These African Turquoise Killifish “Press Pause” on Aging

Genetic analyses show that to stay frozen in time, the embryos slow cell growth and organ development, according to the new Science Magazine report.

“Nature has identified ways to pause the clock,” said Anne Brunet, a geneticist at Stanford University, to Science. She added that knowing how killifish freeze their biological lives could help scientists understand how they might one day treat aging-related diseases, or learn how to preserve human organs in the long-term.

Nematode worm larvae (Caenorhabditis elegans) are also capable of pausing development and aging when faced with a lack of food, or an overcrowded environment. Nematodes — which are invertebrates — lack many usual features that make other creatures age, like an adaptive immune system. More than 130 mammals, including mice and bears, also possess some diapause capability.

How killifish extend their lifespan

Killifish (Nothobranchius furzeri) live in ponds of Mozambique and Zimbabwe that vanish for months throughout the dry season, which leaves fish without a viable home, until rain returns. Adults live only four to six months, so seasonal pond disappearances don’t pose a significant threat to their short lives. However, some killifish embryos halt their development, so their lifespans may last until the pond refills again.

Killifish embryos can pause their growth from five months to two years, longer than most adults of the species normally live. If humans could do the same, an 80-year-old person might have a total lifespan from 160 to more than 400 years, said Brunet, to Science.

In the study, Brunet and her colleagues compared normally-aging killifish with those whose aging was halted in the embryonic stage. They found that diapause didn’t decrease an adult fish’s growth, ability to reproduce, or lifespan — which means the animal didn’t age, despite pausing in development for a longer period than its normal lifespan.

The specific genes turned off during diapause were those involved in cell proliferation and organ development. Others were cranked up — especially the ones needed for turning other sets of genes off.

However, the killifish embryos aren’t passively waiting for improved environmental conditions — their cells coordinate to respond in unison during diapause. This protects killifish from the passage of time. “We have always looked at this diapause state as more passive — nothing happens there,” said Christoph Englert, a molecular geneticist in Germany, who wasn’t involved in the study, to Science. However, he also said that the new study “shifts the paradigm of diapause as a passive, boring state to an active state of embryonic nondevelopment.”

Varying temperatures may change the way developing killifish begin or end diapause, but the ongoing study of what happens in embryos is a step toward coming to know how external stimuli influence when animals pause their aging process, according to Englert.