Doctoral Dissertation Improvement: Cross-Population and Longitudinal Predictors of Telomere Length Variation: Do Infectious Exposure and Catch-Up Growth Make a Difference?

博士论文改进：端粒长度变异的跨群体和纵向预测因子：感染性暴露和追赶性生长有影响吗？

• 批准号: 0962282
• 负责人: Christopher Kuzawa
• 金额: $ 2万
• 依托单位: Northwestern University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-15 至 2013-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0962282&HistoricalAwards=false
• 关键词: Doctoral; Dissertation; Improvement; Cross; Population

Telomeres are DNA sequences at chromosome ends that shorten with age and are required for proper cell division. This shortening is associated with diminished cell proliferation capacity, which is believed to contribute to aging. Leukocyte telomere length (LTL) is thought to reflect previous immune system activation and current/reserved immune function. It has also been proposed that catch-up growth accelerates telomere depletion. Despite the evolutionary and health-related significance of telomeres, they have been little examined in non-western environments or from an anthropological/evolutionary perspective. The researchers are examining population variation in LTL in mothers and their offspring across nine populations from around the world. They combine the breadth of this cross-population data with 26 years of multi-generational longitudinal data from the Philippines, providing complementary insights into several related hypotheses. Specifically, they are testing hypotheses linking infectious and nutritional stressors known to influence cellular proliferation with LTL. This study will provide some of the first comparative data on LTL in populations varying widely in ecological conditions, and will be the first to our knowledge to use longitudinal data to link measures of early life immune activation with adult LTL. By modulating expenditure on cellular and tissue maintenance, telomere length may be an important life-history allocation mechanism. By tracking the developmental responses of telomere lengths to ecological stressors, the study contributes insights into a possible mechanism linking early life environment with programming of later-life physiology. This grant will be used to train a PhD student, while also helping foster collaborations with Filipino researchers. Further, LTLs are associated with cardiovascular disease, the number one global killer. By clarifying developmental predictors of LTL using longitudinal data, this study will contribute new insights into the rapidly-expanding literature linking early life experiences with adult chronic disease in societies experiencing rapid economic and lifestyle transitions.

端粒是染色体末端的DNA序列，随着年龄的增长而缩短，是细胞正常分裂所必需的。这种缩短与细胞增殖能力降低有关，这被认为有助于衰老。白细胞端粒长度（LTL）被认为反映了先前的免疫系统激活和当前/保留的免疫功能。也有人提出追赶生长加速端粒耗竭。尽管端粒的进化和健康相关的意义，他们很少在非西方环境或从人类学/进化的角度进行研究。研究人员正在研究来自世界各地的9个种群的母亲及其后代的LTL的种群差异。他们联合收割机结合了这一跨人群数据的广度和菲律宾26年多代纵向数据，为几个相关假设提供了补充见解。具体来说，他们正在测试将已知影响细胞增殖的感染和营养应激因素与LTL联系起来的假设。这项研究将提供一些在生态条件变化很大的人群中的LTL的第一个比较数据，并将是第一个我们所知的使用纵向数据来连接的措施，早期生活的免疫激活与成人LTL。通过调节细胞和组织维持的消耗，端粒长度可能是一个重要的生活史分配机制。通过跟踪端粒长度对生态压力的发育反应，该研究有助于深入了解早期生活环境与后期生活生理学编程之间的可能机制。这笔赠款将用于培养一名博士生，同时也有助于促进与菲律宾研究人员的合作。此外，LTL与心血管疾病相关，心血管疾病是全球头号杀手。通过使用纵向数据澄清LTL的发展预测因素，本研究将为快速扩展的文献提供新的见解，这些文献将经历快速经济和生活方式转变的社会中的早期生活经历与成人慢性病联系起来。