Telomere shortening and metabolic compromise underlie dystrophic cardiomyopathy
Open accessAbstract
Significance: We have found that long telomeres protect mice from genetic cardiac diseases analogous to those found in humans, such as Duchenne muscular dystrophy (DMD). Mice lacking dystrophin, similar to patients with DMD, exhibit only mild disease. In contrast, mice that lack dystrophin and have “humanized” telomere lengths ( mdx 4cv /mTR G2 ) fully manifest both the severe human skeletal muscle wasting and cardiac failure typical of DMD. Remarkably, telomere shortening accompanies cardiac development even after cardiomyocyte division has ceased. This chronic proliferation-independent shortening in dystrophin-deficient cardiomyocytes is associated with induction of a DNA damage response, mitochondrial dysfunction, increased oxidative stress, and metabolic failure. Our findings highlight an interplay between telomere length and mitochondrial homeostasis in the etiology of dystrophic heart failure.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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 mouse models of accelerated telomere shortening, critically short telomeres repress PGC1-α- and β-mediated mitochondrial biogenesis.
“In mouse models of accelerated telomere shortening, critically short telomeres have been shown to repress PGC1‐α‐ and β‐mediated mitochondrial biogenesis (Sahin et al, 2011; Chang et al, 2016).”
From Length-independent telomere damage drives post-mitotic cardiomyocyte senescence (2019) · cites this paper as Chang et al, 2016
Mouse models of accelerated telomere shortening exhibit cardiac dysfunction.
“Short telomeres have been observed in aged murine CMs (Rota et al, 2007) and in cardiomyocytes from individuals with end‐stage hypertrophic or dilated cardiomyopathy (Chang et al, 2018) and mouse models of accelerated telomere shortening exhibit cardiac dysfunction (Chang et al, 2016).”
From Length-independent telomere damage drives post-mitotic cardiomyocyte senescence (2019) · cites this paper as Chang et al, 2016
Cites
DAVID: Database for Annotation, Visualization, and Integrated Discovery
Dennis, G., Sherman, B. T., Hosack, D. A., Yang, J., Gao, W., Lane, H. C., & Lempicki, R. A. (2003) · Genome Biology · doi:10.1186/gb-2003-4-5-p3 · Cited by 9,327 · see citing works
Mdm2 promotes the rapid degradation of p53
Haupt, Y., Maya, R., Kazaz, A., & Oren, M. (1997) · Nature · doi:10.1038/387296a0 · Cited by 4,506 · see citing works
Evidence for Cardiomyocyte Renewal in Humans
Bergmann, O., Bhardwaj, R. D., Bernard, S., Zdunek, S., Barnabé-Heider, F., Walsh, S., Zupicich, J., Alkass, K., Buchholz, B. A., Druid, H., et al. (2009) · Science · doi:10.1126/science.1164680 · Cited by 3,130 · see citing works
Shelterin: the protein complex that shapes and safeguards human telomeres
de Lange, T. (2005) · Genes & Development · doi:10.1101/gad.1346005 · Cited by 3,056 · see citing works
Koenig, M., Hoffman, E. P., Bertelson, C. J., Monaco, A. P., Feener, C., & Kunkel, L. M. (1987) · Cell · doi:10.1016/0092-8674(87)90504-6 · Cited by 2,411 · see citing works
Telomere Shortening and Tumor Formation by Mouse Cells Lacking Telomerase RNA
Blasco, M. A., Lee, H.-W., Hande, M. P., Samper, E., Lansdorp, P. M., DePinho, R. A., & Greider, C. W. (1997) · Cell · doi:10.1016/s0092-8674(01)80006-4 · Cited by 2,108 · see citing works
X chromosome-linked muscular dystrophy (mdx) in the mouse
Bulfield, G., Siller, W. G., Wight, P. A., & Moore, K. J. (1984) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.81.4.1189 · Cited by 1,765 · see citing works
Blackburn, E. H., Epel, E. S., & Lin, J. (2015) · Science · doi:10.1126/science.aab3389 · Cited by 1,596 · see citing works
Telomere dysfunction induces metabolic and mitochondrial compromise
Sahin, E., Colla, S., Liesa, M., Moslehi, J., Müller, F. L., Guo, M., Cooper, M., Kotton, D., Fabian, A. J., Walkey, C., et al. (2011) · Nature · doi:10.1038/nature09787 · Cited by 1,319 · see citing works
Essential role of mouse telomerase in highly proliferative organs
Lee, H.-W., Blasco, M. A., Gottlieb, G. J., Horner, J. W., Greider, C. W., & DePinho, R. A. (1998) · Nature · doi:10.1038/33345 · Cited by 1,270 · cited 1× · see citing works
“G2 is well before the telomere shortening observed ubiquitously in mTR mice with successive generations, which by G4 mimic an aging phenotype (18).”
