Accelerated cell aging in female APOE-ε4 carriers: implications for hormone therapy use

TitleAccelerated cell aging in female APOE-ε4 carriers: implications for hormone therapy use
Publication TypeJournal Article
Year of Publication2013
AuthorsJacobs EG, Kroenke C, Lin J, Epel ES, Kenna HA, Blackburn EH, Rasgon NL
JournalPLoS One
Volume8
Issue2
Paginatione54713
Date Published2013
ISSN1932-6203
KeywordsAlleles, Alzheimer Disease, Apolipoprotein E4, Cell Aging, Cognition Disorders, Female, Genetic Predisposition to Disease, Genotype, Heterozygote, Hormone Replacement Therapy, Humans, Logistic Models, Middle Aged, Neuropsychological Tests, Postmenopause, Risk Factors, Telomere Shortening
Abstract

Apolipoprotein-ε4 (APOE-ε4) is a major genetic risk factor for cognitive decline, Alzheimer's disease (AD) and early mortality. An accelerated rate of biological aging could contribute to this increased risk. Here, we determined whether APOE-ε4 status impacts leukocyte telomere length (TL) and the rate of cellular senescence in healthy mid-life women and, further, whether hormone replacement therapy (HT) modifies this association. Post-menopausal women (N = 63, Mean age = 57.7), all HT users for at least one year, were enrolled in a randomized longitudinal study. Half of the participants (N = 32) remained on their HT regimen and half (N = 31) went off HT for approximately two years (Mean  = 1.93 years). Participants included 24 APOE-ε4 carriers and 39 non-carrier controls. Leukocyte TL was measured at baseline and the end of year 2 using quantitative polymerase chain reaction. Logistic regression analysis indicated that the odds of an APOE-ε4 carrier exhibiting telomere shortening (versus maintenance/growth) over the 2-year study were more than 6 (OR  = 6.26, 95% CI  = 1.02, 38.49) times higher than a non-carrier, adjusting for established risk factors and potential confounds. Despite the high-functioning, healthy mid-life status of study participants, APOE-ε4 carriers had marked telomere attrition during the 2-year study window, the equivalent of approximately one decade of additional aging compared to non-carriers. Further analyses revealed a modulatory effect of hormone therapy on the association between APOE status and telomere attrition. APOE-ε4 carriers who went off their HT regimen exhibited TL shortening, as predicted for the at-risk population. APOE-ε4 carriers who remained on HT, however, did not exhibit comparable signs of cell aging. The opposite pattern was found in non-carriers. The results suggest that hormone use might buffer against accelerated cell aging in mid-life women at risk for dementia. Importantly, for non-carrier women there was no evidence that HT conferred protective effects on telomere dynamics.

DOI10.1371/journal.pone.0054713
Alternate JournalPLoS ONE
PubMed ID23418430
PubMed Central IDPMC3572118
Grant ListM01 RR-00070 / RR / NCRR NIH HHS / United States
R01 AG22008 / AG / NIA NIH HHS / United States