HRT 'protects' against rapid ageing that may be linked to Alzheimer's disease, study finds The effect was seen in healthy menopausal women carrying a well-known Alzheimer's gene. Scientists looked for a genetic hallmark of unusually rapid biological ageing in blood samples taken from the women. They found that HRT appeared to slow down the cellular "clock" in at-risk women with the Alzheimer's gene ApoE4. Treated women showed no evidence of the accelerated ageing seen in those not given hormone replacement. The research, published in the online journal Public Library of Science ONE, indicates that rapid biological ageing might be associated with Alzheimer's in some women. At the same time, it points to a simple way of preventing it. Study leader Professor Natalie Rasgon, from Stanford University in California, US, said: "This shows that ApoE4 is contributing to ageing at the cellular level well before any outward symptoms of decline become apparent. Yet, oestrogen appears to have a protective effect for middle-aged women who are carrying this genetic risk factor. Numerous previous studies have suggested that ApoE4 contributes to age-related mental decline and Alzheimer's disease. The gene variant is present in about 40% of people with late-onset Alzheimer's. Prof Rasgon's team focused on telomeres - caps on the ends of chromosomes that keep DNA stable and act like genetic fuses. Every time a cell divides, its telomeres shorten. If they become too short, the cell can die or lose its ability to divide further. This translates to visible signs of ageing, such as wrinkled skin, and other harmful effects within the body. Telomere shortening varies between individuals and can be used as a measure of biological ageing. The scientists analysed telomeres from white blood cells in samples taken from almost 70 healthy women, mostly aged between 45 and 65, who were on HRT Women were randomly divided into two groups. One remained on hormone therapy while the other halted treatment. Two years later, the telomeres were checked again and the researchers calculated the rate at which their length had changed. The telomeres of women carrying the Alzheimer's gene were six times more likely than those of non-carriers to have undergone significant shortening over the two year period. On average, telomeres of women with ApoE4 had shortened by an amount that would normally be expected in a decade. The women had effectively aged five times faster than non-carriers. But HRT cancelled out the negative influence of the gene on telomere length. Women with ApoE4 who continued to have hormone replacement showed no evidence of rapid telomere shortening. "Our take-home findings from this study were first, that ApoE4 carriers are at greater risk of biological ageing, which is associated with negative health outcomes, and second, that if you were a post-menopausal ApoE4 carrier, being on oestrogen therapy was a good thing for telomere length, an established measure of biological ageing at the cellular level," Prof Rasgon said. This brings us a step closer to being able to identify which women will benefit the most from oestrogen replacement therapy. Dr Simon Ridley, from the charity Alzheimer's Research UK, said: "Although this small study did not investigate whether HRT could prevent Alzheimer's or measure its effects on cognition, the results could provide a useful new lead for research in this complex area. Currently there is mixed evidence surrounding the effects of HRT on Alzheimer's risk, and some research suggests the timing of HRT may be important. Ultimately, we'd need to see large-scale, long-term trials to know whether HRT can prevent Alzheimer's, and how the effects of this therapy might differ depending on our genetic make-up. We still need to know much more about the ApoE4 risk gene, and this study has suggested important new clues about its possible effects. While it's not clear how the process of cell ageing might be linked to Alzheimer's, these results could eventually help scientists better understand the causes of the disease. Alzheimer's is the most common cause of dementia, which affects 820,000 in the UK today, and we urgently need treatments that can tackle the disease.