The evolutionary biology of telomeres

端粒的进化生物学

基本信息

  • 批准号:
    1519110
  • 负责人:
  • 金额:
    $ 35.27万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
    Continuing Grant
  • 财政年份:
    2015
  • 资助国家:
    美国
  • 起止时间:
    2015-07-15 至 2018-06-30
  • 项目状态:
    已结题

项目摘要

In the U.S. and many other countries people are increasingly putting off starting families until later in life. Correspondingly there is growing concern about the effects of mothers' and fathers' ages on the biology of their offspring. This research examines an important genetic marker of aging, telomere length, that is thought to be influenced by paternal age. Telomeres are DNA that cap the ends of chromosomes, and that shorten with cell replication, oxidative stress, and age. Contrary to other findings, older paternal age might have positive influences on telomere length that promote offspring longevity. This proposal will collect family tree histories and measure telomere lengths in order to better discern whether paternal age actually influences telomere length, and whether this effect persists across generations (e.g. whether grandfather's age or great-grandfather's age at reproduction influences descendants' telomere lengths). Additionally this proposal will examine whether telomere length influences early life immune function in addition to aging. These investigations will therefore contribute to the larger understanding of the evolution of human life history. Broader impacts include the production of a valuable shared dataset that will be relevant to human biologists and public health researchers, and integration of the project analysis and data into student training, mentoring and curricula. Models for the evolution of senescence assume that when individuals reproduce at advanced ages, selection will favor increased maintenance effort and a corresponding slowing of senescence. Inter-specific comparisons and selection experiments in model organisms have demonstrated that lower mortality/later ages of reproduction are associated with lifespan extension, broadly supporting these theoretical expectations. While natural selection operating on gene frequencies is assumed to form the basis of much of this variation, recent work in telomere biology provides evidence for a mechanism of intergenerational plasticity that could lead to rapid changes in maintenance effort in response to shifts in reproductive scheduling. Telomere shortening places limits on cell division, and is thought to contribute to impairment of cell proliferation-dependent traits such as immunity and tissue repair, and thereby to accelerate senescence. Unlike the telomere length (TL) attrition that occurs with age in most tissues, sperm are the only cell type in which TL increases with age. Because telomeres are DNA, any lengthening of sperm TL due to delayed reproduction should be passed on to offspring with high fidelity, leading to the hypothesis that multi-generational secular trends towards older paternal age at conception (PAC) will result in cumulative and rapid lengthening of inherited TL. Although PAC in any one generation will vary due to birth order and other factors, the cumulative multi-generational character of the PAC effect could lead to a more stable, and thus reliable, indicator of age at reproduction in recent ancestors--thus providing a useful signal from which to calibrate patterns of resource allocation that influence the pace of aging. Recent pilot data demonstrated this cumulative PAC effect across two generations living in Cebu, the Philippines. However, it remains unclear how many generations the PAC effect on TL persists, and thus, how deep and integrative the historical demographic signal conveyed via TL is. This project will therefore 1) examine the intergenerational stability of the PAC effect on descendants' TL across four generations; 2) characterize the sex-specific heritability patterns of TL; and 3) assess possible fitness impacts of inherited TL as reflected in early life infectious disease related morbidity and mortality.
在美国和许多其他国家,人们越来越多地推迟到晚年才开始组建家庭。相应地,人们越来越关注父母的年龄对后代生物学的影响。这项研究检查了一个重要的衰老遗传标记,端粒长度,这被认为是受父亲年龄的影响。 端粒是覆盖染色体末端的DNA,并且随着细胞复制、氧化应激和年龄而缩短。 与其他研究结果相反,年长的父亲年龄可能对端粒长度有积极的影响,促进后代长寿。这项提案将收集家谱历史并测量端粒长度,以便更好地辨别父亲的年龄是否真的影响端粒长度,以及这种影响是否在几代人之间持续存在(例如,祖父的年龄或曾祖父的生育年龄是否影响后代的端粒长度)。此外,这项提案将研究端粒长度是否会影响除衰老外的早期免疫功能。因此,这些调查将有助于更广泛地了解人类生活史的演变。更广泛的影响包括产生与人类生物学家和公共卫生研究人员相关的有价值的共享数据集,以及将项目分析和数据纳入学生培训,指导和课程。衰老的进化模型假设,当个体在高龄繁殖时,选择将有利于增加维持努力和相应的衰老减缓。模式生物的种间比较和选择实验表明,较低的死亡率/较晚的繁殖年龄与寿命延长有关,广泛支持这些理论预期。虽然自然选择对基因频率的作用被认为是形成这种变异的基础,但最近在端粒生物学方面的研究为代际可塑性机制提供了证据,这种机制可能导致维持努力的快速变化,以应对生殖时间表的变化。端粒缩短限制了细胞分裂,并被认为有助于损害细胞增殖依赖性特征,如免疫和组织修复,从而加速衰老。与大多数组织中随年龄增长而发生的端粒长度(TL)磨损不同,精子是TL随年龄增长的唯一细胞类型。由于端粒是DNA,任何延长的精子TL由于延迟繁殖应传递给后代的高保真度,导致多代长期趋势的父亲年龄在概念(PAC)将导致累积和快速延长的遗传TL的假设。虽然PAC在任何一代都会因出生顺序和其他因素而有所不同,但PAC效应的累积多代特征可能会导致最近祖先生殖年龄的更稳定,因此更可靠的指标-从而提供了一个有用的信号,以校准影响老龄化速度的资源分配模式。最近的试点数据表明,这种累积PAC效应跨越两代人生活在菲律宾的宿务。然而,目前尚不清楚PAC对TL的影响持续了多少代,因此,通过TL传达的历史人口信号有多深和综合性。因此,本项目将1)检查PAC对后代四代TL影响的代际稳定性; 2)描述TL的性别特异性遗传力模式; 3)评估遗传TL可能的健身影响,反映在生命早期传染病相关的发病率和死亡率。

