Leukocyte Telomere Length and Lens Tansparency as Biomarkers in Population Studies of Human AgingSanders, Jason (2012) Leukocyte Telomere Length and Lens Tansparency as Biomarkers in Population Studies of Human Aging. Doctoral Dissertation, University of Pittsburgh. (Unpublished)
AbstractBiomarkers of aging are indicators of characteristics of an organism which change over time. Validating aging biomarkers will enable researchers to better understand aging mechanisms and design interventions which promote healthy aging. This dissertation uses population-based cohorts to explore two emerging biomarkers of human aging, leukocyte telomere length (LTL) and lens transparency. Short LTL records systemic oxidation and inflammation and contributes to cellular senescence. Previous studies focused on its association with diagnosed age-related chronic disease in one physiologic system and have generated equivocal results. Because disease can be undiagnosed and exist in several tissues simultaneously, previous research may have underestimated associations with LTL. We studied the association of LTL with an index of disease burden, which tabulates age-related chronic disease in five physiologic systems regardless of diagnosis. To the extent that an index across systems might capture an underlying propensity to age-related changes in all systems, a marker of fundamental aging processes such as LTL should be associated with it. We show LTL is associated with this index of disease burden. Thus, LTL might indicate widespread incremental changes in structure or function in older adults independent of diagnosed disease. Lens transparency may reflect systemic load of molecular glycation and denaturation, which have been associated with aging. Correlates of reduced lens transparency in humans are undefined. We studied the association of lens transparency to markers of aging and disease. We found that older adults with highly transparent lenses have longer LTL, lower prevalence of diabetes, better cognition, and lower odds of an ApoE4 allele, the strongest genetic risk factor for Alzheimer’s disease. Transparency is unrelated to risk factors for atherosclerosis or non-invasively measured vascular disease. What are the public health implications of this work? First, LTL may aid in the development of screening tools and interventions to prevent age-related disease simultaneously in multiple physiologic systems. Second, lens transparency may help detect amyloid-related brain pathology, which is vital to developing interventions to slow brain aging. Future epidemiologic research should focus on correlating changes in LTL and transparency to changes in age-related phenotypes and the ability of LTL and transparency to predict age-related outcomes. Share
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