Editors' ChoiceFertility

Rapamycin keeps the reproductive clock ticking

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Science Translational Medicine  31 May 2017:
Vol. 9, Issue 392, eaan4296
DOI: 10.1126/scitranslmed.aan4296

Abstract

Two weeks of rapamycin administration in young and old female mice leads to long-term improvements in ovarian function and reproductive longevity.

Aging is associated with physiological, structural, and functional declines in many cellular and tissue processes. In women, one of the first and most rapid of these declines is in ovarian health and reproductive capacity. Not only is the potential for childbearing diminished with age, but so are the cardiovascular, metabolic, and hormonal benefits associated with the premenopausal state. Current interventions for extending life span and delaying aging in model organisms, such as long-term dietary restriction or treatment with the drug rapamycin, can have negative consequences on estrous cycles and reproductive output. However, short-term use or timed applications of longevity-extending methods have not been thoroughly investigated as a means to improve reproductive longevity and ovarian health in humans or mammalian models.

Dou et al. demonstrated that short-term rapamycin treatment given for 2 weeks in 8-week-old mice (equivalent to 20 to 30 years of age in humans) or 8-month-old mice (equivalent to 38 to 47 years in humans) is effective at extending the healthy functional capacity of female ovaries and allowing for increased reproductive capacity in later life. Although rapamycin treatment resulted in mild short-lived disturbances in ovarian function for up to 2 months after treatment, in the long term it preserved primordial follicles, enhanced the microenvironment of the ovaries, improved the quality and yield of oocytes, and increased the number of pups born for up to 16 months in both young and old treatment groups. On a molecular level, the transient rapamycin treatment stimulated anti-aging sirtuin gene expression in the ovaries of both young and older mice.

These findings support a potential short-term intervention that increases maximum childbearing age and, although not tested in this study, a possible method to extend the cardiovascular protection afforded by healthy and functioning ovaries. While additional rodent and human testing will be needed to ensure the safety and efficacy of this method, the extension of ovarian life span without negative effects on reproductive function poses a therapeutic goal for healthy aging in women.

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