In many animals, having many offspring is linked to a shorter lifespan. This is largely because animals that bear many offspring allocate nutritional and metabolic resources for reproduction at the cost of their own longevity. It’s thought that the insulin and the insulin-like growth factor signaling pathway underlies the anti-correlation between reproduction and shortened lifespan.

A new study finds that this relationship does not apply to ants. Rather, ants couple egg-laying with a long life. The queens—the only individuals in a nest that reproduce—can live up to 30 times longer than their genetically identical worker sisters. Indeed, queen ants exhibit high metabolism for reproduction without undergoing aging.

An insulin-suppressing protein may be at the center of this process for ants, and could provide clues about aging in other species. The ants generate an anti-insulin protein that blocks only part of the insulin pathway responsible for aging. The findings of the study show that ant queens implement a dual-control system for insulin—the metabolism-controlling hormone that explains much of the trade-off between reproduction and lifespan. More specifically, queens massively boost their insulin production, which promotes egg development while their ovaries produce an insulin blocker that slows down the aging process.

This work is published in Science in the paper, “Insulin signaling in the long-lived reproductive caste of ants.”

“Hopefully this finding allows us to better understand the aging process in many animals,” said Hua Yan, PhD, assistant professor of biology at the University of Florida.

In Harpegnathos saltator ants, workers duel with their antennae to establish new leadership after the death of their queen. Winners (or pseudoqueens) acquire queen-like behaviors, including laying eggs, and their life expectancy increases from seven months to four years. [Giacomo Mancini/NYU]

In ant colonies, reproductive activity is limited to one or a few queens who can live for decades—many lifetimes beyond a colony’s nonreproductive female workers—and lay millions of eggs. In ant species like Harpegnathos saltator, workers can switch castes and become reproductive pseudo-queens, or gamergates, when a queen dies or is removed. Despite being born as workers, gamergates can live up to five times longer than their previous counterparts. What’s more, gamergates can revert to workers (revertants) when placed in a colony with an established worker caste, returning to a shortened life span. How this reproduction-associated longevity in these animals is regulated, particularly during active reproduction, remains unclear.

“It’s straightforward, the pseudo-queen is reproductive, so they need insulin. But insulin normally shortens lifespan, yet they have a much longer lifespan—why?” Yan asked. “There must be something in the insulin signaling of the ants that differentially regulates reproduction and longevity.”

To evaluate the relationship between reproduction and longevity, Yan and colleagues performed bulk RNA sequencing on tissues important for reproduction and metabolism from worker, gamergate, and revertant H. saltator ants and compared gene expression during caste switching. As expected, they found that insulin was upregulated to promote oogenesis in gamergates, however, this did not lead to a shorter lifespan as it does in other animals. The authors propose that part of the insulin signaling pathway (the branch that activates the protein kinase AKT is inhibited in the fat body of gamergates and that this may be mediated by a protein Imp-L2. According to the authors, decreased activity of AKT may enable H. saltator queens and pseudo-queens to live longer.

The research team found this extra layer of control in the form of the insulin blocker Imp-L2, which is produced by the newly active ovaries of the pseudo-queen. This insulin blocker slows down the part of the insulin pathway normally responsible for accelerating the aging process, but leaves the reproduction-boosting side of insulin signaling intact.

Whether mammals, including humans, could ever benefit from partially blocking the insulin pathway remains an open question. Calorie restriction, a process that may extend lifespan, has been shown to decrease insulin production.

“Our work also illustrates the importance of using the appropriate model systems to ask questions about essential biological questions. For instance, most manipulations of longevity in animals like mice or flies usually extend their lifespans by 10–20%. Ants exhibit a remarkable 500% increase in longevity, which makes studying them much more powerful,” added Claude Desplan, PhD, professor of biology and neural science at New York University.

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