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Leukocyte Telomere Length and Lens Tansparency as Biomarkers in Population Studies of Human Aging

Sanders, Jason (2012) Leukocyte Telomere Length and Lens Tansparency as Biomarkers in Population Studies of Human Aging. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

Biomarkers 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.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Sanders, Jasonsanders.jason@medstudent.pitt.eduJLS196
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairNewman, Annenewmana@edc.pitt.eduANEWMAN
Committee MemberBoudreau, Robertboudreaur@edc.pitt.eduROB21
Committee MemberKuller, Lewiskuller@edc.pitt.edu
Committee MemberConley, Yvetteyconley@pitt.eduYCONLEY
Committee MemberNiedernhofer, Lauraniedlx@upmc.edu
Date: 2 July 2012
Date Type: Completion
Defense Date: 27 January 2012
Approval Date: 2 July 2012
Submission Date: 15 March 2012
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 189
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Epidemiology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: aging, epidemiology, public health
Date Deposited: 02 Jul 2012 13:25
Last Modified: 15 Nov 2016 13:56
URI: http://d-scholarship.pitt.edu/id/eprint/11449

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