Comparative biology of mammalian telomeres: hypotheses on ancestral states and the roles of telomeres in longevity determination
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Summary: Progressive telomere shortening from cell division (replicative aging) provides a barrier for human tumor progression. This program is not conserved in laboratory mice, which have longer telomeres and constitutive telomerase. Wild species that do/do not use replicative aging have been reported, but the evolution of different phenotypes and a conceptual framework for understanding their uses of telomeres is lacking. We examined telomeres/telomerase in cultured cells from > 60 mammalian species to place different uses of telomeres in a broad mammalian context. Phylogeny‐based statistical analysis reconstructed ancestral states. Our analysis suggested that the ancestral mammalian phenotype included short telomeres (< 20 kb, as we now see in humans) and repressed telomerase. We argue that the repressed telomerase was a response to a higher mutation load brought on by the evolution of homeothermy. With telomerase repressed, we then see the evolution of replicative aging. Telomere length inversely correlated with lifespan, while telomerase expression co‐evolved with body size. Multiple independent times smaller, shorter‐lived species changed to having longer telomeres and expressing telomerase. Trade‐offs involving reducing the energetic/cellular costs of specific oxidative protection mechanisms (needed to protect < 20 kb telomeres in the absence of telomerase) could explain this abandonment of replicative aging. These observations provide a conceptual framework for understanding different uses of telomeres in mammals, support a role for human‐like telomeres in allowing longer lifespans to evolve, demonstrate the need to include telomere length in the analysis of comparative studies of oxidative protection in the biology of aging, and identify which mammals can be used as appropriate model organisms for the study of the role of telomeres in human cancer and aging.
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The programmed silencing of TERT, loss of telomerase activity, and telomere shortening is not universal in mammals; it appears restricted to large animals with long lifespan.
“The programmed silencing of TERT, loss of telomerase activity and the resulting shortening of telomeres is not a universal phenomenon in mammals. Apparently, this tumour suppressor pathway is restricted to large animals with a reproductive strategy that requires a long lifespan28.”
From Telomeres in cancer: tumour suppression and genome instability (2017) · cites this paper as [28]
The evolution of large body sizes and longevity is strongly associated with the evolution of short telomeres and telomerase suppression, presumably for tumour suppression.
“Taken together, it seems that the evolution of large body sizes and longevity is strongly associated with the evolution of short telomeres and telomerase suppression, presumably for tumour suppression (de Magalhaes, 2013; Gomes et al., 2011).”
From Stress, cell senescence and organismal ageing (2018) · cites this paper as Gomes et al., 2011
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Cites
Aging: a theory based on free radical and radiation chemistry
Harman, D. (1956) · Journal of Gerontology · doi:10.1093/geronj/11.3.298 · Cited by 8,567 · see citing works
Friedberg, E. C., Walker, G. C., Siede, W., Wood, R. D., Schultz, R. A., & Ellenberger, T. (2005) · doi:10.1128/9781555816704 · Cited by 5,683 · see citing works
Inferring the historical patterns of biological evolution
Pagel, M. (1999) · Nature · doi:10.1038/44766 · Cited by 5,200 · see citing works
Self-citationA survey of telomerase activity in human cancer
Shay, J. W., & Bacchetti, S. (1997) · European Journal of Cancer · doi:10.1016/s0959-8049(97)00062-2 · Cited by 2,794 · see citing works
Self-citationCellular Scaling Rules for the Brains of Marsupials: Not as “Primitive” as Expected
Santos, S. E. D., Porfírio, J., Cunha, F., Manger, P. R., Tavares, W. C., Pessôa, L. M., Raghanti, M. A., Sherwood, C. C., & Herculano‐Houzel, S. (2017) · Brain Behavior and Evolution · doi:10.1159/000452856 · Cited by 2,651 · see citing works
Phylogenetic Analysis and Comparative Data: A Test and Review of Evidence
Freckleton, R. P., Harvey, P. H., & Pagel, M. (2002) · The American Naturalist · doi:10.1086/343873 · Cited by 2,604 · see citing works
Self-citationMoyzis, R. K., Buckingham, J. M., Cram, L. S., Dani, M. A. C., Deaven, L. L., Jones, M. D., Meyne, J., Ratliff, R. L., & Wu, J. R. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.18.6622 · Cited by 2,326 · see citing works
Telomerase Catalytic Subunit Homologs from Fission Yeast and Human
Nakamura, T. M., Morin, G. B., Chapman, K. B., Weinrich, S. L., Andrews, W. H., Lingner, J., Harley, C. B., & Cech, T. R. (1997) · Science · doi:10.1126/science.277.5328.955 · Cited by 2,256 · see citing works
The RNA Component of Human Telomerase
Feng, J., Funk, W. D., Wang, S.-S., Weinrich, S. L., Avilion, A. A., Chiu, C.-P., Adams, R. R., Chang, E., Allsopp, R. C., Yu, J., et al. (1995) · Science · doi:10.1126/science.7544491 · Cited by 2,227 · see citing works
The delayed rise of present-day mammals
Bininda-Emonds, O. R. P., Cardillo, M., Jones, K. E., MacPhee, R. D. E., Beck, R. M. D., Grenyer, R., Price, S. A., Vos, R. A., Gittleman, J. L., & Purvis, A. (2007) · Nature · doi:10.1038/nature05634 · Cited by 2,082 · see citing works
Meyerson, M., Counter, C. M., Eaton, E. N., Ellisen, L. W., Steiner, P., Caddle, S. D., Ziaugra, L., Beijersbergen, R. L., Davidoff, M. J., Liu, Q., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)80538-3 · Cited by 1,784 · see citing works
A telomeric sequence in the RNA of Tetrahymena telomerase required for telomere repeat synthesis
Greider, C. W., & Blackburn, E. H. (1989) · Nature · doi:10.1038/337331a0 · Cited by 1,643 · see citing works
The Age Distribution of Cancer and a Multi-stage Theory of Carcinogenesis
Armitage, P., & Doll, R. (1954) · British Journal of Cancer · doi:10.1038/bjc.1954.1 · Cited by 1,549 · see citing works
Bayesian Estimation of Ancestral Character States on Phylogenies
Pagel, M. D., Meade, A., & Barker, D. (2004) · Systematic Biology · doi:10.1080/10635150490522232 · Cited by 1,381 · see citing works
Self-citationThe age distribution of cancer and a multi-stage theory of carcinogenesis
Armitage, P., & Doll, R. (2004) · British Journal of Cancer · doi:10.1038/sj.bjc.6602297 · Cited by 1,309 · 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
“This shortening is prevented in the germline and certain stem cells (Lee et al., 1998) by the presence of telomerase.”
