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

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减弱有关，这被认为是导致衰老的原因之一。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，追赶生长加速了端粒的枯竭。尽管端粒具有进化和与健康相关的意义，但在非西方环境中或从人类学/进化论的角度对端粒进行研究的人很少。研究人员正在研究来自世界各地的9个群体的母亲及其后代的LTL的群体变异。他们将这种跨人口数据的广度与菲律宾26年来多代人的纵向数据结合在一起，为几个相关的假设提供了补充的见解。具体地说，他们正在测试将已知的影响细胞增殖的感染和营养应激源与LTL联系起来的假设。这项研究将提供一些关于生态条件差异很大的种群中LTL的第一个比较数据，并将是我们所知的第一个使用纵向数据将早期生命免疫激活的测量与成人LTL联系起来的研究。通过调节细胞和组织维持的支出，端粒长度可能是一种重要的生活史分配机制。通过跟踪端粒长度对生态应激源的发育反应，这项研究有助于深入了解将早期生活环境与后期生活生理学编程联系起来的可能机制。这笔赠款将用于培训一名博士生，同时也有助于促进与菲律宾研究人员的合作。此外，LTL与心血管疾病有关，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，这项研究将为快速扩张的文献提供新的见解，这些文献将早期生活经历与正在经历快速经济和生活方式转型的社会中的成人慢性病联系起来。

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.