Telomere is a structure of the repetitive DNA sequence TTAGGG and protein complex, found in vertebrates. This protein complex is known as the shelterin complex. It is localized at the end of each chromosome to protect them from deterioration or fusion with other chromosomes. Although as being part of a chromosome, the telomere is inherited from parents to their offspring, its mode of inheritance is a crucial part of the genetic transmission process. Theoretically, germ cells are thought to be immortal as they link generations, suggesting that telomere length is completely inherited. Furthermore, several studies reported that sperm telomere length gets elongated with age. This observation is consistent with other studies, which have reported that, with advancing paternal age at the time of conception, telomere length of the offspring gets increased. However, the mechanism by which telomere becomes longer is not fully understood. Moreover, it has been reported that there is a negative correlation between maternal age at conception and the offspring’s telomere length; whereas other studies reported that there is no correlation between those data. Herein, we review our current understanding of these topics and compare different aspects of the telomere length behavior in germ cells, germ cells mortality and, in accordance, the risks of aging on reproduction.
Cite this paper
Rakha, A. (2021). Telomere Length Inheritance throughout Generations: Role of Germ Cell Mortality. Open Access Library Journal, 8, e7798. doi: http://dx.doi.org/10.4236/oalib.1107798.
Lindsey, J., McGill, N.I., Linsey, L.A., Green, D.K. and Cooke H.J. (1991) In Vivo Loss of Telomeric Repeats with Age in Humans. Mutation Research/DNAging, 256, 45-48. https://doi.org/10.1016/0921-8734(91)90032-7
Mather, K.A., Jorm, A.F., Parslow, R.A. and Christensen, H. (2010) Is Telomere Length a Biomarker of Aging? A Review. The Journals of Gerontology: Series A, 66A, 202-213.
Wright, W.E., Piatyszek, M.A., Rainey, W.E., Byrd, W. and Shay, J.W. (1996) Telomerase Activity in Human Germline and Embryonic Tissues and Cells. Developmental Genetics, 18, 173-179.
https://doi.org/10.1002/(SICI)1520-6408(1996)18:2%3C173::AID-DVG10%3E3.0.CO;2-3
Rakha, A. (2015) Cloning Efficiency and a Comparison between Donor Cell Types. Cloning and Transgenesis, 4, Article No. 141.
https://doi.org/10.4172/2168-9849.1000141
Huda, N., Tanaka, H., Herbert, B.S., Reed, T. and Gilley, D. (2007) Shared Environmental Factors Associated with Telomere Length Maintenance in Elderly Male Twins. Aging Cell, 6, 709-713. https://doi.org/10.1111/j.1474-9726.2007.00330.x
Epel, E.S., Blackburn, E.H., Lin, J., Dhabhar, F.S., Adler, N.E., Morrow, J.D. and Caw- thon, R.M. (2004) Accelerated Telomere Shortening in Response to Life Stress. Proceedings of the National Academy of Sciences of the United States of America, 101, 17312-17315. https://doi.org/10.1073/pnas.0407162101
Valdes, A.M., Andrew, T., Gardner, J.P., Kimura, M., Oelsner, E., Cherkas, L.F., Aviv, A. and Spector, T.D. (2005) Obesity, Cigarette Smoking, and Telomere Length in Wo- men. Lancet, 366, 662-664. https://doi.org/10.1016/S0140-6736(05)66630-5
Cherkas, L.F., Aviv, A., Valdes, A.M., Hunkin, J.L., Gardner, J.P., Surdulescu, G.L., Kimura, M. and Spector, T.D. (2006) The Effects of Social Status on Biological Aging as Measured by White-Blood-Cell Telomere Length. Aging Cell, 5, 361-365.
https://doi.org/10.1111/j.1474-9726.2006.00222.x
Shlush, L.I., Skoreckia, K.L., Itzkovitzc, S., Yehezkela, S., Segeva, Y., Shacharb, H., Berkovitzb, R., Adirb, Y., Vultod, I., Lansdorpd, P.M. and Seliga, S. (2011) Telomere Elongation Followed by Telomere Length Reduction, in Leukocytes from Divers Exposed to Intense Oxidative Stress—Implications for Tissue and Organismal Aging. Mechanisms of Ageing and Development, 132, 123-130.
https://doi.org/10.1016/j.mad.2011.01.005
Kadota, K., Hayakawa, K., Doi, S., Kanamori, M. and Cai, Y. (2007) Factors Affecting the Intrapair Differences of Telomere Length in Aged Identical Twins. Twin Research and Human Genetics, 10, Article No. 36.