项目成果

期刊论文数量(0)
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Daniel Eisenberg其他文献

376. Subcortical Contributions to the Explore-Exploit Tradeoff
  • DOI:
    10.1016/j.biopsych.2017.02.393
  • 发表时间:
    2017-05-15
  • 期刊:
  • 影响因子:
  • 作者:
    Bruno Averbeck;Vincent Costa;Daniel Eisenberg;Jasmin Czarapata;Karen Berman;Elizabeth Murray
  • 通讯作者:
    Elizabeth Murray
23. Longitudinal Characterization of White Matter Myelination in Vivo in the Healthy Human Brain a From Childhood to Adulthood
  • DOI:
    10.1016/j.biopsych.2023.02.206
  • 发表时间:
    2023-05-01
  • 期刊:
  • 影响因子:
  • 作者:
    Jesse M. Oler;Michael D. Gregory;J. Shane Kippenhan;Shau-Ming Wei;Tiffany Nash;Daniel Eisenberg;Katherine Cole;Peter Schmidt;Karen F. Berman
  • 通讯作者:
    Karen F. Berman
P677. Sex-Specific Polygenic Regulation of Dopamine Synthesis in Striatum in Vivo
  • DOI:
    10.1016/j.biopsych.2022.02.914
  • 发表时间:
    2022-05-01
  • 期刊:
  • 影响因子:
  • 作者:
    Stuti Bansal;Daniel Eisenberg;Michael Gregory;Madeline Hamborg;Philip D. Kohn;Jasmin B. Czarapata;Bhaskar Kolachana;Karen Berman
  • 通讯作者:
    Karen Berman
P443. Longitudinal Trajectories of Myelin Development in Children With Williams Syndrome
  • DOI:
    10.1016/j.biopsych.2022.02.679
  • 发表时间:
    2022-05-01
  • 期刊:
  • 影响因子:
  • 作者:
    Jonathan Kippenhan;Michael Gregory;Tiffany Nash;Shau-Ming Wei;Katherine (Reding) Cole;Madeline Hamborg;Andrea E. Gouvea;Stuti Bansal;Zachary Trevorrow;Oriana Myers;Daniel Eisenberg;Carolyn B. Mervis;Karen Berman
  • 通讯作者:
    Karen Berman
Naturally available oils contain phytosterols that affect cholesterol absorption
  • DOI:
    10.1007/s11883-003-0072-4
  • 发表时间:
    2003-01-01
  • 期刊:
  • 影响因子:
    5.200
  • 作者:
    Daniel Eisenberg
  • 通讯作者:
    Daniel Eisenberg

