Lessons on Human Longevity … From Rockfish

Multi-species analyses reveal shared genes linked to longer life span

red and white fish with open mouth in a fish tank
Analyses of rockfish such as Sebastes miniatus helped researchers home in on genes associated with longevity in humans. Video: CrackerClips/Creatas Video+/Getty Images Plus

A team led by scientists at Harvard Medical School and Boston Children’s Hospital has found a new biological pathway linked to longer life span in humans — thanks to a study in fish.

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It helps when a postdoctoral fellow interested in aging works in the lab of a self-professed “fish guy” who specializes in unearthing clues about organismal evolution and development in piscine genomes.

The postdoc in question, Stephen Treaster, HMS research fellow in genetics in the lab of Matthew Harris, analyzed the DNA of 23 species of rockfish — a diverse clade of fish that hide among rocks on seafloors around the world.

Rockfish offer a unique opportunity to study longevity because they include more than 100 species that have evolved to exhibit a vast range of life spans, from 11 years to more than 200 years.

The fish exhibit other characteristics that appeal to geneticists: They evolved and diverged recently and, unlike many other animals, show little or no apparent link between their life span and their body size or the environments in which they live.

Treaster and colleagues reported Jan. 11 in Science Advances that comparing the species’ DNA revealed a set of genes associated with changes in their life spans.

Some of those genes were already known to regulate longevity in humans and many other species, including genes that produce proteins involved in insulin signaling, glycogen regulators, sirtuins, and amyloid precursors whose abnormal processing contributes to Alzheimer’s disease.

But other genes hadn’t been flagged before. Among the surprise candidates were genes involved in flavonoid metabolism. Despite the name, these genes normally regulate steroid hormones that affect how long an organism takes to reach sexual maturation.

To determine whether the findings pertained to people or were relevant only to fish, the team combed through a database of human genome sequences.

They found that the same flavonoid metabolism genes underlying longevity in rockfish had unique variations in human participants who lived extraordinarily long lives.

The findings suggest that flavonoid metabolism can be added to the collection of biological pathways that influence human longevity. The link, however, needs to be explored further before scientists can say for certain whether these genes affect life span and, if so, exactly how. Treaster and colleagues are now trying to answer those questions in zebrafish models.

  • In depth

    Why would an organism evolve to die earlier? And what does that have to do with flavonoid metabolism? 

    Previous research had indicated that ancient rockfish had short life spans and that some species then evolved to live longer. Harris’ team, however, found the opposite. Their analyses showed that rockfish’s common ancestors were long-lived, meaning that some species developed shorter life spans over the millennia. 

    Treaster suspects that threats to the lives of certain rockfish species — such as new predators, disease, and climate change — have driven changes in flavonoid metabolism genes in those species. The shift in steroid hormone levels allows them to start making baby rockfish at a younger age and ensure the continuation of the species, but with the trade-off of a shorter life span. 

    “The selection pressures may mean you need to reproduce faster before something eats you or you get sick,” he said.