The killifish is an emerging model for investigating the genetic architecture of aging and age-related pathologies, which often exhibit sex-specific patterns between females (left) and males (right). Credit: Itamar Harel
A new study provides experimental evidence for the theory of antagonistic pleiotropy: the idea that certain genes can provide advantages early in life while contributing to disease and decline in old age. While widely accepted in theory, scientists have struggled to identify specific genes responsible for such trade-offs in vertebrates.
Using the African turquoise killifish—a short-lived species recently pioneered by Professsory Itamar Harel at Hebrew University and colleagues for genetic aging research—the team focused on the gene vgll3, which has been previously linked to the timing of human puberty and maturation in other species, particularly Atlantic salmon.
Modifying this gene using CRISPR caused the fish with altered vgll3 to grow faster and reach sexual maturity earlier, traits that could offer a reproductive advantage in natural environments. However, these benefits came with significant long-term costs. The same fish showed reduced lifespans and a higher incidence of age-related tumors, including melanoma-like cancers.
“We have effectively caught evolution in the act of making a trade-off. For years, we’ve asked why our bodies can’t just maintain themselves indefinitely. This gene gives us a direct answer: nature doesn’t prioritize longevity; it prioritizes continuity. We are built to sprint, not to marathon,” said Harel.
Further analysis showed that the gene influences key biological processes, including cell division, stem cell activity, and DNA repair. Increased cellular activity may help explain both the rapid development observed in younger fish and the accumulation of damage that leads to disease in older individuals.
Because vgll3 is conserved in humans, the findings may have broader implications for understanding human development, aging and age-related diseases. While previous association studies have linked the gene to puberty timing and hormone levels, functional data were missing until now.
Researchers say the next step will be to explore whether it is possible to separate the gene’s beneficial early-life effects from its harmful consequences later in life.
Data from The Hebrew University of Jerusalem