BackgroundBody size, metabolic rate, generation time, and the molecular clock.
Martin, A. P., & Palumbi, S. R. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.9.4087 · Cited by 1,239 · cited 1× · see citing works
“…to the hypothesis that one of the early adaptations to becoming homeothermic, with its accompanying increased mutational load (Adelman et al., 1988; Martin & Palumbi, 1993; Rand, 1994), was the repression of telomerase in adult somatic cells, where the consequent progressive telomere shortening…”
BackgroundMammalian Telomeres Resemble Fragile Sites and Require TRF1 for Efficient Replication
Sfeir, A., Kosiyatrakul, S. T., Hockemeyer, D., MacRae, S. L., Karlseder, J., Schildkraut, C. L., & de Lange, T. (2009) · Cell · doi:10.1016/j.cell.2009.06.021 · Cited by 990 · see citing works
Makarov, V. L., Hirose, Y., & Langmore, J. P. (1997) · Cell · doi:10.1016/s0092-8674(00)81908-x · Cited by 923 · see citing works
Cheshier, S. H., Morrison, S. J., Liao, X., & Weissman, I. L. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.6.3120 · Cited by 858 · see citing works
Oxidative DNA damage through long-range electron transfer
Hall, D. B., Holmlin, R. E., & Barton, J. K. (1996) · Nature · doi:10.1038/382731a0 · Cited by 825 · see citing works
Sherr, C. J., & DePinho, R. A. (2000) · Cell · doi:10.1016/s0092-8674(00)00046-5 · Cited by 745 · see citing works
Senescence and immortalization: role of telomeres and telomerase
Shay, J. W., & Wright, W. E. (2004) · Carcinogenesis · doi:10.1093/carcin/bgh296 · Cited by 729 · see citing works
Self-citationTelomerase modulates Wnt signalling by association with target gene chromatin
Park, J.-I., Venteicher, A. S., Hong, J. Y., Choi, J., Jun, S., Shkreli, M., Chang, W., Meng, Z., Cheung, P., Ji, H., et al. (2009) · Nature · doi:10.1038/nature08137 · Cited by 707 · see citing works
Phylogenetic Analysis and Comparative Data: A Test and Review of Evidence
Freckleton, Harvey, & Pagel (2002) · The American Naturalist · doi:10.2307/3078855 · Cited by 631 · see citing works
Oxidative damage to DNA: relation to species metabolic rate and life span.
Adelman, R., Saul, R. L., & Ames, B. N. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.8.2706 · Cited by 580 · see citing works
Blackburn, E. H. (1992) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.61.070192.000553 · Cited by 543 · see citing works
Extension of Cell Life-Span and Telomere Length in Animals Cloned from Senescent Somatic Cells
Lanza, R. P., Cibelli, J. B., Blackwell, C., Cristofalo, V. J., Francis, M. K., Baerlocher, G. M., Mak, J., Schertzer, M., Chavez, E. A., Sawyer, N., et al. (2000) · Science · doi:10.1126/science.288.5466.665 · Cited by 466 · see citing works
Site‐specific DNA damage at GGG sequence by oxidative stress may accelerate telomere shortening
Oikawa, S., & Kawanishi, S. (1999) · FEBS Letters · doi:10.1016/s0014-5793(99)00748-6 · Cited by 435 · see citing works
Preferential Accumulation of Single-Stranded Regions in Telomeres of Human Fibroblasts
Petersen, S., Saretzki, G., & Zglinicki, T. V. (1998) · Experimental Cell Research · doi:10.1006/excr.1997.3893 · Cited by 427 · see citing works
Primitive Early Eocene bat from Wyoming and the evolution of flight and echolocation
Simmons, N. B., Seymour, K. L., Habersetzer, J., & Gunnell, G. F. (2008) · Nature · doi:10.1038/nature06549 · Cited by 403 · see citing works
Wright, W. E., & Shay, J. W. (2000) · Nature Medicine · doi:10.1038/78592 · Cited by 398 · see citing works
Self-citationMultistage carcinogenesis and the incidence of colorectal cancer
Luebeck, E. G., & Moolgavkar, S. H. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.222118199 · Cited by 360 · see citing works
Kapahi, P., Takahashi, T., Natoli, G., Adams, S., Chen, Y., Tsien, R. Y., & Karin, M. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m007204200 · Cited by 359 · see citing works
Current Protocols in Cell Biology
(2018) · Current Protocols in Cell Biology · doi:10.1002/(issn)1934-2616 · Cited by 359 · see citing works
Positive correlation between mammalian life span and cellular resistance to stress
Kapahi, P., Boulton, M. E., & Kirkwood, T. B. L. (1999) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(98)00323-2 · Cited by 326 · see citing works
