Comparative biology of mammalian telomeres: hypotheses on ancestral states and the roles of telomeres in longevity determination.
Comparative biology of mammalian telomeres: hypotheses on ancestral states and the roles of telomeres in longevity determination.
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DOI：
10.1111/j.1474-9726.2011.00718.x
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发表时间：
2011-10
期刊：
影响因子：
7.8
通讯作者：
Wright WE
中科院分区：
文献类型：
--
作者：
Gomes NM;Ryder OA;Houck ML;Charter SJ;Walker W;Forsyth NR;Austad SN;Venditti C;Pagel M;Shay JW;Wright WE
细胞分裂导致的端粒进行性缩短（复制性衰老）为人类肿瘤进展提供了障碍。该程序在实验室小鼠中不保守，其具有较长的端粒和组成型端粒酶。已经报道了野生物种不使用复制老化，但缺乏不同表型的进化和理解其端粒用途的概念框架。我们检查了来自> 60种哺乳动物的培养细胞中的端粒/端粒酶，以在广泛的哺乳动物背景下放置端粒的不同用途。基于系统发育的统计分析重建了祖先国家。我们的分析表明，祖先哺乳动物的表型包括短端粒（< 20 kb，正如我们现在在人类中看到的那样）和受抑制的端粒酶。我们认为，被抑制的端粒酶是对恒温进化带来的更高突变负荷的反应。随着端粒酶的抑制，我们看到了复制性衰老的进化。端粒长度与寿命呈负相关，而端粒酶表达与体型共同进化。多个独立的倍更小，寿命更短的物种改变为具有更长的端粒和表达端粒酶。涉及减少特定氧化保护机制（在没有端粒酶的情况下保护< 20 kb端粒所需）的能量/细胞成本的权衡可以解释这种放弃复制性衰老的原因。这些观察结果为理解端粒在哺乳动物中的不同用途提供了概念框架，支持了类人端粒在允许更长寿命进化中的作用，证明了在分析衰老生物学中氧化保护的比较研究时需要包括端粒长度，并确定哪些哺乳动物可用作研究端粒在人类癌症和衰老中作用的适当模式生物。
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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影响因子：
3.2
作者：
Elmore, Lynne W.;Norris, Michelle W.;Holt, Shawn E.
通讯作者：
Holt, Shawn E.
DOI：
10.1073/pnas.222118199
发表时间：
2002-11-12
影响因子：
11.1
作者：
Luebeck, EG;Moolgavkar, SH
通讯作者：
Moolgavkar, SH
影响因子：
5.3
作者：
Chai, WH;Shay, JW;Wright, WE
通讯作者：
Wright, WE
影响因子：
56.9
作者：
FENG, JL;FUNK, WD;VILLEPONTEAU, B
通讯作者：
VILLEPONTEAU, B
影响因子：
14.9
作者：
Garcia, Christine Kim;Wright, Woodring E;Shay, Jerry W
通讯作者：
Shay, Jerry W