Advanced maternal age impairs uterine decidualization through reduced RICTOR signaling, a protein kinase component involved in nutrient sensing. The RICTOR agonist MHY1485 restores decidual function in aged tissue, suggesting a molecular target for age-related pregnancy loss.
Key Points
- RICTOR protein significantly reduced in decidual tissue of women with advanced maternal age
- RICTOR activation via MHY1485 rescues decidualization defects in aged uterine models
- RICTOR regulates FoxO1 nuclear export; loss impairs Akt3-FoxO1 signaling pathway
Longevity Analysis
This research identifies a specific molecular mechanism linking aging to reproductive decline, establishing RICTOR as both a biomarker for uterine senescence and a therapeutic target. The pathway involves nutrient-sensing machinery and transcription factor regulation—systems that degrade with age across multiple tissues. Restoring this signaling offers a model for how age-related functional decline in specialized tissues might be reversed through targeted pathway reactivation, with implications extending beyond pregnancy to understanding how senescence compromises organ-specific regenerative capacity.
Original published by Wiley Aging Cell, by Yifeng Lin, Jiwei Sun, Yue Ying, Dan Li, Yuewen Ying, Xilin Shen, Xiao Sun, Dan Zhang, Yiqing Wu, Runju Zhang .