Mitochondria: the epigenetic regulators of ovarian aging and longevity

Front Endocrinol (Lausanne). 2024 Nov 13:15:1424826. doi: 10.3389/fendo.2024.1424826. eCollection 2024.

Abstract

Ovarian aging is a major health concern for women. Ovarian aging is associated with reduced health span and longevity. Mitochondrial dysfunction is one of the hallmarks of ovarian aging. In addition to providing oocytes with optimal energy, the mitochondria provide a co-substrate that drives epigenetic processes. Studies show epigenetic alterations, both nuclear and mitochondrial contribute to ovarian aging. Both, nuclear and mitochondrial genomes cross-talk with each other, resulting in two ways orchestrated anterograde and retrograde response that involves epigenetic changes in nuclear and mitochondrial compartments. Epigenetic alterations causing changes in metabolism impact ovarian function. Key mitochondrial co-substrate includes acetyl CoA, NAD+, ATP, and α-KG. Thus, enhancing mitochondrial function in aging ovaries may preserve ovarian function and can lead to ovarian longevity and reproductive and better health outcomes in women. This article describes the role of mitochondria-led epigenetics involved in ovarian aging and discusses strategies to restore epigenetic reprogramming in oocytes by preserving, protecting, or promoting mitochondrial function.

Keywords: aging; epigenetics; menopause; mitochondria; ovary.

Publication types

  • Review

MeSH terms

  • Aging* / genetics
  • Aging* / physiology
  • Animals
  • Epigenesis, Genetic*
  • Female
  • Humans
  • Longevity* / genetics
  • Mitochondria* / genetics
  • Mitochondria* / metabolism
  • Oocytes / metabolism
  • Ovary* / metabolism
  • Ovary* / physiology

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. SM, VS, CS, and AK are supported by institutional funds. KS research is supported by NIH grant 5R21OD031970, funding from Nathan Shock Center for Biology of Aging, University of Alabama at Birmingham and Breast Cancer Foundation of Alabama.