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Extension of longevity and reduction of inflammation is ovarian-dependent, but germ cell-independent in post-reproductive female mice

Abstract

Cardiovascular disease, rare in premenopausal women, increases sharply at menopause and is typically accompanied by chronic inflammation. Previous work in our laboratory demonstrated that replacing senescent ovaries in post-reproductive mice with young, actively cycling ovaries restored many health benefits, including decreased cardiomyopathy and restoration of immune function. Our objective here was to determine if depletion of germ cells from young transplanted ovaries would alter the ovarian-dependent extension of life and health span. Sixty-day-old germ cell-depleted and germ cell-containing ovaries were transplanted to post-reproductive, 17-month-old mice. Mean life span for female CBA/J mice is approximately 644 days. Mice that received germ cell-containing ovaries lived 798 days (maximum = 815 days). Mice that received germ cell-depleted ovaries lived 880 days (maximum = 1046 days), 29% further past the time of surgery than mice that received germ cell-containing ovaries. The severity of inflammation was reduced in all mice that received young ovaries, whether germ cell-containing or germ cell-depleted. Aging-associated inflammatory cytokine changes were reversed in post-reproductive mice by 4 months of new-ovary exposure. In summary, germ cell depletion enhanced the longevity-extending effects of the young, transplanted ovaries and, as with germ cell-containing ovaries, decreased the severity of inflammation, but did so independent of germ cells. Based on these observations, we propose that gonadal somatic cells are programed to preserve the somatic health of the organism with the intent of facilitating future germline transmission. As reproductive potential decreases or is lost, the incentive to preserve the somatic health of the organism is lost as well.

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Acknowledgments

The authors thank Dr. Aaron Olsen and Ms. Lisa DeSoi for help with the mice, Dr. Erik Eide and Mr. Mahdi Nazokkarmaher for help with VCD injections, and Ms. Sumira Phatak for guidance with magnetic resonance imaging. The authors also thank Dr. Shelley Cargill and Dr. Chris Pearl for critical review of the manuscript. Research reported in this publication was supported by Utah State University, School of Veterinary Medicine, Department of Animal, Dairy and Veterinary Sciences Research Initiation Funds, the Cluster of Excellence for Aging Research (CECAD) at the University of Cologne and by a generous gift of aged CBA/J female mice from Nancy Nadon at the National Institute on Aging.

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Conceived and designed the experiments: TH, JM. Performed the experiments: TH, KP, GH, YI, JE, BS, JM. Analyzed the data: TH, GH, YI, JE, BS, JM. Contributed reagents/materials/analysis tools: YI, BS, JM. Wrote the paper: TH, KP, JM.

Corresponding author

Correspondence to Jeffrey B. Mason.

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The authors declare that they have no conflicts of interest.

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Habermehl, T.L., Parkinson, K.C., Hubbard, G.B. et al. Extension of longevity and reduction of inflammation is ovarian-dependent, but germ cell-independent in post-reproductive female mice. GeroScience 41, 25–38 (2019). https://doi.org/10.1007/s11357-018-0049-4

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  • DOI: https://doi.org/10.1007/s11357-018-0049-4

Keywords

  • Ovarian
  • Menopause
  • Inflammation
  • Life span
  • Germ cell
  • Aging