Researchers have identified a gene that directly links early-life growth and reproductive success with accelerated ageing and increased cancer risk later in life, offering new insight into a longstanding theory in evolutionary biology.
Now, an international team of researchers 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.
What’s fascinating – and slightly terrifying – is that the cancer we see in these fish isn’t a random accident. It’s the direct shadow of their youthful vitality
Prof Itamar Harel
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 Harel and colleagues for genetic ageing 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.
By modifying this gene using CRISPR technology, the researchers observed clear effects. Fish with altered vgll3 grew faster and reached 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 tumours, 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 prioritise longevity; it prioritises continuity. We are built to sprint, not to marathon,” said Prof Itamar Harel at Hebrew University.
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.
The researchers also developed a new immunodeficient killifish model, enabling them to transplant and study tumour cells in ways not previously possible in this system.
“What’s fascinating – and slightly terrifying – is that the cancer we see in these fish isn’t a random accident. It’s the direct shadow of their youthful vitality. The same machinery that drives a cell to build a young body is hijacking the system to build a tumour in the old one. If we can understand this mechanism, we might finally learn how to decouple healthy growth from the disease of ageing,” Dr Harel added.
Because vgll3 is conserved in humans, the findings may have broader implications for understanding human development, ageing, and age-related diseases. While previous association studies have linked the gene to puberty timing and hormone levels, functional data were missing until now.
The discovery could contribute to future efforts in cancer prevention and research aimed at extending healthy lifespan. 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.
Source: EurekAlert!
