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

Northwestern University, Evanston IL

Investigators

Abstract

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.