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      Distinct telomere differences within a reproductively bimodal common lizard population

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          Abstract

          1. Different strategies of reproductive mode, either oviparity (egg‐laying) or viviparity (live‐bearing), will be associated with a range of other life‐history differences that are expected to affect patterns of ageing and longevity. It is usually difficult to compare the effects of alternative reproductive modes because of evolutionary and ecological divergence. However, the very rare exemplars of reproductive bimodality, in which different modes exist within a single species, offer an opportunity for robust and controlled comparisons.

          2. One trait of interest that could be associated with life history, ageing and longevity is the length of the telomeres, which form protective caps at the chromosome ends and are generally considered a good indicator of cellular health. The shortening of these telomeres has been linked to stressful conditions; therefore, it is possible that differing reproductive costs will influence patterns of telomere loss. This is important because a number of studies have linked a shorter telomere length to reduced survival.

          3. Here, we have studied maternal and offspring telomere dynamics in the common lizard ( Zootoca vivipara). Our study has focused on a population where oviparous and viviparous individuals co‐occur in the same habitat and occasionally interbreed to form admixed individuals.

          4. While viviparity confers many advantages for offspring, it might also incur substantial costs for the mother, for example require more energy. Therefore, we predicted that viviparous mothers would have relatively shorter telomeres than oviparous mothers, with admixed mothers having intermediate telomere lengths. There is thought to be a heritable component to telomere length; therefore, we also hypothesized that offspring would follow the same pattern as the mothers.

          5. Contrary to our predictions, the viviparous mothers and offspring had the longest telomeres, and the oviparous mothers and offspring had the shortest telomeres. The differing telomere lengths may have evolved as an effect of the life‐history divergence between the reproductive modes, for example due to the increased growth rate that viviparous individuals may undergo to reach a similar size at reproduction.

          A free http://onlinelibrary.wiley.com/doi/10.1111/1365-2435.13408/suppinfo can be found within the Supporting Information of this article.

          Abstract

          A free http://onlinelibrary.wiley.com/doi/10.1111/1365-2435.13408/suppinfo can be found within the Supporting Information of this article.

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          Telomere end-replication problem and cell aging.

          Since DNA polymerase requires a labile primer to initiate unidirectional 5'-3' synthesis, some bases at the 3' end of each template strand are not copied unless special mechanisms bypass this "end-replication" problem. Immortal eukaryotic cells, including transformed human cells, apparently use telomerase, an enzyme that elongates telomeres, to overcome incomplete end-replication. However, telomerase has not been detected in normal somatic cells, and these cells lose telomeres with age. Therefore, to better understand the consequences of incomplete replication, we modeled this process for a population of dividing cells. The analysis suggests four things. First, if single-stranded overhangs generated by incomplete replication are not degraded, then mean telomere length decreases by 0.25 of a deletion event per generation. If overhangs are degraded, the rate doubles. Data showing a decrease of about 50 base-pairs per generation in fibroblasts suggest that a full deletion event is 100 to 200 base-pairs. Second, if cells senesce after 80 doublings in vitro, mean telomere length decreases about 4000 base-pairs, but one or more telomeres in each cell will lose significantly more telomeric DNA. A checkpoint for regulation of cell growth may be signalled at that point. Third, variation in telomere length predicted by the model is consistent with the abrupt decline in dividing cells at senescence. Finally, variation in length of terminal restriction fragments is not fully explained by incomplete replication, suggesting significant interchromosomal variation in the length of telomeric or subtelomeric repeats. This analysis, together with assumptions allowing dominance of telomerase inactivation, suggests that telomere loss could explain cell cycle exit in human fibroblasts.
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            Comparative biology of mammalian telomeres: hypotheses on ancestral states and the roles of telomeres in longevity determination.

            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. © 2011 The Authors. Aging Cell © 2011 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.
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              The impact of oxidative DNA damage and stress on telomere homeostasis

              Telomeres are dynamic nucleoprotein-DNA structures that cap and protect linear chromosome ends. Because telomeres shorten progressively with each replication, they impose a functional limit on the number of times a cell can divide. Critically short telomeres trigger cellular senescence in normal cells, or genomic instability in pre-malignant cells, which contribute to numerous degenerative and aging-related diseases including cancer. Therefore, a detailed understanding of the mechanisms of telomere loss and preservation is important for human health. Numerous studies have shown that oxidative stress is associated with accelerated telomere shortening and dysfunction. Oxidative stress caused by inflammation, intrinsic cell factors or environmental exposures, contributes to the pathogenesis of many degenerative diseases and cancer. Here we review the studies demonstrating associations between oxidative stress and accelerated telomere attrition in human tissue, mice and cell culture, and discuss possible mechanisms and cellular pathways that protect telomeres from oxidative damage.
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                Author and article information

                Contributors
                darrylmclennan@outlook.com
                Journal
                Funct Ecol
                Funct Ecol
                10.1111/(ISSN)1365-2435
                FEC
                Functional Ecology
                John Wiley and Sons Inc. (Hoboken )
                0269-8463
                1365-2435
                30 July 2019
                October 2019
                : 33
                : 10 ( doiID: 10.1111/fec.v33.10 )
                : 1917-1927
                Affiliations
                [ 1 ] Institute of Biodiversity, Animal Health and Comparative Medicine University of Glasgow Glasgow UK
                [ 2 ] Department of Fish Ecology and Evolution EAWAG Kastanienbaum Switzerland
                Author notes
                [*] [* ] Correspondence

                Darryl McLennan

                Email: darrylmclennan@ 123456outlook.com

                Author information
                https://orcid.org/0000-0002-8566-9437
                https://orcid.org/0000-0003-2728-0690
                https://orcid.org/0000-0002-9219-7001
                Article
                FEC13408
                10.1111/1365-2435.13408
                6853248
                31762528
                dc862055-98e7-4172-84f0-bf693d798233
                © 2019 The Authors. Functional Ecology published by John Wiley & Sons Ltd on behalf of British Ecological Society

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 13 April 2019
                : 18 June 2019
                : 03 July 2019
                Page count
                Figures: 3, Tables: 3, Pages: 11, Words: 9057
                Funding
                Funded by: Natural Environment Research Council , open-funder-registry 10.13039/501100000270;
                Award ID: NE/N003942/1
                Funded by: H2020 European Research Council , open-funder-registry 10.13039/100010663;
                Award ID: 322784
                Categories
                Research Article
                Animal Physiological Ecology
                Custom metadata
                2.0
                October 2019
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.7.1 mode:remove_FC converted:13.11.2019

                Ecology
                life‐history variation,oviparity,physiological state,squamate,viviparity
                Ecology
                life‐history variation, oviparity, physiological state, squamate, viviparity

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