Achi, M.V., Ravindranath, N. and Dym, M. (2000) Telomere Length in Male Germ Cells Is Inversely Correlated with Telomerase Activity. Biology of Reproduction, 63, 591-598. https://doi.org/10.1095/biolreprod63.2.591
Aston, K.I., Hunt, S.C., Susser, E., Kimura, M., Factor-Litvak, P., Carrell, D. and Aviv, A. (2012) Divergence of Sperm and Leukocyte Age-Dependent Telomere Dynamics: Implications for Male-Driven Evolution of Telomere Length in Humans. Molecular Human Reproduction, 18, 517-522. https://doi.org/10.1093/molehr/gas028
Unryn, B.M., Cook, L.S. and Riabowol, K.T. (2005) Paternal Age Is Positively Linked to Telomere Length of Children. Aging Cell, 4, 97-101.
https://doi.org/10.1111/j.1474-9728.2005.00144.x
De Meyer, T., Rietzschel, E.R., Buyzere, M.L.D., Bacquer, D.D., Criekinge, W.V., Backer, G.G.D., Gillebert, T.C., Oostveldt, P.V. and Bekaert, S. (2007) Paternal Age at Birth Is an Important Determinant of Offspring Telomere Length. Human Molecular Ge- neics, 16, 3097-3102. https://doi.org/10.1093/hmg/ddm271
Eisenberg, D.T.A., Borja, J.B., Hayes, M.G. and Kuzawa, C.W. (2017) Early Life Infection, but Not Breastfeeding, Predicts Adult Blood Telomere Lengths in the Philippines. American Journal of Human Biology, 29, e22962.
https://doi.org/10.1002/ajhb.22962
Ferlin, A., Rampazzo, E., Rocca, M.S., Keppel, S., Frigo, A.S., Rossi, A.D. and Foresta, C. (2013) In Young Men Sperm Telomere Length Is Related to Sperm Number and Parental Age. Human Reproduction, 28, 3370-3376.
https://doi.org/10.1093/humrep/det392
Broer, L., Codd, V., Nyholt, D.R., Deelen, J., Mangino, M., Willemsen, G., Albrecht, E., Amin, N., Beekman, M., Geus, E.J.D Henders, A., Nelson, C.P., Steves, C.J., Wright, M.J., de Craen, A.J.M., Isaacs, A., Matthews, M., Moayyeri, A., Montgomery, G.W., Oostra, B.A., Vink, J.M., Spector, T.D., Slagboom, P.E., Martin, N.G., Samani, N.J., van Duijn, C.M. and Boomsma, D.I. (2013) Meta-Analysis of Telomere Length in 19,713 Subjects Reveals High Heritability, Stronger Maternal Inheritance and a Paternal Age Effect. European Journal of Human Genetics, 21, 1163-1168.
https://doi.org/10.1038/ejhg.2012.303
Hjelmborg, A.B., Dalga, C., Mangino, M., Spector, T.D., Halekoh, U., Moller, S., Kimura, M., Horvath, K., Kark, J.D., Christensen, K., Kyvik, K.O. and Aviv, A. (2015) Paternal Age and Telomere Length in Twins: The Germ Stem Cell Selection Paradigm. Aging Cell, 14, 701-703. https://doi.org/10.1111/acel.12334
Okuda, K., Bardeguez, A., Gardner, J.P., Rodriguez, P., Ganesh, V., Kimura, M., Skur- nick, J., Awad, G. and Aviv, A. (2002) Telomere Length in the Newborn. Pediatric Pulmonology, 52, 377-381. https://doi.org/10.1203/00006450-200209000-00012
Keefe, D.L., Liu, L. and Marquard, K. (2007) Telomeres and Meiosis in Health and Disease: Telomeres and Aging-Related Meiotic Dysfunction in Women. Cellular and Molecular Life Sciences, 64, 139-143. https://doi.org/10.1007/s00018-006-6466-z
Eisenberg, D.T.A. and Kuzawa, C.W. (2018) The Paternal Age at Conception Effect on Offspring Telomere Length: Mechanistic, Comparative and Adaptive Perspectives. Philosophical Transactions of the Royal Society B, 373, Article ID: 20160442.
