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 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.
Ms Rasgon added: "This brings us a step closer to being able to identify which women will benefit the most from oestrogen replacement therapy."