. (1996) · Circulation · doi:10.1161/01.cir.93.2.210 · Cited by 628
Effects of Walking on Mortality among Nonsmoking Retired Men
Hakim, A. A., Petrovitch, H., Burchfiel, C. M., Ross, G. W., Rodríguez, B. L., White, L. R., Yano, K., Curb, J. D., & Abbott, R. D. (1998) · New England Journal of Medicine · doi:10.1056/nejm199801083380204 · Cited by 560
Herbert, B.-S., Pitts, A. E., Baker, S. I., Hamilton, S. E., Wright, W. E., Shay, J. W., & Corey, D. R. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.25.14276 · Cited by 539
Cardiac Stem Cell and Myocyte Aging, Heart Failure, and Insulin-Like Growth Factor-1 Overexpression
Torella, D., Rota, M., Nurzyńska, D., Musso, E., Monsen, A., Shiraishi, I., Zias, E. A., Walsh, K. X., Rosenzweig, A., Sussman, M. A., et al. (2004) · Circulation Research · doi:10.1161/01.res.0000117306.10142.50 · Cited by 538
McMullen, J. R., Shioi, T., Zhang, L., Tarnavski, O., Sherwood, M. C., Kang, P. M., & Izumo, S. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1934654100 · Cited by 534
Kang, P. M., & Izumo, S. (2000) · Circulation Research · doi:10.1161/01.res.86.11.1107 · Cited by 503
Acute doxorubicin cardiotoxicity involves cardiomyocyte apoptosis.
Arola, O., Saraste, A., Pulkki, K. J., Kallajoki, M. A., Parvinen, M., & Voipio-Pulkki, L. M. (2000) · PubMed · Cited by 494
Maack, C., Kartes, T., Kilter, H., Schäfers, H., Nickenig, G., Böhm, M., & Laufs, U. (2003) · Circulation · doi:10.1161/01.cir.0000091084.46500.bb · Cited by 424
Self-citationGoing against the grain: chemotaxis and infection in Vibrio cholerae
Butler, S. M., & Camilli, A. (2005) · Nature Reviews Microbiology · doi:10.1038/nrmicro1207 · Cited by 397
Haendeler, J., Hoffmann, J., Diehl, J. F., Vasa‐Nicotera, M., Spyridopoulos, I., Zeiher, A. M., & Dimmeler, S. (2004) · Circulation Research · doi:10.1161/01.res.0000121104.05977.f3 · Cited by 382
Self-citationPhysical Inactivity Increases Oxidative Stress, Endothelial Dysfunction, and Atherosclerosis
Laufs, U., Wassmann, S., Czech, T., Münzel, T., Eisenhauer, M., Böhm, M., & Nickenig, G. (2005) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.0000158311.24443.af · Cited by 327
Self-citationMechanisms of stroke protection by physical activity
Endres, M., Gertz, K. R., Lindauer, U., Katchanov, J., Schultze, J., Schröck, H., Nickenig, G., Kuschinsky, W., Dirnagl, U., & Laufs, U. (2003) · Annals of Neurology · doi:10.1002/ana.10722 · Cited by 324
Self-citationLeri, A., Franco, S., Zacheo, A., Barlucchi, L., Chimenti, S., Limana, F., Nadal‐Ginard, B., Kajstura, J., Anversa, P., & Blasco, M. A. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg013 · Cited by 313
Krzysztof Reiss, F., Cheng, W. N., Ferbér, A., Kajstura, J., Li, P., Li, B., Olivetti, G., Homcy, C. J., Baserga, R., & Anversa, P. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.16.8630 · Cited by 292
Thum, T., Hoeber, S., Froese, S., Klink, I., Stichtenoth, D. O., Galuppo, P., Jakob, M., Tsikas, D., Anker, S. D., Poole-Wilson, P. A., et al. (2007) · Circulation Research · doi:10.1161/01.res.0000257912.78915.af · Cited by 292
Self-citationOh, H., Taffet, G. E., Youker, K. A., Entman, M. L., Overbeek, P. A., Michael, L. H., & Schneider, M. D. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.191169098 · Cited by 289
Telomere Length of Circulating Leukocytes Is Decreased in Patients With Chronic Heart Failure
van der Harst, P., van der Steege, G., de Boer, R. A., Voors, A. A., Hall, A. S., Mulder, M. J., van Gilst, W. H., & van Veldhuisen, D. J. (2007) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2007.01.027 · Cited by 285
Haendeler, J., Hoffmann, J. U. R., Brandes, R. P., Zeiher, A. M., & Dimmeler, S. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.13.4598-4610.2003 · Cited by 266
