International Research Fellowship Program: Telomere Dynamics: An Important Link Between Growth and Longevity?

该奖项由2009年美国复苏和再投资法案(公法111-5)资助。国际研究奖学金计划使美国科学家和工程师能够在国外进行9至24个月的研究。该计划的奖项提供了联合研究的机会，并利用国外独特或互补的设施、专业知识和实验条件。该奖项将支持布里特·海丁格博士与英国格拉斯哥大学的帕特·莫纳汉博士合作的为期12个月的研究奖学金。越来越多的人认识到，了解生活史特征背后的机制对于预测生活史权衡的演变至关重要。生活史理论预测，生长速度等生活史特征是最优化的，而不是最大化的。支持这一观点的是，在不同的分类群中，快速生长与加速衰老和缩短寿命有关。然而，我们目前对这种联系背后的生理机制知之甚少。在这方面可能特别重要的一个过程是细胞端粒丢失。端粒在细胞分裂过程中缩短，限制了细胞的复制潜力，从而可能影响生物的寿命。在体外暴露于氧化应激会加速端粒的丢失。因此，新陈代谢代价高昂的过程，如生长加速，可能会加速体内端粒的丢失，并在生长速度和寿命之间形成机械联系。这项研究将利用一个独特的机会，在一个已知年龄的、自由生活的长寿海鸟种群中检验这一假设。具体地说，我们将研究1)端粒长度和丢失率是否可以预测寿命，以及2)发育过程中生长加速是否会增加氧化应激水平并加速端粒丢失。这项研究的结果将加强我们对生命早期经历的状况的长期后果的理解，以及生命历史权衡的基础机制。

0852962HeidingerThis award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).The International Research Fellowship Program enables U.S. scientists and engineers to conduct nine to twenty-four months of research abroad. The program's awards provide opportunities for joint research, and the use of unique or complementary facilities, expertise and experimental conditions abroad.This award will support a twelve-month research fellowship by Dr. Britt Heidinger to work with Dr. Pat Monaghan at the University of Glasgow in the UK.There is an increasing appreciation that understanding the mechanisms that underlie life-history traits is essential for predicting the evolution of life-history trade-offs. Life-history theory predicts that life-history traits such as the rate of growth are optimized rather than maximized. In support of this idea, rapid growth is associated with accelerated aging and a reduced lifespan in diverse taxa. However, we currently have little information about the physiological mechanisms that underlie this link. One process that is likely to be particularly important in this regard is cell telomere loss. Telomeres shorten during cell division and limit the replicative potential of cells and might thereby influence organismal lifespan. Exposure to oxidative stress in vitro accelerates telomere loss. Therefore, metabolically costly processes such as growth acceleration might hasten telomere loss in vivo and form a mechanistic link between the rate of growth and longevity. This study will take advantage of a unique opportunity to test this hypothesis in a known-age, free-living population of a long-lived seabird, the European shag (Phalacrocorax aristotelis). Specifically, we will examine whether 1) telomere length and loss rates are predictive of longevity, and whether 2) growth acceleration during development increases levels of oxidative stress and hastens telomere loss. The results of this study will enhance our understanding of the long-term consequences of the conditions experienced during early life and the mechanisms that underlie life-history trade-offs.