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Unraveling female reproductive senescence to enhance healthy longevity

Cell Research volume 33, pages 11–29 (2023)Cite this article

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Abstract

In a society where women often want successful careers and equal opportunities to men, the early nature of ovarian aging often forces women to make difficult life choices between career and family development. Fertility in women begins to decline after the age of 37 years and it is rare for pregnancies to occur after 45. This reproductive decline in women is inevitable and culminates in menopause, which is a major driver of age-related diseases. In a world where biomedical advances are leading to modifiable biological outcomes, it is time to focus on mitigating female reproductive senescence to maintain fertility and preserve age-related hormonal functions, with the goal of providing increased life choices and enhancing healthspan. To date, reproductive longevity research remains an understudied field. More needs to be done to unravel the biology of the ovarian follicles, which are the functional units of reproductive lifespan and are comprised of cell types including the oocyte (female gamete) and a group of specialized supporting somatic cells. Biological attempts to maintain the quality and quantity of follicles in animal models through manipulating pathways involved in aging can potentially prolong female reproductive lifespan and healthspan. Here, we summarize the molecular events driving ovarian aging and menopause and the interventional strategies to offset these events. Developing solutions to female reproductive senescence will open doors to discover ways to enhance true healthy longevity for both men and women.

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Fig. 1: Ovarian follicles: the functional units of ovary for reproductive lifespan.
Fig. 2: Post-reproductive lifespan across species.36
Fig. 3: The post-reproductive lifespan is a result of a hypoestrogenic environment that has pleiotropic health effects.

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Acknowledgements

L.D. is funded for her PhD studies by National University of Singapore. The authors acknowledge the generous contribution of the Bia-Echo Foundation to Yong Loo Lin School of Medicine, National University of Singapore in the set-up of NUS Bia-Echo Asia Centre of Reproductive Longevity and Equality to change the science and narrative of female reproductive longevity.

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Author notes

  1. These authors contributed equally: Lu Dong, Daniel Boon Loong Teh.

Authors and Affiliations

  1. Integrative Sciences and Engineering Programme, NUS Graduate School, National University of Singapore, Singapore, Singapore

    Lu Dong & Brian Keith Kennedy

  2. NUS Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    Lu Dong & Brian Keith Kennedy

  3. Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    Daniel Boon Loong Teh & Brian Keith Kennedy

  4. NUS Bia Echo Asia Centre for Reproductive Longevity and Equality, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    Daniel Boon Loong Teh, Brian Keith Kennedy & Zhongwei Huang

  5. Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    Brian Keith Kennedy & Zhongwei Huang

  6. Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    Zhongwei Huang

  7. Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore

    Zhongwei Huang

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Contributions

Z.H. and B.K.K. conceptualized and led the review. D.B.L.T. and L.D. performed the literature review, summarized data, constructed the figures and wrote the first version of the manuscript. B.K.K. and Z.H. revised and critically reviewed the subsequent draft revisions. All authors read, edited, and approved the final article.

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Correspondence to Brian Keith Kennedy or Zhongwei Huang.

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Dong, L., Teh, D.B.L., Kennedy, B.K. et al. Unraveling female reproductive senescence to enhance healthy longevity. Cell Res 33, 11–29 (2023). https://doi.org/10.1038/s41422-022-00718-7

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