Self-citationExercise Training and the Cardiovascular Consequences of Type 2 Diabetes and Hypertension
Stewart, K. J. (2002) · JAMA · doi:10.1001/jama.288.13.1622 · Cited by 257
Gertz, K. R., Priller, J., Kronenberg, G., Fink, K., Winter, B., Schröck, H., Ji, S., Milošević, M., Harms, C., Böhm, M., et al. (2006) · Circulation Research · doi:10.1161/01.res.0000250175.14861.77 · Cited by 252
Self-citationInfluence of Physical Activity on Insulin-Like Growth Factor-I in Healthy Younger and Older Men*
Poehlman, É. T., & Copeland, K. C. (1990) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-71-6-1468 · Cited by 239
Telomere Biology and Cardiovascular Disease
Fuster, J. J., & Andrés, V. (2006) · Circulation Research · doi:10.1161/01.res.0000251281.00845.18 · Cited by 239
Spyridopoulos, I., Haendeler, J., Urbich, C., Brümmendorf, T. H., Oh, H., Schneider, M. D., Zeiher, A. M., & Dimmeler, S. (2004) · Circulation · doi:10.1161/01.cir.0000142866.50300.eb · Cited by 232
Self-citationWege, H. (2002) · Nucleic Acids Research · doi:10.1093/nar/gng003 · Cited by 203
Telomere attrition and Chk2 activation in human heart failure
Oh, H., Wang, S. C., Prahash, A. J. C., Sano, M., Moravec, C. S., Taffet, G. E., Michael, L. H., Youker, K. A., Entman, M. L., & Schneider, M. D. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0836098100 · Cited by 197
Delaughter, M. C., Taffet, G. E., Fiorotto, M. L., Entman, M. L., & Schwartz, R. J. (1999) · The FASEB Journal · doi:10.1096/fasebj.13.14.1923 · Cited by 162
Ascensão, A. A. M. R., Magalhães, J., Soares, J. M. C., Ferreira, R. M., Neuparth, M. J., Marques, F., Oliveira, P. J., & Duarte, J. A. (2005) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.01249.2004 · Cited by 160
Ascensão, A. A. M. R., Ferreira, R. M., & Magalhães, J. (2006) · International Journal of Cardiology · doi:10.1016/j.ijcard.2006.04.076 · Cited by 160
Gensch, C., Clever, Y. P., Werner, C. M., Hanhoun, M., Böhm, M., & Laufs, U. (2006) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2006.06.026 · Cited by 151
Self-citationLow-intensity exercise training during doxorubicin treatment protects against cardiotoxicity
Chicco, A. J., Hydock, D. S., Schneider, C. M., & Hayward, R. (2005) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00148.2005 · Cited by 144
Mice without telomerase: what can they teach us about human cancer?
Artandi, S. E., & DePinho, R. A. (2000) · Nature Medicine · doi:10.1038/78595 · Cited by 126
Aging and the growth hormone/insulin like growth factor-I axis
Sherlock, M., & Toogood, A. A. (2007) · Pituitary · doi:10.1007/s11102-007-0039-5 · Cited by 111
Diastolic Heart Failure in the Elderly
Kitzman, D. W. (2002) · Heart Failure Reviews · doi:10.1023/a:1013745705318 · Cited by 97
Leri, A., Barlucchi, L., Limana, F., Deptała, A., Darżynkiewicz, Z., Hintze, T. H., Kajstura, J., Nadal‐Ginard, B., & Anversa, P. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.151013298 · Cited by 95
Didenko, V. V., Tunstead, J. R., & Hornsby, P. J. (1998) · PubMed · Cited by 70
Short telomeres in aggressive non-Hodgkin's lymphoma as a risk factor in lymphomagenesis
Widmann, T., Herrmann, M., Taha, N., König, J., & Pfreundschuh, M. G. (2007) · Experimental Hematology · doi:10.1016/j.exphem.2007.03.009 · Cited by 64
Self-citationMeasurements of telomere length on individual chromosomes by image cytometry
Poon, S. S. S., & Lansdorp, P. M. (2001) · Methods in cell biology · doi:10.1016/s0091-679x(01)64007-x · Cited by 60
Krzysztof Reiss, F., Cheng, W. N., Pierzchalski, P., Kodali, S., Li, B., Wang, S., Liu, Y., & Anversa, P. (1997) · Experimental Cell Research · doi:10.1006/excr.1997.3669 · Cited by 57
Müller, P., Kazakov, A., Semenov, A., Böhm, M., & Laufs, U. (2007) · Cardiovascular Research · doi:10.1093/cvr/cvm037 · Cited by 51
Self-citationEffects of exercise on longevity of rats.
