Female germline stem cells: aging and anti-aging

Abstract

The delay of ovarian aging and the fertility preservation of cancer patients are the eternal themes in the field of reproductive medicine. Acting as the pacemaker of female physiological aging, ovary is also considered as the principle player of cancer, cardiovascular diseases, cerebrovascular diseases, neurodegenerative diseases and etc. However, its aging mechanism and preventive measures are still unclear. Some researchers attempt to activate endogenous ovarian female germline stem cells (FGSCs) to restore ovarian function, as the most promising approach. FGSCs are stem cells in the adult ovaries that can be infinitely self-renewing and have the potential of committed differention. This review aims to elucidate FGSCs aging mechanism from multiple perspectives such as niches, immune disorder, chronic inflammation and oxidative stress. Therefore, the rebuilding nichs of FGSCs, regulation of immune dysfunction, anti-inflammation and oxidative stress remission are expected to restore or replenish FGSCs, ultimately to delay ovarian aging.

Keywords: Aging related mechanisms; Anti-aging strategies; Female germline stem cells; Ovarian aging; Stem cell aging.

Fig.1

Hypoxia-induced chronic inflammation and oxidative stress on stem cell senescence. Hypoxia promotes the generation of inflammatory factors such as TNF-α, IFN7 and IL-6 through hypoxia-inducible factor-1 alpha (HIF-1 α), leading to chronic ovarian inflammation, and also induces excessive production of ROS, leading to the formation of DNA adducts such as 8-OXo-7, 8-dihydro-2'-deoxyguanine and 4-hydroxynonenal. Together with inflammatory factors, these two substances cause accumulation of damage to DNA, changes in epigenetics, abnormalities in gene expression, dysregulation of cellular signaling pathways, etc., ultimately leading to aging of cells and organs