Apolipoprotein-?4 (APOE-?4) 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-?4 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-?4 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-?4 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-?4 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-?4 carriers who went off their HT regimen exhibited TL shortening, as predicted for the at-risk population. APOE-?4 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.
View details for DOI 10.1371/journal.pone.0054713
View details for Web of Science ID 000315970300020
View details for PubMedID 23418430