What can ants, bees, and other social insects teach us about aging? – Science Magazine

At almost 2 centimeters, the queen of the Texas leafcutter ant (Atta texana) is far bigger than her workers. She also has a longer life span.

By Yao-Hua LawMar. 25, 2021 , 2:00 PM

A small room in the University of Regensburg is home to more than 50 boxes of black, strikingly slender ants. Native to Central America, the clonal ant Platythyrea punctata has evolved a trait rare among ants: It can produce daughters from unfertilized eggs. A P. punctata colony can consist entirely of clones, produced by one or two dominant females. That uniformity underscores a mystery.

What is really fascinating is that they are the same genetically, says evolutionary biologist Abel Bernadou, pointing to the 30 or so ants in a box, but depending on their jobs, they will have totally different life spans. Members of the colonys working caste, which nurse the brood, hunt for food, and defend the nest, die within 7 months, even when well-fed and protected in the lab. But ants in the reproductive caste, whose sole job is to lay eggs, can live 10 to 16 months.

To Bernadou, the questions raised by those disparities are irresistible. What causes some ants to live twice as long as nest mates that have exactly the same genome? And how can reproduction, a taxing effort that speeds up aging in most animals, make these ants live longer instead?

Bernadou and his myrmecologist colleagues at Regensburg are part of a small cadre of researchers who have turned to social insectsants, bees, and termitesto help unravel the mysteries of aging. Its a developing field that rarely features in conferences on aging biology, where the spotlight is on mice, Drosophila fruit flies, and the minuscule nematode Caenorhabditis elegansthree species researchers have probed and tweaked for well over half a century to learn what controls their life spans.

Many who study those species have yet to be convinced that social insects have something important to contribute. They think its fun and worthwhile to know the diversity of aging, says biologist Gro Amdam, who studies aging in bees at the Norwegian University of Life Sciences and Arizona State University, Tempe. But they dont think we will make major discoveries in social insects that are relevant to their work.

In the western honey bee (Apis mellifera), queens (middle) live longer than workers (top) and drones (bottom).

But Amdam and other social insect researcherswho this month published a big batch of findings ina thematic issue on aging and socialityin thePhilosophical Transactions of the Royal Society Bsay they promise new ways to understand aging. One reason is that many social insects live far longer than the more popular model organisms. Honey bee queens live up to 5 years, and termite and ant queens more than 20.Drosophila, by contrast, has a life span of 13 weeks at most, andC. elegansa mere 18 days. If you want to know how to die quickly, then work onDrosophila, quips evolutionary biologist Laurent Keller, who studies aging in ants at the University of Lausanne.

Even more intriguing is the fact that aging in social insects is plastic, changing with social context. Few social insects are as homogenous as clonal ants, but in most, queens and workers have very similar genomes, because all colony members are offspring of one or several queens. Yet whereas queens seem to stay youthful through their long lives, workers age quickly and die fast. And within a colony, a workers job determines its life span, even though by and large all workers are siblings. Scientists can rush, slow, or even reverse aging in ants and bees simply by having them mate or changing their tasks.

Revealing the molecular mechanisms behind these strange phenomena may ultimately shed more light on aging in general, including in humans, saysmolecular biologist Roberto Bonasioat the University of Pennsylvania, who studies epigenetics in mammals, flies, and ants: Thats the idea.

Aging, or senescence,is a progressive loss of function and performance with time. It saps the individuals capacity to withstand stress, fight diseases, heal wounds, or learn new skills. But must we age? Why did organisms not evolve to maintain their youthlike vigor until theyre about to die?

Rather counterintuitively, scientists argue aging is the outcome of natural selection, which favors genes that help an organism survive to reproductive age. Once the individual has produced offspring, selection for survival weakens, which opens the door for injurious genetic effects to accumulate. Aging sets in.

The strong selection to survive until reproduction may favor so-called pleiotropic genes, which are helpful in early life but harmful later on. An example is theclk1gene inC. elegans, which is known to boost the nematodes metabolism. The gene promotes early reproduction and gives individuals a fitness edge over competitors, but shortens their life span by 40%, in part because it speeds the buildup of harmful metabolic byproducts.

