A Study of Rapamycin in the Context of Ovarian Aging

Rapamycin is arguably the best of the calorie restriction mimetic drugs so far tested in mice. It slows aging robustly in animal studies, and has been used in humans at much higher doses than the anti-aging dose (around 5mg once per week) for decades. Still, there is a lack of human trials conducted for the purposes of slowing aspects of aging. More trial data than the little that presently exists would increase the number of physicians willing to prescribe off-label for anti-aging purposes. The specific focus of the trial doesn't much matter so long as the researchers measure enough data to assemble biomarkers of aging and general health. So, for example, one might look at a recently launched study of gum disease in older patients, and the study noted here that is focused on ovarian aging. Both have the potential to produce data relevant to the general question of aging. There are a few more such studies beside these, either planned or in the early stages.

Research into repurposing the immunosuppressant rapamycin has been hailed a "paradigm shift" in how menopause is studied. The Validating Benefits of Rapamycin for Reproductive Aging Treatment (Vibrant) study is designed to measure whether the drug can slow ovaries ageing, thereby delaying menopause, extending fertility and reducing the risk of age-related diseases. The study, which will eventually include more than 1,000 women, now has 34 participants aged up to 35, with more women joining every day.

Early results suggested it was realistic to hope the drug could decrease ovary ageing by 20% without women experiencing any of the 44 side-effects rapamycin can have, which range from mild nausea and headaches to high blood pressure and infections. In fact, participants in the randomised, placebo-controlled study had self-reported improvements in their health, memory, energy levels and in the quality of their skin and hair: health improvements consistent with other studies into rapamycin.

Ovaries release eggs continuously: women lose about 50 every month, with just one reaching ovulation. A small, weekly dose of rapamycin slows ovaries down, so they release only 15 eggs a month. Because rapamycin is a cheap, generic drug already widely used, once the evidence is established, progress will be fast. "The very features of the drug that make it so promising and give it such great potential for having a quick and major impact for women are, ironically, the very factors that make it hard to find funders for the study. That's why this hasn't been done before: it's an expensive study and a lot of women will benefit from it - but there's no motivation for pharmaceutical companies to invest because there's no possibility of making money from an off-patent drug."

A clinical trial of rapamycin in humans has also been considered impossible because it would take decades to detect any longevity effects. Ovaries, however, age so quickly that change can be measured over six months. The level of rapamycin used is small: women are given 5mg a week for three months compared with the 13mg a day that transplant patients can be prescribed for years.

Link: https://www.theguardian.com/society/article/2024/jul/22/drug-women-fertility-study-rapamycin