Review-Key Symposium

The current increase in lifespan without an equivalent increase in healthspan poses a grave challenge to the healthcare system and society. Some individuals live long and healthy lives without major chronic diseases, and part of this trait is embedded in their genome. This review discusses findings from studies on the genetic component of human longevity and the main challenges of these studies. It then highlights results from genetic studies in model organisms and comparative genomics to identify conserved longevity-associated pathways. Synthesizing evidence across approaches, only five main pathways have been consistently linked to longevity: (1) insulin/insulin-like growth factor 1 signalling, (2) DNA-damage response and repair, (3) immune function, (4) cholesterol metabolism and (5) telomere maintenance. Given limitations of current human approaches, the authors propose future human longevity genetics should prioritize identification and functional characterization of rare genetic variants in genes within these pathways.

Larissa Smulders, Joris Deelen