Holloszy, J. O., & Smith, E. K. (1987) · PubMed · Cited by 29
Research works printed but not linked: 1
- Hornig, 1996, Physical training improves endothelial function in patients with chronic heart failure, Circulation, 93, 210, 10.1161/01.CIR.93.2.210 · DOI
Cited by
Sorted by citations
Exercise Attenuates the Major Hallmarks of Aging
Garatachea, N., Pareja-Galeano, H., Sanchis-Gomar, F., Santos-Lozano, A., Fiuza-Luces, C., Morán, M., Emanuele, E., Joyner, M. J., & Lucia, A. (2015) · Rejuvenation Research · doi:10.1089/rej.2014.1623 · Cited by 413
Physical Exercise Prevents Cellular Senescence in Circulating Leukocytes and in the Vessel Wall
Werner, C., Fürster, T., Widmann, T., Pöss, J., Roggia, C., Hanhoun, M., Scharhag, J., Büchner, N., Meyer, T., Kindermann, W., et al. (2009) · Circulation · doi:10.1161/circulationaha.109.861005 · Cited by 380
Self-citationThe power of exercise: buffering the effect of chronic stress on telomere length
Puterman, E., Lin, J., Blackburn, E., O'Donovan, A., Adler, N., & Epel, E. (2010) · PLoS ONE · doi:10.1371/journal.pone.0010837 · Cited by 339
Loss of cardioprotection with ageing
Boengler, K., Schulz, R., & Heusch, G. (2009) · Cardiovascular Research · doi:10.1093/cvr/cvp033 · Cited by 328
The role of cellular senescence in cardiac disease: basic biology and clinical relevance
Mehdizadeh, M., Aguilar, M., Thorin, E., Ferbeyre, G., & Nattel, S. (2022) · Nature Reviews Cardiology · doi:10.1038/s41569-021-00624-2 · Cited by 304
Metadata
- Authors
- Werner, C., Hanhoun, M., Widmann, T., Kazakov, A., Semenov, A., Pöss, J., Bauersachs, J., Thum, T., Pfreundschuh, M., Müller, P., Haendeler, J., Böhm, M., & Laufs, U.
- Affiliations
- Universitätsklinikum des Saarlandes (DE)
- Universitätsklinikum Würzburg (DE)
- Heinrich Heine University Düsseldorf (DE)
- Corresponding author
- Laufs, Ulrich
- ORCID
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2008-08
- Volume
- 52
- Issue
- 6
- Pages
- 470-482
- ISSN
- 0735-1097 (ISSN-L)
- OpenAlex
- W2055146811
- Cited by
- 239
- References
- 55
- Citations by year
- 2026: 3 · 2025: 12 · 2024: 13 · 2023: 16 · 2022: 14 · 2021: 15 · 2020: 15 · 2019: 12 · 2018: 20 · 2017: 11 · 2016: 16 · 2015: 16 · 2014: 11 · 2013: 10 · 2012: 13
- FWCI
- 9.48
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (KFO-196)
- Universität des Saarlandes
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Effects of Exercise
- Health Sciences › Medicine › Physiology (medical) › Cardiovascular and exercise physiology
- Keywords
- physical activity, telomerase, telomerase reverse transcriptase, endothelial nitric oxide synthase, insulin-like growth factor I, Akt signaling, cardiomyocyte apoptosis, doxorubicin-induced cardiomyopathy, p53, p16, Chk2, cellular senescence, voluntary running, cardioprotection
- MeSH terms
- Animals, Cell Survival, Male, Mice, Inbred C57BL, Motor Activity, Myocardium, Running, Time Factors, Telomere, Cellular Senescence, Apoptosis, Apoptosis Regulatory Proteins, Mice, Nitric Oxide Synthase Type III
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
