Environmental toxicants have been linked to aging and age-related diseases. The emerging evidence has shown that the enhancement of detoxification gene expression is a common transcriptome marker of long-lived mice, Drosophila melanogaster, and Caenorhabditis elegans. Meanwhile, the resistance to toxicants was increased in long-lived animals. Here, we show that farnesoid X receptor (FXR) agonist obeticholic acid (OCA), a marketed drug for the treatment of cholestasis, may extend the lifespan and healthspan both in C. elegans and chemical-induced early senescent mice. Furthermore, OCA increased the resistance of worms to toxicants and activated the expression of detoxification genes in both mice and C. elegans. The longevity effects of OCA were attenuated in Fxr ^-/- mice and Fxr homologous nhr-8 and daf-12 mutant C. elegans. In addition, metabolome analysis revealed that OCA increased the endogenous agonist levels of the pregnane X receptor (PXR), a major nuclear receptor for detoxification regulation, in the liver of mice. Together, our findings suggest that OCA has the potential to lengthen lifespan and healthspan by activating nuclear receptor-mediated detoxification functions, thus, targeting FXR may offer to promote longevity.

Objective:To evaluate the changes of mTOR signaling molecules in granulosa cells from polycystic ovary syndrome (PCOS) patients, and whether the change of mTOR siganaling is related to serum hormones.Methods:The phosphorylation levels of mTOR signaling molecules in primary granulosa cells were compared between PCOS group and control group. The correlation between phosphorylation levels of mTOR signaling and serum hormones was also analyzed. Then effects of exogenous testosterone and insulin on mTOR signaling were investigated in vitro. Results:Granulosa cells from PCOS patients (0.66±0.29) had higher phosphorylation levels of mTOR compared with control group (0.34±0.32, P=0.02). The level of p-s6k1 in PCOS group (0.95±0.42) was higher than that in control group (0.62±0.29), but the difference was not statistically significant ( P>0.05). The serum testosterone was associated with p-mTOR and p-S6k1 ( P=0.01, P=0.01). Serum follicle-stimulating hormone (FSH) ( P=0.67, P=0.75) and luteinizing hormone (LH) ( P=0.75, P=0.37) levels were irrelevant with p-mTOR and p-S6k1. Conclusion:Granulosa cells from PCOS patients had higher activated mTOR signaling. Testosterone and insulin could elevate the phosphorylation levels of mTOR signaling of granulosa cells in vitro, which maybe contributed to the dysfunction of granulosa cells and follicular development stagnation of PCOS.

Objective:To evaluate the changes of mTOR signaling molecules in granulosa cells from polycystic ovary syndrome (PCOS) patients, and whether the change of mTOR siganaling is related to serum hormones.Methods:The phosphorylation levels of mTOR signaling molecules in primary granulosa cells were compared between PCOS group and control group. The correlation between phosphorylation levels of mTOR signaling and serum hormones was also analyzed. Then effects of exogenous testosterone and insulin on mTOR signaling were investigated in vitro. Results:Granulosa cells from PCOS patients (0.66±0.29) had higher phosphorylation levels of mTOR compared with control group (0.34±0.32, P=0.02). The level of p-s6k1 in PCOS group (0.95±0.42) was higher than that in control group (0.62±0.29), but the difference was not statistically significant ( P>0.05). The serum testosterone was associated with p-mTOR and p-S6k1 ( P=0.01, P=0.01). Serum follicle-stimulating hormone (FSH) ( P=0.67, P=0.75) and luteinizing hormone (LH) ( P=0.75, P=0.37) levels were irrelevant with p-mTOR and p-S6k1. Conclusion:Granulosa cells from PCOS patients had higher activated mTOR signaling. Testosterone and insulin could elevate the phosphorylation levels of mTOR signaling of granulosa cells in vitro, which maybe contributed to the dysfunction of granulosa cells and follicular development stagnation of PCOS.

Educational reform of pathophysiology oriented to clinical application is to pass the physician qualifica -tion examination .One of essential approach is to implement pathophysiology teaching with the translational medical philosophy and promote the harmonious development of physician -patient relationship with the utilization of the de-velopment and changes of disease in the teaching process .In that way, the pathophysiology in basic and clinical medicine is worthy of the name of “bridge”, and ultimately achieves the goal of “the transformation and develop-ment of the cultivation of clinical application talents”.