Thermal habit, metabolic rate and the evolution of mitochondrial DNA
Rand, D. M. (1994) · Trends in Ecology & Evolution · doi:10.1016/0169-5347(94)90176-7 · Cited by 245 · see citing works
Telomerase activity coevolves with body mass not lifespan
Seluanov, A., Chen, Z., Hine, C., Sasahara, T. H. D. C., Ribeiro, A. A. C. M., Catania, K. C., Presgraves, D. C., & Gorbunova, V. A. (2006) · Aging Cell · doi:10.1111/j.1474-9726.2006.00262.x · Cited by 228 · see citing works
Gomes, N. M. V., Shay, J. W., & Wright, W. E. (2010) · FEBS Letters · doi:10.1016/j.febslet.2010.07.031 · Cited by 186 · see citing works
Self-citationLack of Replicative Senescence in Normal Rodent Glia
Mathon, N. F., Malcolm, D. S., Harrisingh, M. C., Cheng, L., & Lloyd, A. C. (2001) · Science · doi:10.1126/science.1056782 · Cited by 180 · see citing works
Harper, J. M., Salmon, A. B., Leiser, S. F., Gałecki, A. T., & Miller, R. A. (2006) · Aging Cell · doi:10.1111/j.1474-9726.2006.00255.x · Cited by 156 · see citing works
Human diseases of telomerase dysfunction: insights into tissue aging
Garcia, C. K., Wright, W. E., & Shay, J. W. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm644 · Cited by 156 · see citing works
Self-citationCoevolution of telomerase activity and body mass in mammals: From mice to beavers
Gorbunova, V. A., & Seluanov, A. (2008) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2008.02.008 · Cited by 138 · see citing works
Clues to catastrophic telomere loss in mammals from yeast telomere rapid deletion
Lustig, A. J. (2003) · Nature Reviews Genetics · doi:10.1038/nrg1207 · Cited by 136 · see citing works
Erratum: The delayed rise of present-day mammals
Bininda‐Emonds, O. R. P., Cardillo, M., Jones, K. E., MacPhee, R. D. E., Beck, R. M. D., Grenyer, R., Price, S. A., Vos, R. A., Gittleman, J. L., & Purvis, A. (2008) · Nature · doi:10.1038/nature07347 · Cited by 127 · see citing works
Immortalisation and transformation revisited
Drayton, S. (2002) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(01)00271-4 · Cited by 126 · see citing works
Yang, F., Graphodatsky, A. S., O'Brien, P. C. M., Colabella, A., Solanky, N., Squire, M., Sargan, D. R., & Ferguson-Smith, M. A. (2000) · Chromosome Research · doi:10.1023/a:1009210803123 · Cited by 112 · see citing works
Telomerase Activity Does Not Always Imply Telomere Maintenance
Ouellette, M. M., Aisner, D. L., Savre‐Train, I., Wright, W. E., & Shay, J. W. (1999) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.0114 · Cited by 106 · see citing works
Self-citationThe relative quiescence of hematopoietic stem cells in nonhuman primates
Mahmud, N., Devine, S. M., Weller, K. P., Parmar, S., Sturgeon, C., Nelson, M. C., Hewett, T. A., & Hoffman, R. (2001) · Blood · doi:10.1182/blood.v97.10.3061 · Cited by 101 · see citing works
Telomere Biology and Cellular Aging in Nonhuman Primate Cells
Steinert, S., White, D. M., Zou, Y. S., Shay, J. W., & Wright, W. E. (2002) · Experimental Cell Research · doi:10.1006/excr.2001.5409 · Cited by 99 · see citing works
Self-citationMontgomery, S. H., Capellini, I., Barton, R. A., & Mundy, N. I. (2010) · BMC Biology · doi:10.1186/1741-7007-8-9 · Cited by 98 · see citing works
Human Telomeres Maintain Their Overhang Length at Senescence
Chai, W., Shay, J. W., & Wright, W. E. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.6.2158-2168.2005 · Cited by 72 · see citing works
Self-citationGenotypic sex determination enabled adaptive radiations of extinct marine reptiles
Organ, C. L., Janes, D. E., Meade, A., & Pagel, M. D. (2009) · Nature · doi:10.1038/nature08350 · Cited by 71 · see citing works
Self-citationUpregulation of Telomerase Function During Tissue Regeneration
Elmore, L. W., Norris, M. W., Sircar, S., Bright, A. T., McChesney, P. A., Winn, R. N., & Holt, S. E. (2008) · Experimental Biology and Medicine · doi:10.3181/0712-rm-345 · Cited by 69 · see citing works
Analysis of Telomeres and Telomerase
Herbert, B., Shay, J. W., & Wright, W. E. (2003) · Current Protocols in Cell Biology · doi:10.1002/0471143030.cb1806s20 · Cited by 66 · see citing works
Self-citationHuman telomerase can immortalize Indian muntjac cells.