BackgroundRapid Transition of Cardiac Myocytes from Hyperplasia to Hypertrophy During Postnatal Development
Li, F. (1996) · Journal of Molecular and Cellular Cardiology · doi:10.1006/jmcc.1996.0163 · Cited by 837 · see citing works
MicroRNA-34a regulates cardiac ageing and function.
Boon, R. A., Iekushi, K., Lechner, S., Seeger, T., Fischer, A., Heydt, S., Kaluza, D., Tréguer, K., Carmona, G., Bonauer, A., et al. (2013) · Nature · doi:10.1038/nature11919 · Cited by 821 · see citing works
Cardiomyocyte DNA synthesis and binucleation during murine development
Soonpaa, M. H., Kim, K. K., Pajak, L., Franklin, M. T., & Field, L. J. (1996) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1996.271.5.h2183 · Cited by 718 · see citing works
Dystrophin expression in muscle stem cells regulates their polarity and asymmetric division
Dumont, N. A., Wang, Y. X., von Maltzahn, J., Pasut, A., Bentzinger, C. F., Brun, C. E., & Rudnicki, M. A. (2015) · Nature Medicine · doi:10.1038/nm.3990 · Cited by 616 · see citing works
X-ROS Signaling: Rapid Mechano-Chemo Transduction in Heart
Prosser, B. L., Ward, C. W., & Lederer, W. J. (2011) · Science · doi:10.1126/science.1202768 · Cited by 564 · see citing works
Short Telomeres and Stem Cell Exhaustion Model Duchenne Muscular Dystrophy in mdx/mTR Mice
Sacco, A., Mourkioti, F., Tran, R., Choi, J., Llewellyn, M., Kraft, P., Shkreli, M., Delp, S., Pomerantz, J. H., Artandi, S. E., et al. (2010) · Cell · doi:10.1016/j.cell.2010.11.039 · Cited by 512 · see citing works
Self-citationMitochondrial Fusion is Essential for Organelle Function and Cardiac Homeostasis
Chen, Y., Liu, Y., & Dorn, G. W. (2011) · Circulation Research · doi:10.1161/circresaha.111.258723 · Cited by 506 · see citing works
Cardiomyocyte Cell Cycle Regulation
Pasumarthi, K. B. S., & Field, L. J. (2002) · Circulation Research · doi:10.1161/01.res.0000020201.44772.67 · Cited by 469 · see citing works
Defective myoblasts identified in Duchenne muscular dystrophy
Blau, H. M., Webster, C., & Pavlath, G. K. (1983) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.80.15.4856 · Cited by 335 · see citing works
Self-citationContemporary Cardiac Issues in Duchenne Muscular Dystrophy
McNally, E. M., Kaltman, J. R., Benson, D. W., Canter, C. E., Cripe, L. H., Duan, D., Finder, J. D., Groh, W. J., Hoffman, E. P., Judge, D. P., et al. (2015) · Circulation · doi:10.1161/circulationaha.114.015151 · Cited by 326 · see citing works
Conservation of the Duchenne Muscular Dystrophy Gene in Mice and Humans
Hoffman, E. P., Monaco, A. P., Feener, C. A., & Kunkel, L. M. (1987) · Science · doi:10.1126/science.3659917 · Cited by 259 · see citing works
Recovery of induced mutations for X chromosome-linked muscular dystrophy in mice.
