The precursor of PI(3,4,5)P3 alleviates aging by activating daf-18(Pten) and independent of daf-16.

Aging is characterized by the loss of homeostasis and the general decline of physiological functions, accompanied by various degenerative diseases and increased rates of mortality. Aging targeting small molecule screens have been performed many times, however, few have focused on endogenous metabolic intermediates-metabolites. Here, using C. elegans lifespan assays, we conducted a worm metabolite screen and identified an eukaryotes conserved metabolite, myo-inositol (MI), to extend lifespan, increase mobility and reduce fat content. Genetic analysis of enzymes in MI metabolic pathway suggest that MI alleviates aging through its derivative PI(4,5)P2. MI and PI(4,5)P2 are precursors of PI(3,4,5)P3, which is negatively related to longevity. The longevity effect of MI is dependent on the tumor suppressor gene, daf-18 (homologous to mouse Pten), independent of its classical pathway downstream genes, akt or daf-16. Furthermore, we found MI effects on aging and lifespan act through mitophagy regulator PTEN induced kinase-1 (pink-1) and mitophagy. MI's anti-aging effect is also conserved in mouse, indicating a conserved mechanism in mammals.

The Study of Low Calcium Dialysate on Elderly Hemodialysis Patients with Secondary Hypoparathyroidism.

OBJECTIVE: The study aimed to study the safety and efficacy of 1.25 mmol/l calcium dialysate on maintenance hemodialysis (MHD) in elderly patients who suffered from secondary hypoparathyroidism. METHODS: Eighty-two elderly patients (ages ≥65) who had been in MHD with dialysate calcium at 1.5 mmol/l over 6 months and had 2 consecutive serum intact parathyroid hormone (iPTH) measurements at level below 100 pg/ml were selected and randomized into 2 groups: treatment group (41 patients, with dialysate calcium at 1.25 mmol/l) and control group (41 patients, still with dialysate calcium at 1.5 mmol/l). Both groups were studied for the duration of 12 months. The changes of serum iPTH, calcium, phosphorus, calcium and phosphorus product and other indicators as well as related adverse reactions were recorded at the following time points: before the study and 1, 3, 6 and 12 months into the study. In addition, the intimal media thickness (IMT) of carotid artery and abdominal aorta calcification score (AACS) were measured in the 0, 6 and 12 months during the study. RESULTS: (1) In the treatment group, the levels of serum corrected calcium, phosphorus and calcium-phosphate product began to decline after 1 month and exhibited further decrease 3 months later. Serum iPTH level increased significantly after 1 month into the study and the trend continued. The above markers stabilized after month 6. Compared with pre-study markers, the changes of the above markers were significant after study (p < 0.05). (2) The average IMT and AACS were evidently decreased during the 6 and 12 months of study in the treatment group. There was statistical significance (p < 0.05) when compared with the above indexes of the pre-study and the control group. (3) In the control group, there were no significant differences in above laboratory markers over the 12-month study period. (4) There was no significant difference in the adverse events observed between the 2 groups. CONCLUSION: Safety of low calcium dialysate (dialysate calcium 1.25 mmol/l) in elderly MHD patients with iPTH <100 pg/ml is good, as well as improving carotid IMT, resistance index and AACS as indexes of vascular calcification in the small study group and warrants further investigation.