New research on fruit flies provides the first reliable animal model for studying our bodies’ reactions to loneliness.

Social isolation; we’re all probably more intimately familiar with the term, given these past two years, than we’d like to be. But we’re not the only ones who suffer when we’re separated from our group. New research on fruit flies shows that they as well sleep too little and eat too much when deprived of social interactions. The paper also reports on changes in gene expression, neural activity, and behavior seen in the flies.

The findings are of interest to all of us today, as they point to novel ways of understanding the effects loneliness has on our bodies. They’re also relevant to scientists directly studying fruit flies, or those whose work involves fruit flies, as accounting for these effects would go a long way to improving the reliability of our conclusions.

Flyin’ solo

“Flies are wired to have a specific response to social isolation,” says corresponding author Michael W. Young, the Richard and Jeanne Fisher Professor and head of the Laboratory of Genetics at Rockefeller. “We found that loneliness has pathological consequences, connected to changes in a small group of neurons, and we’ve begun to understand what those neurons are doing.”

It’s not a stretch to say that most of us have had trouble maintaining our pre-lockdown sleep schedule. Many of us are also overeating, or eating at odd hours, and have gained weight. The team behind this study suspected that the social isolation brought about by the lockdown is, in itself, to blame for this. It seems like their hypothesis panned out, as the results describe how chronic separation from the group can have measurable effects on the body (at least in fruit flies). These effects include changes in gene expression, neural activity, and behavior.

Fruit flies (Drosophila melanogaster) are a very social species. They forage and eat in groups, have complex mating rituals, and even engage in some tiny fights from time to time. However, they spend most of their time (up to 16 hours each day) sleeping — also in groups. They have long been a model organism for researchers in various fields of biology. So, when the team turned to them to test their hypothesis.

“Over and over again, Drosophila have put us on the right track,” says Young. “Evolution packed a great deal of complexity into these insects long ago and, when we dig into their systems, we often find the rudiments of something that is also manifest in mammals and humans.”

“When we have no roadmap, the fruit fly becomes our roadmap,” adds lead author Wanhe Li.

The team first compared how fruit flies behave under various lockdown conditions. Flies were kept together in groups of various sizes, ranging from several individuals to a single fly, for a week. For the most part, the insects didn’t have any problems; even flies who were kept with a single other fly didn’t show any distress. However, those that were entirely isolated from their peers started sleeping less and eating more as the trial progressed.

The team further reports finding changes in the expression patterns of a constellation of genes linked to starvation in the brains of these lonely flies. This, they argue, is the genetic link between social isolation and the observed biological changes. One group of cells known as P2 neurons were involved in changing the flies’ feeding and resting behavior. When the P2 neurons were disabled in chronically-isolated flies, they reverted to more normal feeding and sleeping patterns. Amplifying their activity in flies that were only isolated for one day caused them to exhibit the sleeping and overfeeding behavioral patterns of flies who had been isolated for a full week.

“We managed to trick the fly into thinking that it had been chronically isolated,” says Wanhe Li. “The P2 neurons seem to be linked to the perception of the duration of social isolation, or the intensiveness of loneliness, like a timer counting down how long the fly has been alone.”

While these findings haven’t been replicated in humans, the team is confident that more or less the same biological mechanisms seen in these flies operate in isolated humans as well. It’s not the same as confirming that people who ate more and slept less during the lockdown did so because of their P2 neurons — but it’s a starting point, at least.

“Clinically-oriented studies suggest that a large number of adults in the United States experienced significant weight gains and loss of sleep throughout the past year of isolation precautions due to COVID-19,” Young says. “It may well be that our little flies are mimicking the behaviors of humans living under pandemic conditions for shared biological reasons.”

The paper “Chronic social isolation signals starvation and reduces sleep in Drosophila” has been published in the journal Nature.