Chapman, V. M., Miller, D. R., Armstrong, D., & Caskey, C. T. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.4.1292 · Cited by 227 · see citing works
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 · see citing works
The role of PGC-1α on mitochondrial function and apoptotic susceptibility in muscle
Adhihetty, P. J., Uguccioni, G., Leick, L., Hidalgo, J., Pilegaard, H., & Hood, D. A. (2009) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00070.2009 · Cited by 168 · see citing works
Chang, A. C. Y., Fu, Y., Garside, V. C., Niessen, K. S., Chang, L., Fuller, M. E., Setiadi, A., Smrz, J., Kyle, A. H., Minchinton, A. I., et al. (2011) · Developmental Cell · doi:10.1016/j.devcel.2011.06.022 · Cited by 164 · see citing works
Self-citationAccelerated Telomere Shortening in Fibroblasts After Extended Periods of Confluency
Sitte, N. (1998) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(97)00363-8 · Cited by 162 · see citing works
Bär, C., de Jesus, B. B., Serrano, R., Tejera, A., Ayuso, E., Jimenez, V., Formentini, I., Bobadilla, M., Mizrahi, J., de Martino, A., et al. (2014) · Nature Communications · doi:10.1038/ncomms6863 · Cited by 162 · see citing works
Animal models for muscular dystrophy: valuable tools for the development of therapies
Allamand, V. (2000) · Human Molecular Genetics · doi:10.1093/hmg/9.16.2459 · Cited by 150 · see citing works
Mice with bad ends: mouse models for the study of telomeres and telomerase in cancer and aging
Blasco, M. A. (2005) · The EMBO Journal · doi:10.1038/sj.emboj.7600598 · Cited by 147 · see citing works
Role of telomere dysfunction in cardiac failure in Duchenne muscular dystrophy
Mourkioti, F., Kustan, J., Kraft, P. E., Day, J., Zhao, M., Kost‐Alimova, M., Protopopov, A. I., DePinho, R. A., Bernstein, D., Meeker, A. K., et al. (2013) · Nature Cell Biology · doi:10.1038/ncb2790 · Cited by 136 · see citing works
Self-citationMavrogeni, S. I., Papavasiliou, A., Spargias, K., Constandoulakis, P., Papadopoulos, G., Karanasios, E., Georgakopoulos, D., Kolovou, G. D., Demerouti, E., Polymeros, S., et al. (2010) · BMC Neurology · doi:10.1186/1471-2377-10-33 · Cited by 90 · see citing works
Association of telomere shortening in myocardium with heart weight gain and cause of death
Terai, M., Izumiyama‐Shimomura, N., Aida, J., Ishikawa, N., Sawabe, M., Arai, T., Fujiwara, M., Ishii, A., Nakamura, K., & Takubo, K. (2013) · Scientific Reports · doi:10.1038/srep02401 · Cited by 46 · see citing works
Guzzardi, M. A., Iozzo, P., Salonen, M. K., Kajantie, E., & Eriksson, J. G. (2015) · Annals of Medicine · doi:10.3109/07853890.2015.1074718 · Cited by 33 · see citing works
Evdokimovsky, E. V., Ushakova, T. E., Kudriavtcev, A. A., & Gaziev, A. I. (2011) · Radiation and Environmental Biophysics · doi:10.1007/s00411-010-0329-6 · Cited by 28 · see citing works
Duchenne and Becker Muscular Dystrophies: Genetics, Prenatal Diagnosis, and Future Prospects
Bieber, F. R., & Hoffman, E. P. (1990) · Clinics in Perinatology · doi:10.1016/s0095-5108(18)30549-9 · Cited by 24 · see citing works
Sb, C., Pj, V., & Watkins, M. (1966) · PubMed · Cited by 13 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The impact of oxidative DNA damage and stress on telomere homeostasis
Barnes, R. P., Fouquerel, E., & Opresko, P. L. (2018) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2018.03.013 · Cited by 558 · see citing works
Length-independent telomere damage drives post-mitotic cardiomyocyte senescence
Anderson, R., Lagnado, A., Maggiorani, D., Walaszczyk, A., Dookun, E., Chapman, J., Birch, J., Salmonowicz, H., Ogrodnik, M., Jurk, D., et al. (2019) · The EMBO Journal · doi:10.15252/embj.2018100492 · Cited by 532 · see citing works
“In the mdx 4cv / mTR G2 mouse model of telomere dysfunction, reduced expression of shelterin components is suggested to underlie increased telomere erosion in CMs (Mourkioti et al , 2013; Chang et al , 2016).”
