Researchers at Leiden University have identified a rare gene variant that could protect against age-related diseases, based on a study involving over 200 long-lived families. The findings were presented at the annual meeting of the European Society of Human Genetics in Gothenburg.
Pasquale Putter's team analyzed the genomes of 212 sibling groups from the "Leiden Longevity Study" and identified twelve rare variants associated with exceptionally long and healthy lives. Particularly striking was a mutation in the CGAS gene (cyclic GMP-AMP synthase), which appeared in two families.
CGAS is a sensor of the innate immune system that triggers inflammatory responses when damaged or foreign DNA is detected within the cell. The discovered variant means that affected individuals possess only one active copy of the gene instead of two. This reduces chronic, low-grade inflammatory activity—known as "inflammaging"—while maintaining immune defense against infections.
Previous research had already shown that offspring of long-lived parents develop cardiovascular diseases, on average, 13 years later than their peers. The new study now provides a molecular explanation for this phenomenon. As a next step, the researchers plan to test the CGAS mutation in killifish—the shortest-lived vertebrates—to measure its effect on lifespan and tissue health.
Source: European Society of Human Genetics, Annual Meeting Gothenburg, June 21, 2026; presented by Pasquale Putter, Leiden University Medical Center.
