At Longevity Summit Dublin 2024, Joris Deelen from the Max Planck Institute for Biology of Ageing presented his research on the genetic basis of human longevity. His work highlights how rare genetic variants, particularly in key pathways like insulin signalling, may contribute to superlongevity. By introducing these human variants into mice, his team observed beneficial effects that could inform future interventions aimed at extending healthspan and lifespan in humans.

Key Points:

• Longevity and Genetics: Human longevity is partly heritable, and rare genetic variants may play a key role in determining why some individuals live exceptionally long lives.
• APOE Gene and Longevity: The APOE gene is consistently linked to longevity, with APOE2 being protective and APOE4 increasing risks of Alzheimer's and cardiovascular diseases. However, some long-lived individuals still carry APOE4, suggesting protective mechanisms.
• Healthspan vs. Lifespan: Longevity, healthspan, and lifespan are genetically correlated but involve different genetic components, with diseases like coronary artery disease and stroke inversely related to longevity.
• Rare Genetic Variants: Rare genetic variants in genes like FOXO3 are linked to human longevity, affecting ageing-related pathways such as the insulin-IGF-1 signalling pathway.
• Pathway-Based Research: Gene expression studies show that longevity-linked variants influence key pathways, including heme metabolism and insulin signalling, which play important roles in ageing.
• Functional Studies in Mice: Rare variants from long-lived humans were introduced into mice using gene editing. These variants showed promising results in improving traits like motor coordination, growth, and potentially extending lifespan, particularly in females.