Senescence mechanisms and targets in the heart
Chen, M. S., Lee, R. T., & Garbern, J. C. (2021) · Cardiovascular Research · doi:10.1093/cvr/cvab161 · Cited by 336 · see citing works
Telomere Dysfunction Induces Sirtuin Repression that Drives Telomere-Dependent Disease
Amano, H., Chaudhury, A., Rodriguez-Aguayo, C., Lu, L., Akhanov, V., Catic, A., Popov, Y. V., Verdin, E., Johnson, H., Stossi, F., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.03.001 · Cited by 182 · see citing works
Cardiac ageing: extrinsic and intrinsic factors in cellular renewal and senescence
Gude, N. A., Broughton, K. M., Firouzi, F., & Sussman, M. A. (2018) · Nature Reviews Cardiology · doi:10.1038/s41569-018-0061-5 · Cited by 166 · see citing works
Telomeres, Telomerase and Ageing
Saretzki, G. C. (2018) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-981-13-2835-0_9 · Cited by 114 · see citing works
Telomere shortening is a hallmark of genetic cardiomyopathies
Chang, A. C. Y., Chang, A. C. H., Kirillova, A., Sasagawa, K., Su, W., Weber, G., Lin, J., Termglinchan, V., Karakikes, I., Seeger, T., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1714538115 · Cited by 91 · see citing works
Self-citationCasagrande, S., Stier, A., Monaghan, P., Loveland, J. L., Boner, W., Lupi, S., Trevisi, R., & Hau, M. (2020) · Journal of Experimental Biology · doi:10.1242/jeb.222513 · Cited by 85 · see citing works
Cardiac Aging: From Basic Research to Therapeutics
Yan, M.-J., Sun, S.-H., Xu, K., Huang, X.-Q., Dou, L., Pang, J., Tang, W.-Q., Shen, T., & Li, J. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/9570325 · Cited by 77 · see citing works
Trends in tissue repair and regeneration
Galliot, B., Crescenzi, M., Jacinto, A., & Tajbakhsh, S. (2017) · Development · doi:10.1242/dev.144279 · Cited by 81 · see citing works
Zhang, A., Liu, Y., Pan, J., Pontanari, F., Chang, A. C. H., Wang, H., Gao, S., Wang, C., & Chang, A. C. Y. (2023) · Molecular Therapy · doi:10.1016/j.ymthe.2023.02.016 · Cited by 77 · see citing works
Self-citationMouse models for muscular dystrophies: an overview
van Putten, M., Lloyd, E. M., de Greef, J. C., Raz, V., Willmann, R., & Grounds, M. D. (2020) · Disease Models & Mechanisms · doi:10.1242/dmm.043562 · Cited by 62 · see citing works
Telomere function and regulation from mouse models to human ageing and disease
Jones-Weinert, C. W., Mainz, L., & Karlseder, J. (2024) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-024-00800-5 · Cited by 57 · see citing works
Chang, A. C. Y., Pardon, G., Chang, A. C. H., Wu, H., Ong, S., Eguchi, A., Ancel, S., Holbrook, C., Ramunas, J., Ribeiro, A. J. S., et al. (2021) · Stem Cell Reports · doi:10.1016/j.stemcr.2021.04.018 · Cited by 52 · see citing works
Self-citationMitochondrial function in skeletal myofibers is controlled by a TRF2‐SIRT3 axis over lifetime
Robin, J. D., Burbano, M. S. J., Peng, H., Croce, O., Thomas, J. L., Laberthonnìère, C., Renault, V. M., Lototska, L., Pousse, M., Tessier, F., et al. (2020) · Aging Cell · doi:10.1111/acel.13097 · Cited by 51 · see citing works
Rebalancing expression of HMGB1 redox isoforms to counteract muscular dystrophy
Careccia, G., Saclier, M., Tirone, M., Ruggieri, E., Principi, E., Raffaghello, L., Torchio, S., Recchia, D., Canepari, M., Gorzanelli, A., et al. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.aay8416 · Cited by 51 · see citing works
Therapeutic opportunities for senolysis in cardiovascular disease
Sweeney, M. D., Cook, S. A., & Gil, J. (2022) · FEBS Journal · doi:10.1111/febs.16351 · Cited by 51 · see citing works
Signorelli, M., Ayoglu, B., Johansson, C., Lochmüller, H., Straub, V. W., Francesco Muntoni, A., Niks, E. H., Tsonaka, R., Persson, A. B., Aartsma-Rus, A. M., et al. (2019) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.12517 · Cited by 51 · see citing works
