How African turquoise killifish press the pause button on aging

 African turquoise killifish embryos put organ development on hold during a state of suspended growth called diapause. Organs like the brain, eyes and ears (pictured in a developmentally suspended embryo) enter diapause with multiple cell types, such as precursor nerve cells (pink), glial cells (blue) and mature nerve cells (green).

CHI-KUO HU

The fish can double their life span by temporarily halting cell and organ growth while embryos

By Erin Garcia de Jesus

When the ponds where one African fish lives dry up, its offspring put their lives on pause. And now researchers have a sense for how the creatures do it.  

African turquoise killifish embryos can halt their development during a state of suspended activity called diapause. Now a study shows that the embryos effectively don’t age while in that state. Genetic analyses reveal that, to stay frozen in time, the embryos put functions such as cell growth and organ development on hold, researchers report in the Feb. 21 Science.

“Nature has identified ways to pause the clock,” says Anne Brunet, a geneticist Stanford University. Knowing how killifish pause their lives could help scientists figure out how to treat aging-related diseases or learn how to preserve human organs long-term, she says.

Nematode worm larvae (Caenorhabditis elegans) can also halt development and aging when faced with a lack of food or if their environment is overcrowded. Invertebrates like nematodes, however, lack many of the features that make other animals age, such as an adaptive immune system. More than 130 species of mammals from mice to bears also have some form of diapause.

The killifish (Nothobranchius furzeri) live in ponds in Mozambique and Zimbabwe that disappear for months during the dry season, leaving the fish without a home until the rain returns (SN: 8/6/18). For adults that typically live only four to six months anyway, vanishing ponds don’t pose much of a threat. But some killifish embryos press pause on their development during dry months, until ponds fill up again. 

Killifish advance from colorful, young fish to pale, old fish within a few months, making them a good animal for scientists to use to study aging.CHI-KUO HU

Killifish embryos can put their growth on hold from five months up to two years, matching or even greatly exceeding their typical adult life span. If humans could do something similar, an 80-year-old person might instead have a life span from 160 to more than 400 years, Brunet says. But if, or how, these animals protect themselves from aging while in this limbo was unknown.

In the study, Brunet and her colleagues compared killifish embryos that halted their growth with those that bypassed diapause and hatched into adults. Diapause didn’t decrease an adult fish’s growth, life span or ability to reproduce — a sign that the animal didn’t age, even if it paused its development for longer than its typical lifetime, the researchers found.

The team then analyzed the genetic blueprint of embryos suspended in diapause to determine which genes were active. Although the young killifish had developing muscles, hearts and brains before diapause, genes involved in organ development and cell proliferation were subsequently turned off. But other genes were cranked up, such as some crucial for turning other sets of genes on or off.

Killifish embryos (one pictured) can pause their development for a few months or up to two years during a state of suspended activity called diapause.CHI-KUO HU

One gene, the chromobox 7 gene, or CBX7, repressed genes involved in metabolism, but turned on those important for maintaining muscle and staying in diapause, the researchers found. Embryos without CBX7 came out of diapause sooner, and their muscles began to deteriorate after one month.

The new study shows that the embryos aren’t passively waiting for better environmental conditions — their cells coordinate responses during diapause that protect killifish from the passage of time. “We have always looked at this diapause state as more passive — nothing happens there,” says Christoph Englert, a molecular geneticist at the Leibniz Institute on Aging in Jena, Germany, who wasn’t involved in the work. But the new research “shifts the paradigm of diapause as a passive, boring state to an active state of embryonic nondevelopment.”

Researchers aren’t sure how things like temperature might spark a developing killifish to begin or end diapause. But understanding what’s going on inside an embryo is a step toward pinpointing how external signals might control when the animals suspend time, Englert says.      

CITATIONS

C.K. Hu et al. Vertebrate diapause preserves organisms long term through Polycomb complex members. Science. Vol 367, February 21, 2020, p. 870. doi:10.1126/science.aaw2601.

About Erin Garcia de Jesus

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Erin I. Garcia de Jesus is the Winter 2019 science writing intern at Science News. She holds a PhD in microbiology from the University of Washington and went on to earn a master’s in science communication from the University of California, Santa Cruz.

The Human Body Has Another Organ: The Mesentery

(Credit: J Calvin Coffey/D Peter O’Leary/Henry Vandyke Carter)

By Nathaniel Scharping

To the 78 organs that make up the human body, we can add one more: the mesentery.

Located in our abdominal cavity, the mesentery is a belt of tissue that holds our intestines in place. While anatomists knew it was there, it was always thought to be composed of several different segments, as opposed to being one single structure. This knocked it out of contention for organ status, as our bodily organs must be continuous, as well as provide some vital function to our anatomy.

A new study from researchers at the University Hospital Limerick reveals that the mesentery is actually one single band of tissue, beginning at the pancreas and continuing down through the small intestine and colon, wrapping around these vital organs to hold them tight and help them maintain their structure. It is made of a folded-over ribbon of peritoneum, a type of tissue usually found lining the abdominal cavity.

“Without it you can’t live,” says J. Calvin Coffey, a Limerick University Hospital researcher and colorectal surgeon. “There are no reported instances of a Homo sapien living without a mesentery.”

It was by peeling away the peritoneum and repeated observations that Coffey built his case for the mesentery. In 2012, Coffey’s team determined the mesentery was indeed a single, connected structure. In this most recent study, published in The Lancet, Coffey’s team outlines evidence collected over four years that affirms the mesentery’s organ status. The mesentery is highly integrated with the intestine, he says, and is located in an area of the human body that has not been fully explored — we still, apparently, contain new frontiers.

And, according to The Independent, the seminal medical textbook Gray’s Anatomy was updated in 2015 to include the new definition of the mesentery. However, Coffey isn’t exactly sure when an organ is officially an organ.

“That’s a fascinating question. I actually don’t know who the final arbiter of that is,” says Coffey.

In apes and other creatures that walk on all fours, he says that the structure of the mesentery, and the organs it supports, is slightly different, which affects the layout of their guts. Understanding how and why our digestive system is arranged the way it is could be crucial to our understanding of diseases like Crohn’s and irritable bowel syndrome.

“There are a lot of disease that we are stalled on, and we need to refresh our approach to these diseases,” Coffey says. “Now that we’ve clarified its structure, we can systematically examine it. We’re at a very exciting place right now.”

The era of mesenteric science has begun.