Zou, Y. S., Yi, X., Wright, W., & Shay, J. (2002) · Experimental Cell Research · doi:10.1006/excr.2002.5645 · Cited by 55 · see citing works
Oh, H.-Y., Jin, X., Kim, J. G., Oh, M., Pian, X., Kim, J., Yoon, M.-S., Son, C.-I., Lee, Y. S., Hong, K., et al. (2007) · BMC Cell Biology · doi:10.1186/1471-2121-8-20 · Cited by 51 · see citing works
Telomeres and telomerase activity in pig tissues
Fradiani, P. A., Ascenzioni, F., Lavitrano, M., & Donini, P. (2003) · Biochimie · doi:10.1016/j.biochi.2003.11.009 · Cited by 51 · see citing works
Cui, W., Aslam, S., Fletcher, J. M., Wylie, D., Clinton, M., & Clark, A. J. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m205981200 · Cited by 46 · see citing works
Lagomorphs (rabbits, pikas and hares) do not use telomere-directed replicative aging in vitro
Forsyth, N. R., Elder, F. F. B., Shay, J. W., & Wright, W. E. (2005) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2005.01.003 · Cited by 38 · see citing works
Self-citationFlamigni, F., Marmiroli, S., Caldarera, C. M., & Guarnieri, C. (1989) · Biochemical Journal · doi:10.1042/bj2590111 · Cited by 32 · see citing works
Wynshaw-Boris, A. J. (2007) · Nature · doi:10.1038/446274a · Cited by 5 · see citing works
Telomerase activity in human germline and embryonic tissues and cells
Wright, W. E., Piatyszek, M. A., Rainey, W. E., Byrd, W., & Shay, J. W. (1996) · Developmental Genetics · doi:10.1002/(sici)1520-6408(1996)18:2
Self-citation
Flagged first, then by citations
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Sorted by citations
Ageing as a Risk Factor for Disease
Niccoli, T., & Partridge, L. (2012) · Current Biology · doi:10.1016/j.cub.2012.07.024 · Cited by 1,831 · see citing works
Telomeres and telomerase: three decades of progress
Shay, J. W., & Wright, W. E. (2019) · Nature Reviews Genetics · doi:10.1038/s41576-019-0099-1 · Cited by 924 · see citing works
Self-citationTelomeric DNA damage is irreparable and causes persistent DNA-damage-response activation
Fumagalli, M., Rossiello, F., Clerici, M., Barozzi, S., Cittaro, D., Kaplunov, J. M., Bucci, G., Dobreva, M., Matti, V., Beausejour, C. M., et al. (2012) · Nature Cell Biology · doi:10.1038/ncb2466 · Cited by 851 · see citing works
Telomeres in cancer: tumour suppression and genome instability
Maciejowski, J., & de Lange, T. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.171 · Cited by 745 · see citing works
Telomere length in early life predicts lifespan
Heidinger, B. J., Blount, J. D., Boner, W., Griffiths, K., Metcalfe, N. B., & Monaghan, P. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1113306109 · Cited by 713 · see citing works
Role of Telomeres and Telomerase in Aging and Cancer
Shay, J. W. (2016) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-0062 · Cited by 668 · see citing works
Self-citationRole of telomeres and telomerase in cancer
Shay, J. W., & Wright, W. E. (2011) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2011.10.001 · Cited by 523 · see citing works
Self-citationYuan, X., Larsson, C., & Xu, D. (2019) · Oncogene · doi:10.1038/s41388-019-0872-9 · Cited by 450 · see citing works
Telomere shortening rate predicts species life span
Whittemore, K., Vera, E., Martínez-Nevado, E., Sanpera, C., & Blasco, M. A. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1902452116 · Cited by 373 · see citing works
Oxidative damage, ageing, and life-history evolution: where now?
Selman, C., Blount, J. D., Nussey, D. H., & Speakman, J. R. (2012) · Trends in Ecology & Evolution · doi:10.1016/j.tree.2012.06.006 · Cited by 385 · see citing works
How ageing processes influence cancer
de Magalhães, J. P. (2013) · Nature Reviews Cancer · doi:10.1038/nrc3497 · Cited by 367 · see citing works
Sex differences in telomeres and lifespan
Barrett, E. L. B., & Richardson, D. S. (2011) · Aging Cell · doi:10.1111/j.1474-9726.2011.00741.x · Cited by 366 · see citing works
Regulation of human telomerase in homeostasis and disease
Roake, C. M., & Artandi, S. E. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0234-z · Cited by 341 · see citing works
Stress, cell senescence and organismal ageing
de Magalhães, J. P., & Passos, J. F. (2018) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2017.07.001 · Cited by 316 · see citing works
Mechanisms of cancer resistance in long-lived mammals
Seluanov, A., Gladyshev, V. N., Vijg, J., & Gorbunova, V. A. (2018) · Nature reviews. Cancer · doi:10.1038/s41568-018-0004-9 · Cited by 330 · see citing works
Telomeres and Telomere Length: A General Overview
Srinivas, N., Rachakonda, P. S., & Kumar, R. (2020) · Cancers · doi:10.3390/cancers12030558 · Cited by 313 · see citing works
Comparison of telomere length measurement methods
Lai, T., Wright, W. E., & Shay, J. W. (2018) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2016.0451 · Cited by 288 · see citing works
Self-citationWilbourn, R. V., Moatt, J. P., Froy, H., Walling, C. A., Nussey, D. H., & Boonekamp, J. J. (2018) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2016.0447 · Cited by 264 · see citing works
Obesity May Accelerate the Aging Process
Salvestrini, V., Sell, C., & Lorenzini, A. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00266 · Cited by 260 · see citing works
Leukocyte Telomere Length in Newborns: Implications for the Role of Telomeres in Human Disease