Hughes, M. C., Ramos, S. V., Turnbull, P. C., Edgett, B. A., Huber, J. S., Polidovitch, N., Schlattner, U., Backx, P. H., Simpson, J. A., & Perry, C. G. R. (2019) · The Journal of Physiology · doi:10.1113/jp277306 · Cited by 42 · see citing works
The Duchenne muscular dystrophy gene and cancer
Jones, L., Naidoo, M. D. E., Machado, L. R., & Anthony, K. (2020) · Cellular Oncology · doi:10.1007/s13402-020-00572-y · Cited by 49 · see citing works
Cai, Y., Kandula, V., Kosuru, R., Ye, X., Irwin, M. G., & Xia, Z. (2017) · Cell Cycle · doi:10.1080/15384101.2017.1371886 · Cited by 44 · see citing works
Brandt, M., Doerschmann, H., Khraisat, S., Knopp, T., Ringen, J., Kalinovic, S., Garlapati, V. S., Siemer, S., Molitor, M., Göbel, S., et al. (2022) · Hypertension · doi:10.1161/hypertensionaha.121.18935 · Cited by 45 · see citing works
Exosomes exert cardioprotection in dystrophin-deficient cardiomyocytes via ERK1/2-p38/MAPK signaling
Gartz, M., Darlington, A. M., Afzal, M. Z., & Strande, J. L. (2018) · Scientific Reports · doi:10.1038/s41598-018-34879-6 · Cited by 43 · see citing works
Dubinin, M. V., Talanov, E. Y., Tenkov, K. S., Starinets, V. S., Mikheeva, I. B., & Belosludtsev, K. N. (2020) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2020.148250 · Cited by 44 · see citing works
p53‐Dependent Mitochondrial Compensation in Heart Failure With Preserved Ejection Fraction
Chen, X., Lin, H., Xiong, W., Pan, J., Huang, S., Xu, S., He, S., Lei, M., Chang, A. C. Y., & Zhang, H. (2022) · Journal of the American Heart Association · doi:10.1161/jaha.121.024582 · Cited by 38 · see citing works
Self-citationPentraxin 3: A promising therapeutic target for cardiovascular diseases
Ye, X., Wang, Z., Lei, W., Shen, M., Tang, J., Xu, X., Yang, Y., & Zhang, H. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.102163 · Cited by 33 · see citing works
Oxidative Stress and DNA Damage at Telomeres
Opresko, P. L., Sanford, S. L., & De Rosa, M. (2025) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a041707 · Cited by 30 · see citing works
Sesillo, F. B., Fox, D. J., & Sacco, A. (2019) · Cell Reports · doi:10.1016/j.celrep.2018.12.089 · Cited by 26 · see citing works
Loss of the long non-coding RNA OIP5-AS1 exacerbates heart failure in a sex-specific manner
Zhuang, A., Calkin, A. C., Lau, S., Kiriazis, H., Donner, D. G., Liu, Y., Bond, S. T., Moody, S. C., Gould, E. A. M., Colgan, T. D., et al. (2021) · iScience · doi:10.1016/j.isci.2021.102537 · Cited by 24 · see citing works
The role of cardiomyocyte senescence in cardiovascular diseases: a molecular biology update.
He, S., Yan, L., Yuan, C., Li, W., Wu, T., Chen, S., Li, N., Wu, M., & Jiang, J. (2024) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2024.176961 · Cited by 19 · see citing works
Eguchi, A., Gonzalez, A. F. G. S., Torres-Bigio, S. I., Koleckar, K., Birnbaum, F., Zhang, J. Z., Wang, V. Y., Wu, J. C., Artandi, S. E., & Blau, H. M. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2209967120 · Cited by 22 · see citing works
Self-citationDMD-Associated Dilated Cardiomyopathy: Genotypes, Phenotypes, and Phenocopies
Johnson, R., Otway, R., Chin, E. L. H., Horvat, C., Ohanian, M., Wilcox, J. A., Su, Z., Prestes, P. R., Smolnikov, A., Soka, M. J., et al. (2023) · Circulation Genomic and Precision Medicine · doi:10.1161/circgen.123.004221 · Cited by 23 · see citing works
Self-citationLi, B., Xiong, W., Zuo, W., Shi, Y., Wang, T., Chang, L., Wu, Y., Ma, H., Bian, Q., & Chang, A. C. Y. (2024) · Nucleic Acids Research · doi:10.1093/nar/gkae274 · Cited by 22 · see citing works
Self-citationDystrophic Cardiomyopathy: Complex Pathobiological Processes to Generate Clinical Phenotype
Tsuda, T., & Fitzgerald, K. K. (2017) · Journal of Cardiovascular Development and Disease · doi:10.3390/jcdd4030014 · Cited by 22 · see citing works
Long-lived post-mitotic cell aging: is a telomere clock at play?
