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The rate of leukocyte telomere shortening predicts mortality from cardiovascular disease in elderly men

Elissa S. Epel¹, Sharon Stein Merkin², Richard Cawthon³, Elizabeth H. Blackburn⁴, Nancy E. Adler¹, Mark J. Pletcher⁵ and Teresa E. Seeman² ¹University of California, San Francisco, Department of Psychiatry, San Francisco, CA, 94143, USA ²University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, CA, 90095-1687, USA ³University of Utah, Human Genetics, Salt Lake City, UT 84112, USA 4University of California, San Francisco, Department of Biochemistry & Biophysics, San Francisco, CA, 94158, USA ⁵University of California, San Francisco, Department of Epidemiology & Biostatistics, San Francisco, CA, 94107, USA Running title: Telomere Shortening and Mortality Key words: aging, longevity, telomere length, cardiovascular disease, mortality Received: 11/05/08; accepted: 12/01/08; published on line: 12/19/08 Correspondence: Elissa S. Epel, PhD, University of California, San Francisco, Department of Psychiatry, 3333 California St, Ste. 465, San Francisco, CA, 94143, USA e-mail: EEpel@lppi.ucsf.edu


Abstract


Telomere length (TL) has been proposed as a marker of mitotic cell age and as a general index of human organismic aging. Short absolute leukocyte telomere length has been linked to cardiovascular-related morbidity and mortality. Our aim was to test whether the rate of change in leukocyte TL is related to mortality in a healthy elderly cohort. We examined a subsample of 236 randomly selected Caucasian participants from the MacArthur Health Aging Study (aged 70 to 79 years). DNA samples from baseline and 2.5 years later were assayed for mean TL of leukocytes. Percent change in TL was calculated as a measure of TL change (TLC). Associations between TL and TLC with 12-year overall and cardiovascular mortality were assessed. Over the 2.5 year period, 46% of the study participants showed maintenance of mean bulk TL, whereas 30% showed telomere shortening, and, unexpectedly, 24% showed telomere lengthening. For women, short baseline TL was related to greater mortality from cardiovascular disease (OR = 2.3; 95% CI:1.0-5.3). For men, TLC (specifically shortening), but not baseline TL, was related to greater cardiovascular mortality, OR = 3.0 (95% CI: 1.1-8.2). This is the first demonstration that rate of telomere length change (TLC) predicts mortality and thus may be a useful prognostic factor for longevity.

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