Factor-Litvak, P. R., Susser, E., Kezios, K., McKeague, I. W., Kark, J. D., Hoffman, M., Kimura, M., Wapner, R. J., & Aviv, A. (2016) · PEDIATRICS · doi:10.1542/peds.2015-3927 · Cited by 246 · see citing works
Comparative genetics of longevity and cancer: insights from long-lived rodents
Gorbunova, V. A., Seluanov, A., Zhang, Z., Gladyshev, V. N., & Vijg, J. (2014) · Nature Reviews Genetics · doi:10.1038/nrg3728 · Cited by 234 · see citing works
Organismal stress, telomeres and life histories
Monaghan, P. (2013) · Journal of Experimental Biology · doi:10.1242/jeb.090043 · Cited by 233 · see citing works
Changes in Regenerative Capacity through Lifespan
Yun, M. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms161025392 · Cited by 216 · see citing works
Telomere Dynamics in Mice and Humans
Calado, R. T., & Dumitriu, B. (2013) · Seminars in Hematology · doi:10.1053/j.seminhematol.2013.03.030 · Cited by 214 · see citing works
The Rate of Increase of Short Telomeres Predicts Longevity in Mammals
Vera, E., de Jesus, B. B., Foronda, M., Flores, J. M., & Blasco, M. A. (2012) · Cell Reports · doi:10.1016/j.celrep.2012.08.023 · Cited by 220 · see citing works
Telomere length and dynamics predict mortality in a wild longitudinal study
Barrett, E. L. B., Burke, T. A., Hammers, M., Komdeur, J., & Richardson, D. S. (2012) · Molecular Ecology · doi:10.1111/mec.12110 · Cited by 217 · see citing works
Measuring telomere length and telomere dynamics in evolutionary biology and ecology
Nussey, D. H., Baird, D. M., Barrett, E. L. B., Boner, W., Fairlie, J., Gemmell, N. J., Hartmann, N., Horn, T., Haussmann, M. F., Olsson, M. M., et al. (2014) · Methods in Ecology and Evolution · doi:10.1111/2041-210x.12161 · Cited by 203 · see citing works
The role of telomeres in the mechanisms and evolution of life-history trade-offs and ageing
Young, A. J. (2018) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2016.0452 · Cited by 192 · see citing works
DiLoreto, R., & Murphy, C. T. (2015) · Molecular Biology of the Cell · doi:10.1091/mbc.e14-06-1084 · Cited by 184 · see citing works
TZAP: A telomere-associated protein involved in telomere length control
Li, J. S. Z., Fusté, J. M., Simavorian, T., Bartocci, C., Tsai, J., Karlseder, J., & Denchi, E. L. (2017) · Science · doi:10.1126/science.aah6752 · Cited by 177 · see citing works
Mice with hyper-long telomeres show less metabolic aging and longer lifespans
Muñoz-Lorente, M. A., Cano-Martin, A. C., & Blasco, M. A. (2019) · Nature Communications · doi:10.1038/s41467-019-12664-x · Cited by 168 · see citing works
Growing old, yet staying young: The role of telomeres in bats’ exceptional longevity
Foley, N. M., Hughes, G. M., Huang, Z., Clarke, M., Jebb, D., Whelan, C., PETIT, E. J., Touzalin, F., Farcy, O., Jones, G., et al. (2018) · Science Advances · doi:10.1126/sciadv.aao0926 · Cited by 174 · see citing works
Recurrent evolution of vertebrate transcription factors by transposase capture
Cosby, R. L., Judd, J., Zhang, R., Zhong, A., Garry, N., Pritham, E. J., & Feschotte, C. (2021) · Science · doi:10.1126/science.abc6405 · Cited by 168 · see citing works
Grandmothers and the evolution of human longevity: A review of findings and future directions
Hawkes, K., & Coxworth, J. E. (2013) · Evolutionary Anthropology Issues News and Reviews · doi:10.1002/evan.21382 · Cited by 169 · see citing works
A method for measuring the distribution of the shortest telomeres in cells and tissues
Lai, T., Zhang, N., Noh, J., Mender, I., Tedone, E., Huang, E. E., Wright, W. E., Danuser, G. M., & Shay, J. W. (2017) · Nature Communications · doi:10.1038/s41467-017-01291-z · Cited by 171 · see citing works
Self-citationHerborn, K. A., Heidinger, B. J., Boner, W., Noguera, J. C., Adam, A., Daunt, F., & Monaghan, P. (2014) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.2013.3151 · Cited by 161 · see citing works
Rossiello, F., Herbig, U., Longhese, M. P., Fumagalli, M., & di Fagagna, F. D. (2014) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2014.06.009 · Cited by 156 · see citing works
Heritability of telomere variation: it is all about the environment!
Dugdale, H. L., & Richardson, D. S. (2018) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2016.0450 · Cited by 156 · see citing works
Reflections on telomere dynamics and ageing-related diseases in humans
Aviv, A., & Shay, J. W. (2018) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2016.0436 · Cited by 153 · see citing works
Self-citationThe rate of telomere loss is related to maximum lifespan in birds
Tricola, G. M., Simons, M. J. P., Atema, E., Boughton, R. K., Brown, J. L., Dearborn, D. C., Divoky, G. J., Eimes, J. A., Huntington, C. E., Kitaysky, A. S., et al. (2018) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2016.0445 · Cited by 149 · see citing works
Mutations, Cancer and the Telomere Length Paradox
Aviv, A., Anderson, J. J., & Shay, J. W. (2017) · Trends in cancer · doi:10.1016/j.trecan.2017.02.005 · Cited by 150 · see citing works
Self-citationEarly life stress and telomere length: Investigating the connection and possible mechanisms
Shalev, I. (2012) · BioEssays · doi:10.1002/bies.201200084 · Cited by 147 · see citing works
Cumulative stress in research animals: Telomere attrition as a biomarker in a welfare context?