Burbano, M. S. J., & Gilson, É. (2020) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2020.111256 · Cited by 18 · see citing works
Context matters – Daxx and Atrx are not robust tumor suppressors in the murine endocrine pancreas
Sun, C., Estrella, J. S., Whitley, E. M., Chau, G. P., Lozano, G., & Wasylishen, A. R. (2022) · Disease Models & Mechanisms · doi:10.1242/dmm.049552 · Cited by 20 · see citing works
TECRL deficiency results in aberrant mitochondrial function in cardiomyocytes
Hou, C., Jiang, X., Zhang, H., Zheng, J., Qiu, Q., Zhang, Y., Sun, X., Xu, M., Chang, A. C. Y., Xie, L., et al. (2022) · Communications Biology · doi:10.1038/s42003-022-03414-9 · Cited by 19 · see citing works
Self-citationhnRNPA2 mediated acetylation reduces telomere length in response to mitochondrial dysfunction
Guha, M., Srinivasan, S., Johnson, F. B., Ruthel, G. T., Guja, K. E., García–Díaz, M., Kaufman, B. A., Glineburg, M. R., Fang, J.-K., Nakagawa, H., et al. (2018) · PLoS ONE · doi:10.1371/journal.pone.0206897 · Cited by 18 · see citing works
Birnbaum, F., Eguchi, A., Pardon, G., Chang, A. C. Y., & Blau, H. M. (2022) · npj Regenerative Medicine · doi:10.1038/s41536-022-00214-x · Cited by 17 · see citing works
Self-citationWilli, L., Abramovich, I., Fernández-García, J., Agranovich, B., Shulman, M., Milman, H., Baskin, P., Eisen, B., Michele, D. E., Arad, M., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23179808 · Cited by 15 · see citing works
Dowling, P., Gargan, S., Zweyer, M., Swandulla, D., & Ohlendieck, K. (2023) · Biomolecules · doi:10.3390/biom13071108 · Cited by 15 · see citing works
Ryanodine receptor dysfunction causes senescence and fibrosis in Duchenne dilated cardiomyopathy
Souidi, M., Resta, J., Dridi, H., Sleiman, Y., Reiken, S. R., Formoso, K., Colombani, S., Amédro, P., Meyer, P., Charrabi, A., et al. (2024) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.13411 · Cited by 15 · see citing works
Muscular dystrophy: Experimental animal models and therapeutic approaches (Review)
Gaina, G. F., & (Gruianu), A. P. (2021) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2021.10042 · Cited by 15 · see citing works
Short telomeres — A hallmark of heritable cardiomyopathies
Chang, A. C. Y., & Blau, H. M. (2018) · Differentiation · doi:10.1016/j.diff.2018.02.001 · Cited by 14 · see citing works
Self-citationPeng, T., Xiang, J., Tian, Y., Tang, X., Wang, L., Gao, L., Luo, O. J., Huang, L., & Chen, G. (2025) · Experimental Gerontology · doi:10.1016/j.exger.2025.112686 · Cited by 13 · see citing works
Soussi, S., Savchenko, L., Rovina, D., Iacovoni, J. S., Gottinger, A., Vialettes, M., Pioner, J. M., Farini, A., Mallia, S., Rabino, M., et al. (2023) · Biology Direct · doi:10.1186/s13062-023-00398-2 · Cited by 12 · see citing works
Shen, Q., Wu, J., Ni, Y., Xie, X., Yu, C., Xiao, Q., Zhou, J., Wang, X., & Fu, Z. (2019) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gmz070 · Cited by 12 · see citing works
Self-citationQiu, G., Zheng, X., Fu, M., Huang, C., & Yang, X. (2019) · Biogerontology · doi:10.1007/s10522-019-09832-3 · Cited by 12 · see citing works
Hassanpour, H., Farhadi, N., Bahadoran, S., & Akbari, M. R. (2023) · British Poultry Science · doi:10.1080/00071668.2022.2163877 · Cited by 9 · see citing works
Łoboda, A., & Dulak, J. (2024) · Cells · doi:10.3390/cells13020158 · Cited by 9 · see citing works
Obal, D., & Wu, J. C. (2020) · British Journal of Pharmacology · doi:10.1111/bph.15228 · Cited by 8 · see citing works
Self-citationCasagrande, S., Loveland, J. L., Oefele, M., Boner, W., Lupi, S., Stier, A., & Hau, M. (2023) · Molecular Ecology · doi:10.1111/mec.17114 · Cited by 8 · see citing works
Liu, C., Lin, K., Xie, Z., Li, D., Fan, J. J., Chen, Y., Gao, S., Wang, X., Liu, N., Xue, Q., et al. (2024) · Frontiers in Bioscience-Landmark · doi:10.31083/j.fbl2907263 · Cited by 7 · see citing works
Hayes, H. M., Angerosa, J., Piers, A. T., White, J. D., Koleff, J., Thurgood, M., Moody, J., Cheung, M. M. H., & Pepe, S. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/5362115 · Cited by 7 · see citing works
Barker, R. G., van der Poel, C., Horvath, D., & Murphy, R. M. (2018) · Sports · doi:10.3390/sports6040109 · Cited by 7 · see citing works
Have Duchenne Muscular Dystrophy Patients an Increased Cancer Risk?
