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Is the error in telomere length measurement introduced by EBV-immortalization of DNA random or systematic?: A Pilot Feasibility Study

a PSC Research Project

Investigator:   Arline T. Geronimus

Determining how social processes work through biological mechanisms to impact health is fundamental to understanding population health and aging disparities. Telomere length in a subset of leukocytes called peripheral blood mononuclear cells (PBMC) has emerged as an intriguing new biomeasure of aging and stress, with growing interest in its use as a marker of the toll that cumulative stress takes on the body- a biological rather than chronological age marker. The "gold standard" for measuring telomere length is to use fresh venous blood cells. Yet,primary data collection including venous blood draws for population-level research is prohibitive. Ongoing major national data collection activities are increasingly isolating DNA and storing it in specimen repositories after the cells have been immortalized using Epstein-barr virus (EBV). Whether or not immortalized cells are valid for telomere measurement is subject to debate, but ultimately an empirical question. We seek pilot funding to perform a feasibility study needed to strengthen a revised NIH proposal for resubmission. The aims of the original proposal were (1) to estimate the validity of using DNA that has been immortalized using EBV for storage in specimen repositories in studies of black-white differences in telomere length; and (2) if a valid approach, to estimate what size samples are necessary to employ in such studies, taking the error introduced by cell immortalization into account. These are important methodological questions that have yet to be addressed. If our findings validate the use of immortalized cells for telomere length measurement, they will immediately open up opportunities for researchers to use stored DNA appended to national data sets, to test complex hypotheses related to population disparities in health and aging and the biological mechanisms that underlie them, while employing sufficiently powered sample sizes.The pilot funding we request would support a “dry run” of all proposed procedures on a small sample of black and white women to provide preliminary findings demonstrating that the proposed lab work can be carried out successfully at the University of Michigan, and to fine-tune recruitment, survey, blood collection, and bench work protocols before embarking on the much larger project.

Funding Period: 07/01/2011 to 06/30/2012

Country of Focus: USA

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