Impact of Metals on Biological Aging and Cardiometabolic Traits in Adolescents

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ABSTRACT The ubiquitous presence of toxic metal exposures in the environment is a global public health concern, with disadvantaged populations disproportionately exposed and susceptible to adverse effects. Lead, arsenic, cadmium, and mercury are the most commonly occurring toxic environmental metal exposures in the general population. These metal exposures appear among the top 7 of the Agency for Toxic Substances and Disease Registry Substance Priority List, prioritizing substances based on a combination of their frequency, toxicity, and potential for human exposure. Observations from population studies support associations between these metal exposures and cardiovascular diseases in adulthood; however, the literature is sparse for early life cardiometabolic health impacts. Research on the childhood origins of cardiovascular diseases shows that early life factors influence cardiovascular risk over the life course, with adolescence a sensitive developmental environmental factors eliciting biological aging, such as alterations to supporting these as mechanisms for understanding how early life metal exposures can affect cardiometabolic health. period for establishing cardiometabolic phenotype trajectories. There is emerging evidence of DNA methylation and telomere length, thus Addressing gaps in the current scientific literature will improve exposure remediation and risk reduction strategies in the most vulnerable populations and provide support for new disease prevention opportunities. The proposed epidemiologic research will provide insights on the (1) early-life health effects of metal exposures, (2) impacts of metal co-exposures, (3) adolescence as a sensitive period for cardiometabolic phenotype programming, and (4) mechanisms of action by which metal exposures cause cardiometabolic dysfunction. This study's overall goal is to evaluate the effect of metal co-exposures on cardiometabolic trait trajectories and biological aging during adolescence. We will leverage the established Bangladesh Environmental Research in Children's Health (BiRCH) cohort, comprised of 500 youth residing in rural Bangladesh. Enrolled participants will be aged 11 to 13 years at the time of the proposed first research visit. We propose the following specific aims: (1) to evaluate the association of metal exposures with longitudinal cardiometabolic traits during adolescence; (2) to evaluate the association of metal exposures with changes in DNA methylation and DNA methylation age during adolescence; (3) to evaluate the association of metal exposures with changes in leukocyte telomere length during adolescence. The proposed epidemiologic research during adolescence will provide new data to unravel the effects of metal exposures on cardiovascular diseases' pathogenesis in very early stages. This research may offer novel findings for DNA methylation and telomere length as biosensors of metal exposures, leveraged in future studies to identify individuals at high risk of cardiometabolic dysfunction and other relevant adverse health outcomes.