An expanding GSK3 network: implications for aging research

The last few decades of longevity research have been very exciting. We now know that longevity and healthspan can be manipulated across species, from unicellular eukaryotes to nonhuman primates, and that while aging itself is inevitable, how we age is malleable. Numerous dietary, genetic, and pharmacological studies now point to links between metabolism and growth regulation as a central aspect in determining longevity and, perhaps more importantly, health with advancing age. Here, we focus on a relatively new player in aging studies GSK3, glycogen synthase kinase, a key factor in growth and metabolism whose name fails to convey the extensive breadth of its role in cellular adaptation. First, we provide a brief overview of GSK3, touching on those aspects that are likely relevant to aging. Then, we outline the role of GSK3 in cellular functions including growth signaling, cell fate, and metabolism. Next, we describe evidence demonstrating a direct role for GSK3 in a range of age-related diseases, despite the fact that they differ considerably in their etiology and pathology. Finally, we discuss the role that GSK3 may play in normative aging and how GSK3 might be a suitable target to oppose age-related disease vulnerability.