Melissa Bateson, B. (2015) · BioEssays · doi:10.1002/bies.201500127 · Cited by 137 · see citing works
Molecular Mechanisms Determining Lifespan in Short- and Long-Lived Species
Tian, X., Seluanov, A., & Gorbunova, V. A. (2017) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2017.07.004 · Cited by 127 · see citing works
Buffenstein, R., Amoroso, V. G., Andziak, B., Avdieiev, S. S., Azpurua, J., Barker, A. J., Bennett, N. C., Brieño‐Enríquez, M. A., Bronner, G. N., Coen, C. W., et al. (2021) · Biological reviews/Biological reviews of the Cambridge Philosophical Society · doi:10.1111/brv.12791 · Cited by 118 · see citing works
Cohen, R. A., Marsiske, M., & Smith, G. E. (2019) · Handbook of clinical neurology · doi:10.1016/b978-0-12-804766-8.00010-8 · Cited by 124 · see citing works
Shorter telomere length in Europeans than in Africans due to polygenetic adaptation
Hansen, M. E. B., Hunt, S. C., Stone, R. C., Horvath, K., Herbig, U., Ranciaro, A., Hirbo, J. B., Beggs, W. R., Reiner, A. P., Wilson, J. G., et al. (2016) · Human Molecular Genetics · doi:10.1093/hmg/ddw070 · Cited by 115 · see citing works
Evolution of telomere maintenance and tumour suppressor mechanisms across mammals
Tian, X., Doerig, K. R., Park, R., Qin, A. C. R., Hwang, C., Neary, A., Gilbert, M. B., Seluanov, A., & Gorbunova, V. A. (2018) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2016.0443 · Cited by 109 · see citing works
Questioning causal involvement of telomeres in aging
Simons, M. J. P. (2015) · Ageing Research Reviews · doi:10.1016/j.arr.2015.08.002 · Cited by 108 · see citing works
Aston, K. I., Hunt, S. C., Susser, E., Kimura, M., Factor-Litvak, P. R., Carrell, D. T., & Aviv, A. (2012) · Molecular Human Reproduction · doi:10.1093/molehr/gas028 · Cited by 108 · see citing works
Telomeres in aging and disease: lessons from zebrafish
Carneiro, M. C., de Castro, I. P., & Ferreira, M. G. (2016) · Disease Models & Mechanisms · doi:10.1242/dmm.025130 · Cited by 105 · see citing works
Treating Cancer by Targeting Telomeres and Telomerase
Ivancich, M., Schrank, Z., Wojdyla, L. M., Leviskas, B., Kuckovic, A., Sanjali, A., & Puri, N. (2017) · Antioxidants · doi:10.3390/antiox6010015 · Cited by 106 · see citing works
Eisenberg, D. T. A., & Kuzawa, C. W. (2018) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2016.0442 · Cited by 108 · see citing works
Telomeres shorten more slowly in slow-aging wild animals than in fast-aging ones
Dantzer, B., & Fletcher, Q. E. (2015) · Experimental Gerontology · doi:10.1016/j.exger.2015.08.012 · Cited by 102 · see citing works
The deteriorating soma and the indispensable germline: gamete senescence and offspring fitness
Monaghan, P., & Metcalfe, N. B. (2019) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.2019.2187 · Cited by 100 · see citing works
Sex Differences in Aging: Genomic Instability
Fischer, K. E., & Riddle, N. C. (2017) · The Journals of Gerontology Series A · doi:10.1093/gerona/glx105 · Cited by 97 · see citing works
Ectothermic telomeres: it's time they came in from the cold
Olsson, M. M., Wapstra, E., & Friesen, C. R. (2018) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2016.0449 · Cited by 94 · see citing works
Telomeres, aging, and cancer: the big picture
Lansdorp, P. M. (2022) · Blood · doi:10.1182/blood.2021014299 · Cited by 95 · see citing works
Ludlow, A. T., Ludlow, L. W., & Roth, S. M. (2013) · BioMed Research International · doi:10.1155/2013/601368 · Cited by 93 · see citing works
Alternative splicing regulation of telomerase: a new paradigm?
