February 18, 2013
ApoE4 Genetic Variant Accelerates Aging In Women

Hormone therapy protects women who carry the ApoE4 genetic variant which is a risk for Alzheimer's. Estrogen can slow aging in the subset of women who carry this genetic variant.

STANFORD, Calif. Healthy menopausal women carrying a well-known genetic risk factor for Alzheimer's disease showed measurable signs of accelerated biological aging, a new study has found.

However, in carriers who started hormone therapy at menopause and remained on that therapy, this acceleration was absent, the researchers said. Hormone therapy for non-carriers of the risk factor, a gene variant called ApoE4, had no protective effect on their biological aging.

"This shows that ApoE4 is contributing to aging at the cellular level well before any outward symptoms of decline become apparent," said Natalie Rasgon, MD, PhD, professor of psychiatry and behavioral sciences at the Stanford University School of Medicine and director of the Stanford Center for Neuroscience in Women's Health. "Yet, estrogen appears to have a protective effect for middle-aged women who are carrying this genetic risk factor."

Another way to read this: personal genomic testing is starting to get useful. Got variant X? Then drug Y is worth the risks it brings.

You can read the full research report at Plos One. The cool part: APOE-ε4 carriers had 5 times the rate of telomere deterioration. Telomeres are chromosome caps that shrink with age. Shroter telomeres are associated with degenerative disease and increased mortality risk.

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.

This is a very important result. Women near and after menopause should seriously consider some cheap genetic testing to use in their deliberations on whether to go on hormone replacement therapy.

Share |      Randall Parker, 2013 February 18 07:46 PM 

destructure said at February 19, 2013 10:10 PM:

There are decades where only a few months worth of advancement are made in a particular field. And then there are months in which decades of advancements are made. Or at least it appears that way. The reason is that science spends decades building up knowledge that it can't use. But then someone makes one final discovery or one crucial breakthrough and suddenly all that knowledge becomes useful. Genetics is where computers were in 1980.

Randall Parker said at February 19, 2013 10:23 PM:


I agree. Here's this study that shows (at least as measured by telomeres) a fraction of women can slow down their rate of aging by a factor of 5 after menopause. That's incredible. I mean, wow.

We'll eventually get useful cell therapies where we can just replace large numbers of our cells that have short telomeres. Pour in cells that will build better vasculature, better skin, better livers, etc. The number of years that happens over will be short as compared to all the decades studying cells and manipulating cells until finally the scientists start making cells dance to our needs.

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