https://doi.org/10.1098/rstb.2016.0442
Arbeev, K.G., Hunt, S.C., Kimura, M., Aviv, A. and Yashin, A.I. (2011) Leukocyte Telomere Length, Breast Cancer Risk in the Offspring: The Relations with Father’s Age at Birth. Mechanisms of Ageing and Development, 132, 149-153.
https://doi.org/10.1016/j.mad.2011.02.004
Eisenberg, D.T.A., Hayesa, M.G. and Kuzawaa, C.W. (2012) Delayed Paternal Age of Reproduction in Humans Is Associated with Longer Telomeres across Two Generations of Descendants. Proceedings of the National Academy of Sciences of the United States of America, 109, 10251-10256.
https://doi.org/10.1073/pnas.1202092109
Crittenden, S.L., Troemel, E.R., Evans, T.C. and Kimble, J. (1994) GLP-1 Is Localized to the Mitotic Region of the C. elegans Germ Line. Development, 120, 2901-2911.
https://doi.org/10.1242/dev.120.10.2901
Pech, M.F., Garbuzov, A., Hasegawa, K., Sukhwani, M., Zhang, R.J., Benayoun, B.A., Brockman, S.A., Lin, S., Brunet, A., Orwig, K.E. and Artandi, S.E. (2015) High Telomerase Is a Hallmark of Undifferentiated Spermatogonia and Is Required for Maintenance of Male Germline Stem Cells. Genes & Development, 29, 2420-2434.
https://doi.org/10.1101/gad.271783.115
Antunes, D. F., Kalmbach, K., Wang, F., Dracxler, R., Seth-Smith, M., Kramer, Y., Buldo-Licciardi, J., Kohlrausch, F. and Keefe, D. (2015) A Single-Cell Assay for Telomere DNA Content Shows Increasing Telomere Length Heterogeneity, as Well as Increasing Mean Telomere Length in Human Spermatozoa with Advancing Age. Journal of Assisted Reproduction and Genetics, 32, 1685-1690.
https://doi.org/10.1007/s10815-015-0574-3
Goriely, A., McGrath, J.J., Wilkie, A.O.M. and Malaspina, D. (2013) “Selfish Spermato- gonial Selection”: A Novel Mechanism for the Association between Advanced Paternal Age and Neurodevelopmental Disorders. American Journal of Psychiatry, 170, 599-608. https://doi.org/10.1176/appi.ajp.2013.12101352
Maher, G.J., Goriely, A. and Wilkie, A.O. (2013) Cellular Evidence for Selfish Spermato- gonial Selection in Aged Human Testes. Andrology, 2, 304-314.
https://doi.org/10.1111/j.2047-2927.2013.00175.x
Goriely, A. and Wilkie, A.O.M. (2012) Paternal Age Effect Mutations and Selfish Sper- matogonial Selection: Causes and Consequences for Human Disease. American Journal of Human Genetics, 90, 175-200. https://doi.org/10.1016/j.ajhg.2011.12.017
Arnheim, N. and Calabrese, P. (2016) Germline Stem Cell Competition, Mutation Hot Spots, Genetic Disorders, and Older Fathers. Annual Review of Genomics and Human Genetics, 17, 219-243.