Vita, G. L., Politano, L., Berardinelli, A. L., & Vita, G. (2021) · Journal of Neuromuscular Diseases · doi:10.3233/jnd-210676 · Cited by 7 · see citing works
DNA damage and repair in cardiomyopathy: mechanisms and therapeutic opportunities
Zhou, X., Yu, Z., Chen, Z., Evans, S. Μ., & Chen, J. (2025) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00774.2025 · Cited by 6 · see citing works
Leukocyte telomere length in patients with myotonic dystrophy type I: a pilot study
Wang, Y., Best, A. F., Fernández‐Torrón, R., Alsaggaf, R., García-Puga, M., Dagnall, C. L., Hicks, B. D., Thompson, M. B., Matheu, A., Zulaica, M., et al. (2019) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.50954 · Cited by 6 · see citing works
Targeting of CAT and VCAM1 as Novel Therapeutic Targets for DMD Cardiomyopathy
Li, B., Xiong, W., Liang, W., Chiou, J., Lin, Y.-J., & Chang, A. C. Y. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.659177 · Cited by 6 · see citing works
Self-citationRalston, E., Gutierrez-Cruz, G., Kenea, A., & Brooks, S. R. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.07.16.452553 · Cited by 6 · see citing works
Cellular senescence in age-related cardiovascular disease: past and future
Wu, X., Zhou, Q. S., Huang, Y., Jiang, W., Zhou, J., Qian, K., Pan, Y. P., Wu, Z., Zhang, J., Aimaiti, M., et al. (2026) · Frontiers in Aging · doi:10.3389/fragi.2025.1721744 · Cited by 5 · see citing works
Rubromycins: A Class of Telomerase Inhibitor Antibiotics Produced by Streptomyces spp.
Boumehira, A. Z., Hacène, H., & Enshasy, H. A. E. (2019) · Elsevier eBooks · doi:10.1016/b978-0-444-63504-4.00011-6 · Cited by 4 · see citing works
Gheytaspour, P., Bahadoran, S., & Hassanpour, H. (2025) · Veterinary Medicine and Science · doi:10.1002/vms3.70355 · Cited by 3 · see citing works
Cozzolino, M., Ergun, Y., Ristori, E., Garg, A., Imamoglu, G., & Seli, E. U. (2024) · Aging · doi:10.18632/aging.205543 · Cited by 2 · see citing works
MKT-077 normalizes mitochondrial function and mitigates cardiac pathology in mdx mice
Stepanova, A. E., Mikina, N. V., SUSHENTSOV, D. V., Sharapov, V. A., Cherepanova, A. A., Loskutov, V. V., Dubinin, M. V., Belosludtsev, K. N., & Mikheeva, I. B. (2024) · Biocell · doi:10.32604/biocell.2024.058068 · Cited by 2 · see citing works
Exploring new therapeutics for Duchenne muscular dystrophy and related cardiomyopathy
Li, B., Xiong, W., Chang, A. C. H., & Chang, A. C. Y. (2025) · Rare Disease and Orphan Drugs Journal · doi:10.20517/rdodj.2024.44 · Cited by 1 · see citing works
Self-citationMechanisms 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 · see citing works
Telomere shortening in laminopathic dilated cardiomyopathy
Chang, A. C. Y., Pardon, G., Chang, A. C.-H., Wang, C., Termglinchan, V., Кіріллова, А., Nicin, L., Birnbaum, F., Laquerrière, A., Bonne, G., et al. (2026) · npj Regenerative Medicine · doi:10.1038/s41536-026-00462-1 · Cited by 1 · see citing works
Self-citationBehrmann, A. J., Cayton, J., Hayden, M. R., Lambert, M. D., Nourian, Z., Nyanyo, K., Godbee, B., Hanft, L. M., Krenz, M., McDonald, K. S., et al. (2024) · Physiological Reports · doi:10.14814/phy2.16004 · Cited by 1 · see citing works
Ahmed, F. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1715373114
