Biological aging in early life: exploring developmental and environmental predictors of telomere length and impacts on subclinical atherosclerosis development - Abstract Telomere length (TL), a marker of biological aging located at the ends of chromosomes, is longest at birth and shortens over time. TL in early life is crucial for determining future TL and that TL dynamics during early developmental stages are complex. However, early-life predictors of TL remain poorly understood, as is our understanding of the rate of changes in TL during the first two decades of life and how this biological aging process affect susceptibility to diseases in later life. Shorter TL in adults has been associated with increased atherosclerotic morbidity and mortality, but the role of early-life TL dynamics in the development of subclinical atherosclerosis remains unclear. The overall objective of this study is to understand how key growth and environmental factors shape early-life TL and to determine the impact of TL and its changes from birth to young adulthood on subclinical atherosclerosis development. Utilizing data from the Southern California Children's Health Study, a longitudinal cohort, we will measure TL from stored biospecimens collected at birth (n = 1,297), age 8 (n = 1,297), and age 24 (n = 400). This project will efficiently leverage a wealth of existing resources including growth data from birth records and annual measurements, ambient and traffic-related air pollution exposure based on lifelong residential history and environmental monitoring data, and subclinical atherosclerosis indicators using carotid ultrasound measures—including carotid intima-media thickness, vascular stiffness, and lipid deposition—collected at ages 11 and 24 years. Specifically, we will determine the extent to which TL and its change from birth to adulthood are affected by growth (Aim 1) and exposure to air pollution (Aim 2). Our working hypothesis is that higher birth weight, higher BMI growth rate across early life course, and early obesity (for Aim 1), as well as lifetime air pollution exposures (for Aim 2), particularly during some sensitive windows (e.g., early childhood, puberty) can shorten TL and accelerate its rate of change from birth through childhood and young adulthood. We will also evaluate the impact of TL and its rate of change from birth to adulthood on subclinical measures of atherosclerosis development from ages 10 to 24 (Aim 3). Our working hypothesis is that shorter TL and faster rate of TL shortening from birth to young adulthood are associated with higher attained subclinical atherosclerotic indicators at ages 10 and 24 and higher rate of change in these measures from age 10 to 24. This project is poised to provide comprehensive insights into how early-life TL is shaped by growth and environmental factors, and how it can impact the progression of subclinical atherosclerosis. Our findings will inform how early changes in biological aging markers may respond to growth and environmental stressors and may subsequently influence the development of aging-related diseases, ultimately offering innovative treatment and prevention strategies to transform public health approaches, targeting the early-life origins of disease with the aim of extending healthy lifespan.