Scientists have suggested organisms living in more precarious environmentsfor instance ones thick with predators or competitorsexperience higher selection for survival and reproduction early in life, at the cost of faster aging later on. This so-called extrinsic mortality hypothesis is often used to explain why animals that fly, live underground, or are venomousand as a result face fewer threatsalso seem to live longer and presumably age less rapidly. Think of bats, which live far longer than other mammals of similar size.

The average maximum life span for solitary insects is much less than for reproductive individualsqueens, kings, and some workersamong social insects.

Within social insect species, the life span of reproductive individuals far exceeds that of those that do not produce offspring.

(Graphic) N. Desai/Science; (Data) L. Keller and M. Genoud, Nature, 389, 958 (1997); Korb et al., Phil. Trans. R. Soc. B, 376 (2021); Kramer et al., Experimental Gerontology, 85, 18, (2016); Oettler et al., Current Opinion in Insect Science, 16, 58, (2016); Thorne et al., Journal of Animal Ecology, 71, 1030, (2002); Peeters et al., Insectes Soc., 47, 325 (2000)

Back in the 1990s, Keller realized social insects offered an interesting way to test the extrinsic mortality hypothesis, he says. Safely ensconced in their nests and guarded by a legion of workers, ant queens are assumed to face a much lower risk of predation and disease, and thus of dying, than insects living a solitary life.

Keller and his Lausanne colleague Michel Genoud collected life span records of queens in 61 species of ants, termites, and the honey bee, and compared these with adults of 81 solitary insect species. On average,queens live 5 to 11 years, whereas solitary insects live only months, they reported in a 1997 paper. Everything was as the hypothesis predictedand the paper kick-started aging research in social insects.

The field facesplenty of challenges. Insect queens and kings are rare, which limits studies sample sizes. And keeping colonies of social insects alive can be laborious. At Regensburg, evolutionary biologist Jan Oettler and graduate student Luisa Jaimes maintain 200Cardiocondyla obscuriorant colonies that they need to feed and clean several times weekly over the 6 months or more that their queens live. By contrast, to grow hundreds ofDrosophilamaggots into adults, you only need a bottle, premade fly food, and 10 days. One nasty reviewer asked why, since we cant get the numbers, do we still useCardiocondylaa tiny tropical antinstead ofDrosophila, says myrmecologist Jrgen Heinze, who has been studying the ants for 30 years at Regensburg. They cant see the benefits.

Lagging experimental techniques are a problem as well. In mice, scientists can document physiological aging in urine and blood samples; inDrosophilaandC. elegans, they can insert molecular tags into cells that show gene expression in real time. Such molecular clocks dont exist yet for ants and termites. Thats a problem because aging isnt always a linear process: Queen ants often churn out eggs for months or years without visible aging, only to drop dead abruptly. Without reliable and nonlethal ways to trace aging or physiological changes at the molecular level, comparisons between old and young individuals are questionable. If you have a 10-day-old worker, to what do you compare it? A 10-day-old queen? Or a queen that has lived the same proportion of its average life span? Keller asks. This is difficult.

A worker of the Indian jumping ant (Harpegnathos saltator) tends the brood. When members of this species lay eggs, their brains develop40% more of a type of protective cell called ensheathing glia, researchers have found.

Gene editing would be a game changer for these studies, Oettler says, enabling scientists to disable specific genes and watch for effects on aging. But it has barely started to be used in social insects. Scientists only created thefirst genetically modified honey bees in 2014, andtwospeciesof genetically engineered antsin 2017. Amdam would love to see transgenic technology developed for free-flying honey bees, allowing real-world experiments on aging. But beekeepers staunchly oppose genetic modification, which they worry could affect their colonies, and regulators are wary. The moment you say free-flying transgenic bee, its no-no, Amdam says.

One way to speed progress, Bonasio says, is to consolidate our efforts on one or two species so that more [molecular] tools are available to everybody. But Heinze says researchers should embrace the bewildering variety of life histories and aging patterns seen in social insects. There is no standard ant, he says; for understanding the diverse causes and effects of aging, plurality is best.

Despite the challenges, scientists are starting to link aging patterns in social insects to the underlying molecules. One oddity theyre probing is the link between reproduction and longevity.

In most animals, high fecundity almost universally comes with a quick burnout; red deer, for example, age faster if they reproduce early. But social insect queens buck the trend: Reproduction stretches their life span rather than snipping it. For example, a 2005 study by Heinzes team found thatC. obscuriorqueens that mated had life spans 44% longer than virgin queens (26 weeks versus 18). And thats despite these mated queens hectic lifestyles: They laid up to five times more eggs, and at faster rates, than queens that did not mate or were mated with sterile males.