Velmurugan, K. R. (2017) · VTechWorks (Virginia Tech)
A Novel Mice Model of Catecholaminergic Polymorphic Ventricular Tachycardia Generated by CRISPR/Cas9Preprint
Hou, C., Jiang, X., Qiu, Q., Zheng, J., Lin, S., Chen, S., Xu, M. J., Zhang, Y., Xie, L., & Xiao, T. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.10.14.464343
Soussi, S., Савченко, Л. В., Rovina, D., Iacovoni, J. S., Gottinger, A., Vialettes, M., Pioner, J.-M., Farini, A., Mallia, S., Rabino, M., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26606866
Modified hTERT treatment ameliorates pressure overload-induced heart failure
Zhao, Y., Bao, X., Xiong, W., Wan, X., Yu, Q., Wang, T., Chang, A. C. H., Liu, Y., Wang, Y., Shang, C., et al. (2026) · EBioMedicine · doi:10.1016/j.ebiom.2026.106203
Self-citationCaractérisation de la sénescence des cardiomyocytes et identification de marqueurs associés
Maggiorani, D. (2017) · theses.fr (ABES) · doi:10.70675/a58747bczd60bz4482za3b2z7ae33d26ffa4
Telomere recapping prevents pathogenic telomere-to-mitochondrial DNA communication in heart failure
Zhao, Y., Bao, X., Xiong, W., Wan, X., Yu, Q., Wang, T., Chang, A. C. H., Zhang, A., Zhang, P., Lin, Z., et al. (2026) · Cardiovascular Research · doi:10.1093/cvr/cvag077
Self-citationYao, Y., & Gao, Y. (2026) · Hemodynamics · doi:10.1097/hd9.0000000000000026
Duchenne muscular dystrophy: from gene to gene-ius therapies
Muchir, A., Musarò, A., & Chamberlain, J. S. (2026) · Skeletal Muscle · doi:10.1186/s13395-026-00439-0
Bevington, R. T., Johnson, A., Hockey, B. L., Fajardo, V. A., & Parise, G. (2026) · Aging Cell · doi:10.1111/acel.70759
- Authors
- Chang, A. C. Y., Ong, S.-G., LaGory, E. L., Kraft, P. E., Giaccia, A. J., Wu, J. C., & Blau, H. M.
- Affiliations
- Stanford Medicine (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2016-10-31
- Volume
- 113
- Issue
- 46
- Pages
- 13120-13125
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC5135315
- OpenAlex
- W2543485777
- Cited by
- 81
- References
- 36
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 10 · 2023: 9 · 2022: 8 · 2021: 10 · 2020: 8 · 2019: 9 · 2018: 8 · 2017: 6
- FWCI
- 6.17
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- California Institute for Regenerative Medicine (TT3-05501, RB5-07469)
- HHS | National Institutes of Health (AG044815, AG009521, NS089533, AR063963, AG020961)
- Gouvernement du Canada | Canadian Institutes of Health Research (201411MFE-338745-169197)
- American Heart Association (13POST14480004, 15POST22940013)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiomyopathy and Myosin Studies
- Keywords
- dystrophic cardiomyopathy, dilated cardiomyopathy, Duchenne muscular dystrophy, telomere shortening, DNA damage response, p53, p21, mitochondrial biogenesis, oxidative stress, mitochondrial membrane potential, heart failure
- MeSH terms
- Animals, Cardiomyopathy, Dilated, Cell Cycle, DNA Damage, Male, Mice, Inbred C57BL, Mitochondria, Heart, Mitosis, Muscular Dystrophy, Animal, Reactive Oxygen Species, Mice, Knockout, Muscular Dystrophy, Duchenne, Myocytes, Cardiac, Cell Proliferation, Membrane Potential, Mitochondrial, Telomere Shortening
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
