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，是正常细胞分裂所必需的。这种缩短与细胞增殖能力下降有关，这被认为是导致衰老的原因。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，赶超生长加速端粒耗竭。尽管端粒具有进化和健康相关的意义，但在非西方环境中或从人类学/进化的角度对它们进行的研究很少。研究人员正在研究世界各地9个种群中母亲及其后代LTL的种群差异。他们将跨人群数据的广度与菲律宾26年的多代纵向数据相结合，为几个相关假设提供了补充见解。具体来说，他们正在测试已知影响细胞增殖与LTL的传染性和营养压力源之间的假设。这项研究将提供在生态条件差异很大的人群中LTL的一些第一个比较数据，并且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措施与成年LTL联系起来的研究。通过调节细胞和组织维持的支出，端粒长度可能是一个重要的生活史分配机制。通过追踪端粒长度对生态应激源的发育反应，该研究有助于深入了解早期生活环境与后期生理编程之间的可能机制。这笔资助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与全球头号杀手心血管疾病有关。通过使用纵向数据阐明LTL的发展预测因素，本研究将为快速发展的文献提供新的见解，这些文献将经济和生活方式快速转变的社会中的早期生活经历与成年慢性病联系起来。

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.