RUI: Telomere Dynamics and Individual Quality

RUI：端粒动态和个体品质

• 批准号: 0516784
• 负责人: Robert Mauck
• 金额: $ 53.52万
• 依托单位: Kenyon College
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0516784&HistoricalAwards=false
• 关键词: RUI; Telomere; Dynamics; Individual; Quality

Telomere Dynamics and Individual QualityRobert A. Mauck and Mark F. Haussmann Kenyon CollegeTelomeres are repeated DNA sequences at the termini of eukaryotic chromosomes that function to protect and stabilize DNA. Telomeres generally shorten over time from incomplete replication during cell division and oxidative damage. Thus, they have been linked to cellular senescence. Within species, there is evidence that telomere length is positively correlated with survival and, thus, individual quality and longevity. In a study cited by Discover Magazine as one of the Top 100 Science Stories of 2003, Haussmann and colleagues found an exception to this general rule. The telomeres of Leach's storm-petrels (Oceanodroma leucorhoa) apparently lengthen with age. One explanation for this unique finding is that these long-lived birds have found a way to lengthen their telomeres. Significantly for aging research, if the finding can be verified it would be the first report of telomere elongation.Recent evidence indicates that age-specific reproductive success in these same birds can in large part be attributed to differences in individual quality. Mauck and colleagues recently demonstrated a positive correlation between reproductive success in the first breeding year and longevity. This positive correlation between reproductive success and adult survivorship defines individual quality as predicted by the Selection Hypothesis, which attributes age-related variation in reproductive success to intrinsic variation between individuals rather than to changes within individuals over time. The Selection Hypothesis offers an alternative explanation for the observed correlation between telomere length and age in storm-petrels. Essentially, if initial telomere length is correlated with individual quality and only high quality individuals reach advanced age, then mean telomere length should increase with age since only individuals born with long telomeres reach old age.This project tests whether the observed positive correlation between telomere length and age can be attributed to lengthening of telomeres (Elongation Hypothesis) or to intrinsic differences between individuals (Selection Hypothesis) with regard to initial telomere length and mechanisms of telomere shortening and maintenance. The same population of storm-petrels that produced evidence of telomere lengthening and variation in individual quality will be used to test mutually exclusive predictions from the Elongation and Selection Hypotheses with regard to the phenomenon of age-specific telomere length. The researchers will use both natural and experimental variation in chick nutritional condition to examine the dynamics of telomere shortening and maintenance during the two-month chick development period when rate of telomere change is highest. Trained undergraduates will assist in examining effects of early life environment on how oxidative damage, anti-oxidant levels, and telomerase activity influence the net change in telomere length. The proposal builds on Kenyon College's strong commitment to undergraduate research and mentoring in the biological sciences. Students will be involved in field and lab research as part of Kenyon's Summer Science Scholar Program and honors theses. A new course will be offered at Kenyon that parallels concepts and techniques outlined in the proposal. The course will be taught by Haussmann (in collaboration with Mauck) as part of a post-doctoral fellowship combining research with teaching, thereby training a beginning scientist in balancing the demands of research and teaching at a high-quality liberal arts institution. Finally, the research enhances our understanding of aging with regard to telomere biology and provides an alternative model system for the study of individual variation in aging and senescence, a contrast to existing systems focused on short-lived species.

端粒动态与个体素质Mauck和Mark F.端粒是真核生物染色体末端的重复DNA序列，具有保护和稳定DNA的功能。端粒通常在细胞分裂和氧化损伤期间由于不完全复制而随着时间缩短。因此，它们与细胞衰老有关。在物种内部，有证据表明端粒长度与生存呈正相关，从而与个体质量和寿命呈正相关。在一项被《发现》杂志列为2003年100大科学故事之一的研究中，豪斯曼和他的同事发现了这一普遍规律的一个例外。Leach的风暴海燕（Oceanodroma leucorhoa）的端粒显然随着年龄的增长而延长。对这一独特发现的一种解释是，这些长寿的鸟类找到了一种延长端粒的方法。对于衰老研究来说，如果这一发现得到证实，这将是第一个端粒延长的报告。最近的证据表明，这些鸟类的年龄特异性繁殖成功在很大程度上归因于个体质量的差异。Mauck及其同事最近证明了第一个繁殖年的繁殖成功与寿命之间的正相关性。繁殖成功和成年生存率之间的正相关性定义了个体质量，正如选择假说所预测的那样，该假说将繁殖成功中与年龄相关的变化归因于个体之间的内在变化，而不是随着时间的推移个体内部的变化。选择假说为观察到的暴风海燕端粒长度和年龄之间的相关性提供了另一种解释。从本质上讲，如果初始端粒长度与个体质量相关，并且只有高质量的个体才能达到高龄，那么平均端粒长度应该随着年龄的增长而增加，因为只有出生时端粒长的个体才会进入老年。本项目测试端粒长度和年龄之间的正相关性是否可以归因于端粒的延长（延伸假说）或个体之间的内在差异（选择假说）关于初始端粒长度和端粒缩短和维持的机制。产生端粒延长和个体质量变化的证据的同一种群的风暴海燕将用于测试关于年龄特异性端粒长度现象的延伸和选择假说的互斥预测。研究人员将利用鸡营养条件的自然和实验变化来研究端粒缩短和维持的动态，在两个月的鸡发育期，端粒变化率最高。受过训练的本科生将协助研究早期生活环境对氧化损伤，抗氧化水平和端粒酶活性如何影响端粒长度的净变化的影响。 该提案建立在凯尼恩学院对生物科学本科生研究和指导的坚定承诺的基础上。学生将参与实地和实验室研究，作为凯尼恩暑期科学学者计划和荣誉论文的一部分。一个新的课程将提供在凯尼恩平行的概念和技术概述的建议。该课程将由豪斯曼（与Mauck合作）教授，作为博士后奖学金的一部分，将研究与教学相结合，从而培养一名科学家在高质量的文科机构中平衡研究和教学的需求。最后，这项研究增强了我们对端粒生物学衰老的理解，并为研究衰老和衰老的个体差异提供了一个替代模型系统，与现有的专注于短命物种的系统形成对比。