Daniel Eisenberg的其他文献

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{{ truncateString('Daniel Eisenberg', 18)}}的其他基金

Doctoral Dissertation Research: Evolutionary Perspectives on Microchimerism
博士论文研究:微嵌合现象的进化观点
  • 批准号:
    1751388
  • 财政年份:
    2018
  • 资助金额:
    $ 35.27万
  • 项目类别:
    Standard Grant
EAPSI: Resilience of the South Korean electric grid to disasters: Development of socio-infrastructure network models
EAPSI:韩国电网的抗灾能力:社会基础设施网络模型的开发
  • 批准号:
    1415060
  • 财政年份:
    2014
  • 资助金额:
    $ 35.27万
  • 项目类别:
    Fellowship Award

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  • 批准号:
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  • 批准号:
    31024801
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    2010
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    24.0 万元
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    专项基金项目
Computational Methods for Analyzing Toponome Data
  • 批准号:
    60601030
  • 批准年份:
    2006
  • 资助金额:
    17.0 万元
  • 项目类别:
    青年科学基金项目

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Structural and Biological Effects of Ribonucleotide Insertion into Telomeres
核糖核苷酸插入端粒的结构和生物学效应
  • 批准号:
    10750783
  • 财政年份:
    2023
  • 资助金额:
    $ 35.27万
  • 项目类别:
CSHL 2023 Conference on Telomeres & Telomerase
CSHL 2023端粒会议
  • 批准号:
    10671999
  • 财政年份:
    2023
  • 资助金额:
    $ 35.27万
  • 项目类别:
Genetic and environmental factors affecting alternative lengthening of telomeres
影响端粒选择性延长的遗传和环境因素
  • 批准号:
    10684837
  • 财政年份:
    2022
  • 资助金额:
    $ 35.27万
  • 项目类别:
Genetic and environmental factors affecting alternative lengthening of telomeres
影响端粒选择性延长的遗传和环境因素
  • 批准号:
    10539385
  • 财政年份:
    2022
  • 资助金额:
    $ 35.27万
  • 项目类别:
Architecture and mechanism of the shelterin complex
庇护所综合体的结构和机制
  • 批准号:
    21K20645
  • 财政年份:
    2021
  • 资助金额:
    $ 35.27万
  • 项目类别:
    Grant-in-Aid for Research Activity Start-up
RPA and RPA-like Complexes at Telomeres
端粒上的 RPA 和类 RPA 复合物
  • 批准号:
    10404051
  • 财政年份:
    2020
  • 资助金额:
    $ 35.27万
  • 项目类别:
Structural Biology of Tetrahymena Telomerase Interactions at Telomeres
四膜虫端粒酶在端粒相互作用的结构生物学
  • 批准号:
    2016540
  • 财政年份:
    2020
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    $ 35.27万
  • 项目类别:
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RPA and RPA-like Complexes at Telomeres
端粒上的 RPA 和类 RPA 复合物
  • 批准号:
    10626908
  • 财政年份:
    2020
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    $ 35.27万
  • 项目类别:
RPA and RPA-like Complexes at Telomeres
端粒上的 RPA 和类 RPA 复合物
  • 批准号:
    10212427
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    2020
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    $ 35.27万
  • 项目类别:
RPA and RPA-like Complexes at Telomeres
端粒上的 RPA 和类 RPA 复合物
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    10808715
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    2020
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