DISSERTATION RESEARCH: An Investigation of the Evolution of Telomere Regulation and Longevity

论文研究：端粒调控和寿命进化的调查

• 批准号: 0408008
• 负责人: Carol Vleck
• 金额: $ 1.19万
• 依托单位: Iowa State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-15 至 2006-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0408008&HistoricalAwards=false
• 关键词: DISSERTATION; RESEARCH; Investigation; Evolution; Telomere

This research will investigate the underlying physiological and molecular mechanisms responsible for the wide variation in life spans of different species. One potential mechanism underlying adaptive variation in species maximum lifespan is regulation of telomere dynamics. Telomeres cap the ends of all eukaryotic chromosomes and function in protecting chromosomes and aiding in the completion of duplication. Telomeres shorten with each cell division, however, because of physical limitations of DNA polymerase. Once telomeres shorten to a critical length, cells enter replicative senescence, so while these cells are metabolically active they can no longer divide. Replicative senescence has been suggested as a causal agent of aging and age-related diseases. Previous research has shown that species with longer lifespans lose telomeric repeats at a slower rate than species with shorter lifespans. This suggests that selection may adjust the rate at which telomeres shorten to modify lifespan. This research involves a comparative analysis of 17 bird species that vary in maximum lifespan from 5 to 44 years. It will foster large-scale collaboration between many scientists and promote undergraduate and graduate training in the biology of aging. The results will determine whether telomere regulation has jointly evolved with species maximum lifespan. If so, it will support the hypothesis that telomere regulation acts as a molecular mechanism to adjust lifespan. This project will offer valuable insight into the evolution of mechanisms that influence lifespan.

这项研究将探讨不同物种寿命差异的潜在生理和分子机制。物种最大寿命适应性变化的一个潜在机制是端粒动态调节。端粒覆盖所有真核生物染色体的末端，起保护染色体和帮助完成复制的作用。然而，由于DNA聚合酶的物理限制，端粒随着每次细胞分裂而缩短。一旦端粒缩短到一个临界长度，细胞就进入复制性衰老，所以当这些细胞代谢活跃时，它们就不能再分裂了。复制性衰老被认为是衰老和与年龄有关的疾病的致病因素。先前的研究表明，寿命较长的物种比寿命较短的物种以更慢的速度失去端粒重复序列。这表明，选择可能会调整端粒缩短的速度，以改变寿命。这项研究涉及对17种鸟类的比较分析，这些鸟类的最大寿命从5年到44年不等。它将促进许多科学家之间的大规模合作，并促进衰老生物学的本科生和研究生培训。研究结果将确定端粒调节是否与物种的最大寿命共同进化。如果是这样的话，它将支持端粒调节作为调节寿命的分子机制的假设。这个项目将提供有价值的洞察力的机制，影响寿命的演变。