Research on fruit flies has uncovered how the sex of the individual affects the response to the anti-aging drug rapamycin.
The impact of medications can vary greatly between women and men, and this is also true for the promising anti-aging drug rapamycin, as a recent study from researchers at the Max Planck Institute for Biology of Ageing in Cologne and University College London has shown. The study found that rapamycin only extends the lifespan of female fruit flies, but not that of males.
Additionally, the study revealed that rapamycin only delayed the onset of age-related pathological changes in the gut of female fruit flies. The researchers concluded that biological sex plays a crucial role in determining the effectiveness of anti-aging drugs.
The life expectancy of women is significantly higher than that of men. However, women also suffer more often from age-related diseases and adverse drug reactions.
“Our long-term goal is to make men live as long as women and also women as healthy as men in late life. But for that, we need to understand where the differences come from”, explains Yu-Xuan Lu, one of the leading authors of the study.
Rapamycin extends lifespan only in female flies
The researchers gave the anti-aging drug rapamycin to male and female fruit flies to study the effect on the different sexes. Rapamycin is a cell growth inhibitor and immune regulator that is normally used in cancer therapy and after organ transplantations. They found that rapamycin extended the lifespan and slowed age-related intestinal pathologies in female flies but not in males.
Healthier life due to more autophagy
The researchers observed that rapamycin increased autophagy – the cell’s waste disposal process – in the female intestinal cells. Male intestinal cells, however, already seem to have a high basal autophagy activity, which cannot be further increased by rapamycin.
The scientists could also see this effect of rapamycin in mice. Female mice showed increased autophagy activity after treatment with rapamycin. “Previous studies found that females had greater responses to rapamycin on lifespan extension than did males in mice, we now uncover an underlying mechanism of these differences using flies”, says Yu-Xuan Lu.
Sex-specific, personalized treatments
“Sex can be a decisive factor for the effectiveness of anti-aging drugs. Understanding the processes that are sex-specific and determine response to therapeutics will improve the development of personalized treatments”, explains Linda Partridge, senior author of the study.
Reference: “Sexual identity of enterocytes regulates autophagy to determine intestinal health, lifespan and responses to rapamycin” by Jennifer C. Regan, Yu-Xuan Lu, Enric Ureña, Ralf L. Meilenbrock, James H. Catterson, Disna Kißler, Jenny Fröhlich, Emilie Funk and Linda Partridge, 1 December 2022, Nature Aging.