https://doi.org/10.1146/annurev-genom-083115-022656
Flores, I., Canela, A., Vera, E., Tejera, A., Cotsarelis, G. and Blasco, M.A. (2008) The Longest Telomeres: A General Signature of Adult Stem Cell Compartments. Genes & Development, 22, 654-667. https://doi.org/10.1101/gad.451008
Seluanov, A., Chen, Z., Hine, C., Sasahara, T., Ribeiro, A., Catania, K., Presgraves, D. and Gorbunova, V. (2007) Telomerase Activity Coevolves with Body Mass Not Lifespan. Aging Cell, 6, 45-52. https://doi.org/10.1111/j.1474-9726.2006.00262.x
Kim, N.M., Piatyszek, M.A., Prowse, K.R., Harley, C.B., West, M.D., Ho, P.L.C., Coviello, G.M., Wright, W.E., Weinrich, S.L. and Shay, J.W. (1994) Specific Association of Human Telomerase Activity with Immortal Cells and Cancer. Science, 266, 2011-2015. https://doi.org/10.1126/science.7605428
Yashima, K., Maitra, A., Rogers, B.B., Timmons, C.F., Rathi, A., Pinar, H., Wright, W.E., Shay, J.W. and Gazdar, A.F. (1998) Expression of the RNA Component of Telomerase during Human Development and Differentiation. Cell Growth & Differentiation, 9, 805-813.
Jorgensen, P.B., Fedder, J., Koelvraa, S. and Graakjaer, J. (2013) Age-Dependence of Relative Telomere Length Profiles during Spermatogenesis in Man. Maturitas, 75, 380-385. https://doi.org/10.1016/j.maturitas.2013.05.001
Erdem, H.B., Bahsi, T. and Ergün, M.A. (2021) Function of Telomere in Aging and Age Related Diseases. Environmental Toxicology and Pharmacology, 85, Article ID: 103641. https://doi.org/10.1016/j.etap.2021.103641
Egger, G., Liang, G., Aparicio, A. and Jones and P.A. (2004) Epigenetics in Human Disease and Prospects for Epigenetic Therapy. Nature, 429, 457-463.
https://doi.org/10.1038/nature02625
Asghar, M., Bensch, S., Tarka, M., Hansson, B. and Hasselquist D. (2015) Maternal and Genetic Factors Determine Early Life Telomere Length. Proceedings of the Royal Society B, 282, Article ID: 20142263. https://doi.org/10.1098/rspb.2014.2263
Kin, A., Kansaku, K., Sumiya, M., Itami, N., Sirasuna, K., Kuwayama, T. and Iwata, H. (2017) Effect of Aging on Telomere Lengths in Bovine Oocytes and Granulosa Cells. Journal of Mammalian Ova Research, 34, 37-43.
Gomes, N.M., Ryder, O.A., Houck, M.L., Charter, S.J., Walker, W., Forsyth, N.R., Austad, S.N., Venditti, C., Pagel, M., Shay, J.W. and Wright, W.E. (2011) Comparative Biology of Mammalian Telomeres: Hypotheses on Ancestral States and the Roles of Telomeres in Longevity Determination. Aging Cell, 10, 761-768.
https://doi.org/10.1111/j.1474-9726.2011.00718.x
Ozturk, S., Sozen, B. and Demir, N. (2013) Telomere Length and Telomerase Activity during Oocyte Maturation and Early Embryo Development in Mammalian Species. Molecular Human Reproduction, 20, 15-30.
https://doi.org/10.1093/molehr/gat055
Reizel, Y., Itzkovitz, S., Adar, R., Elbaz, J., Jinich, A., Chapal-Ilani, N., Maruvka, Y.E., Nevo, N., Marx, Z., Horovitz, I., Wasserstrom, A., Mayo, A., Shur, I., Benayahu, D., Skorecki, K., Segal, E., Dekel, N. and Shapiro, E. (2012) Cell Lineage Analysis of the Mammalian Female Germline. PLoS Genetics, 8, e1002477.
https://doi.org/10.1371/journal.pgen.1002477
Fromer, M., Pocklington, A.J., Kavanagh, D.H., Williams, H.J., Dwyer, S., Gormley, P., Georgieva, L., Rees, E., Palta, P., Ruderfer, D.M., Carrera, N., Humphreys, I., Johnson, J.S., Roussos, P., Barker, D.D., Banks, E., Milanova, V., Grant, S.G., Hannon, E., Rose, S.A., Chambert, K., Mahajan, M., Scolnick, E. M., Moran, J.L., Kirov, G., Palotie, A., McCarroll, S.A., Holmans, P., Sklar, P., Owen, M.J., Purcell, S. M. and O’Donovan, M.C. (2014) De Novo Mutations in Schizophrenia Implicate Synaptic Networks. Nature, 506, 179-184. https://doi.org/10.1038/nature12929
Krupp, G., Bonatz, G. and Parwaresch, R. (2000) Telomerase, Immortality and Cancer. Biotechnology Annual Review, 6, 103-140.