Other scientists have discovered that procreation also extends the life spans of queens of other ant species, honey bee queens, and termite queens and kings. In species where a limited number of workers in a colony can also reproduce, such as theP. punctataants that Bernadou studies, those that reproduce live longer, too.

In termites, reproduction may blunt the impact of transposons, bits of DNA that jump through the genome, disrupting genes and, at least in humans andC. elegans, promoting aging.Judith Korb, who studies aging in termites at the Albert Ludwig University of Freiburg, compared transposon activity in two termite species. In the species with sterile workers, older workers have higher transposon activity; in the species where older workers can reproduce, they show better defense against damage from transposons.

Workers of the Japanese termite (Reticulitermes speratus) cant repair oxidative damage as well as queens (not shown) and live shorter lives.

Social insects brains appear to benefit from sex as well. WhenHarpegnathos saltatorants, also known as Indian jumping ants, lay eggs,their brain develops 40% more of a type of protective cellcalled ensheathing glia, Lihong Sheng, a postdoc in Bonasios lab, reported in August 2020. A decline of these cell types is associated with aging in flies and cognition loss in mice. If we know what the ants themselves use to control the number of [ensheathing glia] in the brains, Bonasio says, it could point to similar mechanisms in flies, mice, and maybe in humans. (Bonasio is now studying the phenomenon inDrosophilaflies; the ants showed us the way but once I know what the pathway is, I prefer to do the experiment inDrosophila because it is easier, he says.)

A workers job can also slow or speed up its aging. Honey bee workers, for instance, start out as nurse bees that stay in the hive and tend to the brood and the queen. About 3 weeks into their lives, they become foragers that fly out to collect food. Various studies show that nurse bees do not age, but foragers do so rapidly, declining in flight performance, immunity, and learning.

Amazingly, that process can be reversed. When a hive needs more nurse bees, foragers can switch back to their former roles. When Amdam removed nurse bees from hives, foragers were forced to revert to their former rolesand they also recovered their youthful traits. Such reverted nurse bees produce more cells that mop up pathogens, Amdam says. They also regain high levels of vitellogenin, a multipurpose, Swiss knife sort of protein that regulates a bees changing roles across its lifetime and declines as the insects age. She has found that reverted nurse bees learn faster than foragers of the same age and that their brains have more proteins associated with cellular stress resilience and repair.

These job switches in bees dont only mean a new line of work; they also bring a different set of interactions with other members of the colony. Amdam thinks a bees social life plays an important role in its longevity. Social contact is also known to affect human physiological and mental health, and loneliness has been identified as a risk factor for cognitive declinea provocative similarity. Although scientists have yet to determine how sociality can affect insects life span at the molecular level, it certainly has peoples attention, Amdam says.

Several papersin this months theme issue of thePhilosophical Transactionsdelve deeper into the molecular control of aging in social insects. Onecompared gene-expression patterns between young and old individualsof six species of ants, bees, and termites, for example. The study measured the activity of two biochemical pathways, both ubiquitous in animals, that detect nutrients and regulate cell development. Scientists had previously found strong links between these pathways and life spans in flies and other solitary insectsbut not in social insects.

In the new study, however, they scrutinized parts and products of the same pathways that had been largely neglected in aging research, and found genes and proteinsincluding vitellogeninthat strongly associate with aging in social insects. These results reinforce the need to cast a wide net and study aging in many species, says Korb, lead author of the new paper.

Thomas Flatt, who studies the genetics of aging inDrosophilaat the University of Fribourg, is one of the researchers who has been won over by the promise of social insects. Flatt has been working with Korb, Heinze, and other researchers in a6.2 million project funded by the German Research Foundationto study the unusual relationship between fecundity and aging in social insects. The genomic revolution will eventually help the field take flight, Flatt predicts, and give scientists a much better understanding of how aging works across the animal kingdom. My dream is that we will discover stuff in ants that is universally important, he saysthings we dont even know existed inDrosophila.

Correction, 26 March 2021, 1:35 p.m.: This story previously discussed the creation of transgenic ants in 2017.They were genetically engineered, but not transgenic.

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What can ants, bees, and other social insects teach us about aging? - Science Magazine