Wong, M. S., Wright, W. E., & Shay, J. W. (2014) · Trends in Genetics · doi:10.1016/j.tig.2014.07.006 · Cited by 92 · see citing works
Self-citationInflammation as A Precursor of Atherothrombosis, Diabetes and Early Vascular Aging
Barbu, E., Popescu, M.-R., Popescu, A.-C., & Balanescu, S. M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23020963 · Cited by 91 · see citing works
Telomere dynamic in humans and animals: Review and perspectives in environmental toxicology
Louzon, M., Cœurdassier, M., Gimbert, F., Pauget, B., & de Vaufleury, A. (2019) · Environment International · doi:10.1016/j.envint.2019.105025 · Cited by 89 · see citing works
Risk Factors for Development of Canine and Human Osteosarcoma: A Comparative Review
Makielski, K. M., Mills, L. J., Sarver, A. L., Henson, M. S., Spector, L. G., Naik, S., & Modiano, J. F. (2019) · Veterinary Sciences · doi:10.3390/vetsci6020048 · Cited by 94 · see citing works
Decline in telomere length with increasing age across nonhuman vertebrates: A meta‐analysis
Remot, F., Ronget, V., Froy, H., Rey, B., Gaillard, J., Nussey, D., & Lemaitre, J. (2021) · Molecular Ecology · doi:10.1111/mec.16145 · Cited by 67 · see citing works
Contributions of Nonhuman Primates to Research on Aging
Didier, E. S., MacLean, A. G., Mohan, M., Didier, P. J., Lackner, A. A., & Kuroda, M. J. (2016) · Veterinary Pathology · doi:10.1177/0300985815622974 · Cited by 85 · see citing works
DeGregori, J. V. (2012) · Oncogene · doi:10.1038/onc.2012.281 · Cited by 84 · see citing works
Robust measurement of telomere length in single cells
Wang, F., Pan, X., Kalmbach, K., Seth-Smith, M. L., Ye, X., Antumes, D. M. F., Yin, Y., Liu, L., Keefe, D. L., & Weissman, S. M. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1306639110 · Cited by 83 · see citing works
Lidzbarsky, G. A., Gutman, D., Shekhidem, H. A., Sharvit, L. E., & Atzmon, G. (2018) · Frontiers in Medicine · doi:10.3389/fmed.2018.00104 · Cited by 80 · see citing works
Telomere Length and the Cancer–Atherosclerosis Trade-Off
Stone, R. C., Horvath, K., Kark, J. D., Susser, E., Tishkoff, S. A., & Aviv, A. (2016) · PLoS Genetics · doi:10.1371/journal.pgen.1006144 · Cited by 82 · see citing works
A framework for how environment contributes to cancer risk
Hochberg, M., & Noble, R. (2017) · Ecology Letters · doi:10.1111/ele.12726 · Cited by 80 · see citing works
Cellular senescence and kidney aging
Rex, N., Melk, A., & Schmitt, R. (2023) · Clinical Science · doi:10.1042/cs20230140 · Cited by 83 · see citing works
Cell-Free Fetal DNA, Telomeres, and the Spontaneous Onset of Parturition
Phillippe, M. (2015) · Reproductive Sciences · doi:10.1177/1933719115592714 · Cited by 76 · see citing works
DNA damage tolerance in stem cells, ageing, mutagenesis, disease and cancer therapy
Pilzecker, B., Buoninfante, O. A., & Jacobs, H. (2019) · Nucleic Acids Research · doi:10.1093/nar/gkz531 · Cited by 71 · see citing works
Pharmaceutical regulation of telomerase and its clinical potential
Sprouse, A. A., Steding, C. E., & Herbert, B. (2011) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2011.01460.x · Cited by 69 · see citing works
Aviv, A., & Susser, E. (2013) · International Journal of Epidemiology · doi:10.1093/ije/dys236 · Cited by 70 · see citing works
Telomeres Shorten in Response to Oxidative Stress in Mouse Skeletal Muscle Fibers
Ludlow, A. T., Spangenburg, E. E., Chin, E. R., Cheng, W., & Roth, S. M. (2014) · The Journals of Gerontology Series A · doi:10.1093/gerona/glt211 · Cited by 71 · see citing works
Telomere Length Dynamics and the Evolution of Cancer Genome Architecture
Cleal, K., Norris, K., & Baird, D. M. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19020482 · Cited by 71 · see citing works
Telomerase activation: A potential key modulator for human healthspan and longevity
Boccardi, V., & Paolisso, G. (2014) · Ageing Research Reviews · doi:10.1016/j.arr.2013.12.006 · Cited by 69 · see citing works
Sławińska, N., & Krupa, R. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22020590 · Cited by 68 · see citing works
Varela, E., Muñoz-Lorente, M. A., Tejera, Á. M., Ortega, S., & Blasco, M. A. (2016) · Nature Communications · doi:10.1038/ncomms11739 · Cited by 67 · see citing works
All's well that ends well: why large species have short telomeres
Risques, R. A., & Promislow, D. (2018) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2016.0448 · Cited by 66 · see citing works
Kesäniemi, J., Lavrinienko, A., Tukalenko, E., Boratyński, Z., Kivisaari, K., Mappes, T., Milinevsky, G. P., Møller, A. P., Mousseau, T. A., & Watts, P. C. (2019) · Scientific Reports · doi:10.1038/s41598-018-37164-8 · Cited by 63 · see citing works
Telomeres and Longevity: A Cause or an Effect?
