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  • Perspective
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Emerging therapeutic strategies to mitigate female and male reproductive aging

Nature Aging volume 4, pages 1682–1696 (2024)Cite this article

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Abstract

People today are choosing to have children later in life, often in their thirties and forties, when their fertility is in decline. We sought to identify and compile effective methods for improving either male or female fertility in this context of advanced reproductive age. We found few clinical studies with strong evidence for therapeutics that mitigate reproductive aging or extend fertility; however, this Perspective summarizes the range of emerging experimental strategies under development. Preclinical studies, in mouse models of aging, have identified pharmaceutical candidates that improve egg and sperm quality. Further, a diverse array of medically assisted reproduction methodologies, including those that stimulate rare ovarian follicles and rejuvenate egg quality using mitochondria, may have future utility for older patients. Finally, we highlight the many knowledge gaps and possible future directions in the field of therapeutics to extend the age of healthy human reproduction.

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Fig. 1: Summary of emerging therapeutic strategies to mitigate female reproductive aging.
Fig. 2: Summary of emerging therapeutic strategies to mitigate male reproductive aging.

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Acknowledgements

We acknowledge the many researchers whose primary works on the mechanisms of reproductive aging could not be included due to space constraints and restrictions on the number of references.

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Author notes

  1. These authors contributed equally: Yasmyn E. Winstanley, Jennifer S. Stables.

Authors and Affiliations

  1. Robinson Research Institute, School of Biomedicine; The University of Adelaide, Adelaide, South Australia, Australia

    Yasmyn E. Winstanley, Jennifer S. Stables, Macarena B. Gonzalez & Rebecca L. Robker

  2. Graduate School of Integrated Sciences for Life, Hiroshima University, Higashi-Hiroshima, Japan

    Takashi Umehara

  3. Robinson Research Institute, Adelaide Medical School; The University of Adelaide, Adelaide, South Australia, Australia

    Robert J. Norman

Authors
  1. Yasmyn E. Winstanley
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  2. Jennifer S. Stables
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  4. Takashi Umehara
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  6. Rebecca L. Robker
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Contributions

T.U., Y.E.W., J.S.S., M.B.G. and R.L.R. reviewed the literature and compiled the studies to be included. Y.E.W. and J.S.S. wrote the sections about female reproductive aging. M.B.G. wrote the sections about male reproductive aging. R.J.N. provided clinical expertise and critical review. R.L.R. wrote the conclusions section with input from all authors. Y.E.W. prepared the figures with input from all authors. J.S.S. compiled the tables with input from all authors. All authors reviewed multiple drafts of the manuscript. R.L.R. supervised and coordinated all aspects of the literature review and manuscript preparation.

Corresponding author

Correspondence to Rebecca L. Robker.

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Competing interests

M.B.G. and R.L.R. are inventors on a patent related to the actions of BGP-15 to improve gamete quality filed by The University of Adelaide and owned by Mitochon Technologies. R.L.R. is a consultant for Vitaleon Pharma. The other authors declare no competing interests.

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Nature Aging thanks Shweta Dipali, Zhi Zhou, Bo Xiong, and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Winstanley, Y.E., Stables, J.S., Gonzalez, M.B. et al. Emerging therapeutic strategies to mitigate female and male reproductive aging. Nat Aging 4, 1682–1696 (2024). https://doi.org/10.1038/s43587-024-00771-4

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