https://doi.org/10.1016/S1387-2656(00)06020-8
Turner, S. and Hartshorne, G.M. (2013) Telomere Lengths in Human Pronuclei, Oocytes and Spermatozoa. Molecular Human Reproduction, 19, 510-518.
https://doi.org/10.1093/molehr/gat021
Varela, E., Munoz-Lorente, M.A., Tejera, A.M., Ortega, S. and Blasco, M.A. (2016) Generation of Mice with Longer and Better Preserved Telomeres in the Absence of Genetic Manipulations. Nature Communications, 7, Article No. 11739.
https://doi.org/10.1038/ncomms11739
Aviv, A., Anderson, J.J. and Shay, J.W. (2017) Mutations, Cancer and the Telomere Length Paradox. Trends in Cancer, 3, 253-258.
https://doi.org/10.1016/j.trecan.2017.02.005
Sharma, R., Agarwal, A., Rohra, V.K., Assidi, M., Abu-Elmagd, M. and Turki, R.F. (2015) Effects of Increased Paternal Age on Sperm Quality, Reproductive Outcome and Associated Epigenetic Risks to Offspring. Reproductive Biology and Endocrinology, 13, Article No. 35. https://doi.org/10.1186/s12958-015-0028-x
Stone, B.A., Alex, A., Werlin, L.B. and Marrs, R.P. (2013) Age Thresholds for Changes in Semen Parameters in Men. Fertility and Sterility, 100, 952-958.
https://doi.org/10.1016/j.fertnstert.2013.05.046
Ehrlenbach, S., Willeit, P., Kiechl, S., Willeit, J., Reindl, M., Schanda, K., Kronenberg, F. and Brandstätter, A. (2009) Influences on the Reduction of Relative Telomere Length over 10 Years in the Population-Based Bruneck Study: Introduction of a Well- Controlled High-Throughput Assay. International Journal of Epidemiology, 38, 1725-1734. https://doi.org/10.1093/ije/dyp273
Fitzpatrick, A.L., Kronmal, R.A., Kimura, M., Gardner, J.P., Psaty, B.M., Jenny, N.S., Tracy, R.P., Hardikar, S. and Aviv, A. (2011) Leukocyte Telomere Length and Mortality in the Cardiovascular Health Study. Journal of Gerontology and Geriatrics: Series A, 66, 421-429. https://doi.org/10.1093/gerona/glq224
Aydos, S.E., Elhan, A.H. and Tükün, A. (2005) Is Telomere Length One of the Determinants of Productive Life Span? Archives of Gynecology and Obstetrics, 272, 113-116.
https://doi.org/10.1007/s00404-004-0690-2
Gray, K.E., Schiff, M.A., Fitzpatrick, A.L., Kimura, M., Aviv, A. and Starr, J.R. (2014) Leukocyte Telomere Length and Age at Menopause. Epidemiology, 25, 139-146.
https://doi.org/10.1097/EDE.0000000000000017
Shenassa, E.D. and Rossen, L.M. (2015) Telomere Length and Age-at-Menopause in the US. Maturitas, 82, 215-221. https://doi.org/10.1016/j.maturitas.2015.07.009
Haycock, P.C., Burgess, S., Nounu, A., Zheng, J., Okoli, G.N., et al. (2017) Association between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases: A Men- delian Randomization Study. JAMA Oncology, 3, 636-651.
https://doi.org/10.1001/jamaoncol.2016.5945
Zhu, X., Han, W., Xue, W., Zou, Y., Xie, C., Du, J. and Jin, G. (2016) The Association between Telomere Length and Cancer Risk in Population Studies. Scientific Reports, 6, Article No. 22243. https://doi.org/10.1038/srep22243
Rode, L., Nordestgaard, B.G. and Bojesen, S.E. (2016) Long Telomeres and Cancer Risk among 95,568 Individuals from the General Population. International Journal of Epidemiology, 45, 1634-1643. https://doi.org/10.1093/ije/dyw179