Shekhidem, H. A., Sharvit, L. E., Leman, E., Manov, I., Roichman, A., Holtze, S., Huffman, D. M., Cohen, H. Y., Hildebrandt, T. B., Shams, I., et al. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20133233 · Cited by 65 · see citing works
Telomerase as a Therapeutic Target in Cardiovascular Disease
Hoffmann, J., Richardson, G. D., Haendeler, J., Altschmied, J., Andrés, V., & Spyridopoulos, I. (2021) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.120.315695 · Cited by 65 · see citing works
Ageing as a software design flaw
de Magalhães, J. P. (2023) · Genome biology · doi:10.1186/s13059-023-02888-y · Cited by 66 · see citing works
Raj, D. D. A., Moser, J., van der Pol, S. M. A., van Os, R. P., Holtman, I. R., Brouwer, N., Oeseburg, H., Schaafsma, W., Wesseling, E. M., den Dunnen, W. F. A., et al. (2015) · Aging Cell · doi:10.1111/acel.12370 · Cited by 63 · see citing works
Chromosomal instability—mechanisms and consequences
Venkatesan, S., Natarajan, A. T., & Hande, M. P. (2015) · Mutation Research/Genetic Toxicology and Environmental Mutagenesis · doi:10.1016/j.mrgentox.2015.08.008 · Cited by 61 · see citing works
Telomeres, Atherosclerosis, and Human Longevity
Aviv, A., Kark, J. D., & Susser, E. (2015) · Epidemiology · doi:10.1097/ede.0000000000000280 · Cited by 61 · see citing works
Telomeres and Telomerase in the Control of Stem Cells
Lupatov, A. Y., & Yarygin, K. N. (2022) · Biomedicines · doi:10.3390/biomedicines10102335 · Cited by 61 · see citing works
Regulation of Telomerase Alternative Splicing: A Target for Chemotherapy
Wong, M. S., Chen, L., Foster, C., Kainthla, R., Shay, J. W., & Wright, W. E. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.03.011 · Cited by 59 · see citing works
Self-citationTelomeres in Plants and Humans: Not So Different, Not So Similar
Schrumpfová, P. P., Fojtová, M., & Fajkus, J. (2019) · Cells · doi:10.3390/cells8010058 · Cited by 57 · see citing works
Telomere length and cardiovascular disease risk
Zhan, Y., & Hägg, S. (2019) · Current Opinion in Cardiology · doi:10.1097/hco.0000000000000613 · Cited by 57 · see citing works
Telomeres, cellular senescence, and aging: past and future
Eppard, M., Passos, J. F., & Victorelli, S. G. (2023) · Biogerontology · doi:10.1007/s10522-023-10085-4 · Cited by 61 · see citing works
Increasing the accuracy and precision of relative telomere length estimates by RT qPCR
Eastwood, J. R., Mulder, G., Verhulst, S., & Peters, A. (2017) · Molecular Ecology Resources · doi:10.1111/1755-0998.12711 · Cited by 57 · see citing works
Random Forest classification based on star graph topological indices for antioxidant proteins
Fernández-Blanco, E., Aguiar‐Pulido, V., Munteanu, C. R., & Dorado, J. (2012) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2012.10.006 · Cited by 56 · see citing works
Exposure to oxychlordane is associated with shorter telomeres in arctic breeding kittiwakes
Blévin, P., Angelier, F., Tartu, S., Ruault, S., Paco Bustamante, A., Herzke, D., Moe, B., Bech, C., Gabrielsen, G. W., Bustnes, J. O., et al. (2016) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2016.04.096 · Cited by 56 · see citing works
van Lieshout, S. H. J., Sparks, A. M., Bretman, A. J., Newman, C., Buesching, C. D., Burke, T. A., Macdonald, D. W., & Dugdale, H. L. (2020) · Journal of Evolutionary Biology · doi:10.1111/jeb.13728 · Cited by 53 · 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
Bender, H. S., Murchison, E. P., Pickett, H. A., Deakin, J. E., Strong, M. A., Conlan, C., McMillan, D. A., Neumann, A. A., Greider, C. W., Hannon, G. J., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0046195 · Cited by 54 · see citing works
Drivers of longitudinal telomere dynamics in a long‐lived bat species, Myotis myotis
Foley, N. M., PETIT, E. J., Brazier, T., Finarelli, J. A., Hughes, G. M., Touzalin, F., Puechmaille, S. J., & Teeling, E. C. (2020) · Molecular Ecology · doi:10.1111/mec.15395 · Cited by 55 · see citing works
- Authors
- Gomes, N. M. V., Ryder, O. A., Houck, M. L., Charter, S. J., Walker, W., Forsyth, N. R., Austad, S. N., Venditti, C., Pagel, M., Shay, J. W., & Wright, W. E.
- Affiliations
- University of Lisbon (PT)
- The University of Texas Southwestern Medical Center (US)
- Keele University (GB)
- University of Hull (GB)
- Santa Fe Institute (US)
- Corresponding author
- Wright, Woodring E.
- ORCID
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2011-06
- Volume
- 10
- Issue
- 5
- Pages
- 761-768
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- PMC
- PMC3387546
- OpenAlex
- W1483456062
- Cited by
- 464
- References
- 63
- Citations by year
- 2026: 18 · 2025: 33 · 2024: 34 · 2023: 33 · 2022: 36 · 2021: 41 · 2020: 40 · 2019: 39 · 2018: 39 · 2017: 30 · 2016: 24 · 2015: 26 · 2014: 19 · 2013: 24 · 2012: 24
- FWCI
- 15.26
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Aging Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- CentAUR (University of Reading) (acceptedVersion)
- Funders
- W. M. Keck Foundation
- National Marine Sanctuary Foundation
- European Commission
- Engineering and Physical Sciences Research Council (EP/H028277/1)
- Natural Environment Research Council (NE/C51992X/1)
- National Institute on Aging (AG 01228, R01AG001228)
- National Cancer Institute (P50CA070907)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Keywords
- telomeres, telomerase, mammalian evolution, ancestral states, replicative senescence, lifespan, telomere length, homeothermy, mutational burden, body size, cancer, comparative biology, phylogenetic analysis
- MeSH terms
- Aging, Animals, Cell Division, Cell Line, Enzyme Repression, Fibroblasts, Genetic Vectors, Humans, Longevity, Mammals, Oxidation-Reduction, Phenotype, Phylogeny, Regression Analysis, Transfection, Telomere, Telomerase, Evolution, Molecular, Body Size, Cell Cycle Checkpoints, Telomere Shortening
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