Aging and phosphoinositide remodeling

Aging affects diverse biological processes and increases the risk of disease. The plasma-membrane phospholipids known as phosphoinositides comprise hundreds of molecular species, and their composition (the phosphoinositide profile) is thought to provide a molecular basis for the robustness and resilience of living systems. Here we introduce our AMED-CREST project, “Age-related remodeling of phosphoinositides and the essence of aging and disease.”

Using our originally developed phosphoinositide-measurement technology (the PRMC-MS method), we found that the abundance of various phosphoinositide species in cultured cells and mouse tissues changes with age, remodeling the phosphoinositide profile. Using genetic, biochemical, and pharmacological approaches, we aim to identify aging-regulating phosphoinositide-metabolizing enzymes, to elucidate aging-regulating phosphoinositide profiles, and to control aging and age-related disease by intervening in phosphoinositide metabolism — thereby revealing how phosphoinositide metabolism contributes to fundamental aging.