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Cell ageing slowed by HRT, but only for Alzheimer's risk gene carriers

18 February 2013

By Michelle Downes

Appeared in BioNews 693

Hormone replacement therapy (HRT), used to treat the symptoms of menopause, may play a role in slowing the ageing process in women who carry a certain gene variant, claim scientists. The variant in the gene ApoE4 has previously been associated with an increased risk of developing Alzheimer's disease.

'ApoE4 is contributing to ageing at the cellular level well before any outward symptoms of decline become apparent', said Professor Natalie Rasgon, who led the study at the Stanford School of Medicine. 'Yet, oestrogen appears to have a protective effect for middle-aged women who are carrying this genetic risk factor'.

The study, published in PLOS ONE, included 63 healthy post-menopausal women who had been undergoing HRT for over a year. HRT involves replacing the hormones women lose following menopause, including oestrogen. Of the group of participants, 24 carried the ApoE4 gene variant. The study lasted two years, during which time half of the group discontinued HRT and the other half continued to receive it as usual. The researchers looked at the effects of the treatment on biological ageing.

Telomere shortening can be used as read-out of biological ageing. Telomeres are segments of DNA that protect the genetic information of a cell as it divides. As telomeres become shorter each time a cell divides, they can be used to assess cell age. The participants' telomeres were measured at the beginning and end of the study by analysing blood samples. The change in telomere length indicated the amount of cell ageing that had occurred.

Post-menopausal women who carried the ApoE4 variant were six times more likely to undergo significant shortening in telomere length, suggesting 'ApoE4 carriers are at greater risk of biological ageing, which is associated with negative health outcomes', said lead study author Dr Emily Jacobs of Harvard Medical School. This effect was reduced in women who carried the ApoE4 variant but continued to receive HRT.

In contrast, women who did not carry the ApoE4 variant showed less biological ageing, as determined by a reduction in telomere length, if they stopped receiving HRT. These findings suggest that HRT may have different effects on cell ageing that are dependent on a woman's genetic make-up. 'This brings us a step closer to being able to identify which women will benefit the most from oestrogen replacement therapy', says Dr Jacobs.

'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', said Head of Research at Alzheimer’s Research UK, Dr Simon Ridley, to the Independent. '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'.

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