PLX139710

GSE154417: The precursor of PI(3,4,5)P3 alleviates aging by activating daf-18(Pten) and independent of daf-16

• Organsim mouse
• Type RNASEQ
• Target gene
• Project ARCHS4

Aging is characterized by the loss of homeostasis and the general decline of physiological functions, accompanied by various degenerative diseases and higher rates of mortality. Anti-aging targeted small molecule screens have been carried outperformed many times, however, few have focused on endogenous metabolic intermediatesmetabolites. Here, using C. elegans lifespan assays, we conducted a worm metabolite screen and identified an conserved metabolite through eEukaryotes-conserved metabolite, myo-inositol (MI), to extend lifespan, increase mobility and reduce fat content. Genetic analysis of enzymes in MI metabolic pathway suggestsed 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. However, the mechanism study shows itslongevity effects could be fully blocked by a null-allele mutation of the tumor suppressor gene, daf-18 (homologous to mouse Pten), areand was independent of its classical pathway downstream elements, akt or daf-16., but Instead, we found MI effects on aging were dependent on its downstream mitophagy regulator pink-1. MIs anti-aging effect is was also conserved in mouse model, implicatingindicating a conserved mechanism in mammals that may extend to human. SOURCE: Xian Xia PICB, CAS