Prioritizing Progeny: Germline stem cells go dormant during starvation

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Duke researchers are gaining a better understanding of how nutrient deprivation affects development. Using roundworms, Ryan Baugh, PhD, associate professor of biology, and team investigated gene regulation during larval starvation. Their findings, published in Cell Reports on October 11, have implications for aging across species, including humans.

Previous studies have looked at gene regulation in starved roundworms hours after they have hatched without food, but Baugh dug deeper, looking at effects over longer periods of time, up to 12 days after hatching, as the worms approach death.

By investigating several time points over those 12 days and using RNA sequencing, Baugh and his team created an atlas of gene expression, and they discovered that out of the 558 cells in the roundworm, mRNA remains stable only in the two germline cells, while it slowly degrades in all other cells. Germline cells contain the genetic information passed down from one generation to the next.

“This mechanism of maintaining transcriptional quiescence and stabilizing the transcriptome of the germ cells,” Baugh said, “appears to be an important strategy to maintaining reproductive success following starvation.” In other words, all other cells actively mount a starvation response, but germline cells go dormant, which could help them reproduce later if the worm finds food.

When food becomes available, development doesn’t immediately kick in. There’s a lag phase proportional to the duration of starvation, but when development does resume, it’s fairly normal. “If they’ve been starved for a long time, though, then there is a lot of variation in the population,” Baugh noted. Worms that have been starved for a week or more tend to be smaller on average and produce fewer progeny, and those progeny are of lower quality.

Roundworms only have a lifespan of about 2-3 weeks. When they are starved after hatching, they appear to enter an “ageless state.” While they still show signs of aging, most of those signs are reversible once they find a food source and recover. Once they reach adulthood, for the most part, they have a fairly normal lifespan.

Because of that, it makes the roundworm a good model for adult aging. Baugh’s research suggests that adult aging and the pathways that extend lifespan or protect animals from aging probably evolved to protect developing animals from starvation and fluctuation in nutrient availability. “We know that reducing insulin signaling increases lifespan not just in worms but also flies, mice, and dogs,” Baugh said, “and this was discovered in worms.” Baugh speculates that additional insights into human aging will come from studying how worms respond to starvation and maintain developmental quiescence


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