University of Exeter: Hurricane may have caused ‘accelerated ageing’ among monkeys

Hurricane Maria hit Puerto Rico in September 2017, killing more than 3,000 people.

It also battered nearby Cayo Santiago – known as Monkey Island – which is home to a long-studied population of rhesus macaques.

The research team wanted to understand how extreme weather events might affect human health and ageing.

To do this, they looked at our close biological cousins on Monkey Island.

“While everyone ages, we don’t all age at the same rate, and our lived experiences, both negative and positive, can alter this pace of ageing,” said corresponding author Noah Snyder-Mackler, an assistant professor at Arizona State University’s School of Life Sciences.

“One negative life experience, surviving an extreme event, can lead to chronic inflammation and the early onset of some age-related diseases, like heart disease.

“But we still don’t know exactly how these events get embedded in our bodies leading to negative health effects that may not show up until decades after the event itself.”

While the final impact on the survivors’ mental and physical health remains to be tallied, a group of biologists led by Snyder-Mackler and lead author Marina Watowich – a graduate student at the University of Washington and research scientist at ASU – have looked to the rhesus macaques for the first clues.

The research team – which included the Caribbean Primate Research Center, University of Pennsylvania, University of Exeter, New York University, North Carolina Central University and the North Carolina Museum of Natural Sciences – have published one of the first results showing the effects natural disasters may have molecularly accelerated ageing in the monkeys’ immune systems.

Accelerated ageing

Despite the devastation caused by Hurricane Maria to the natural habitat and research infrastructure on Cayo Santiago, just 2.75% of the macaque population died.

In the year after the hurricane, there was no difference in survival.

But was the health of the hurricane survivors affected in other ways?

People of the same chronological age can differ in when and if they develop disease.

It is well-established that people who have suffered extremely adverse experiences have higher risk of developing heart disease and other diseases more common in older individuals.

How these detrimental experiences “get under the skin” to promote disease is still unknown. One idea is that this phenomenon is potentially due to extreme adversity “ageing” the body.

People can differ in their biological age, which can be measured by molecular signposts embedded in our genes, immune system and physiology.

“From this study, we have measured the molecular changes associated with ageing, including disruptions of protein-folding genes, greater inflammatory immune cell marker gene expression and older biological ageing,” said Watowich.

After a careful analysis of the genes expressed in the macaques’ immune cells, the researchers found that the adversity resulting from the hurricane may have accelerated ageing of the immune system.

“On average, monkeys who lived through the hurricane had immune gene expression profiles that had aged two extra years, or approximately seven or eight years of human lifespan,” said Watowich.

The findings suggest that severe weather events – which are becoming more frequent and severe due to climate change – may lead to biologically detrimental consequences for those who experience them.

Rhesus macaques share many behavioral and biological features of people, including how their bodies age, but compressed into a lifespan one quarter of ours.

By studying the macaques, the scientific team knew they could get estimates of ageing in years rather than the decades from equivalent human studies.

To test how Hurricane Maria influenced immune cell gene regulation and ageing, Watowich and the team were able to leverage a collection of blood samples and history of detailed demographic data from age-matched subsets of the Cayo Santiago rhesus macaque population.

By performing a global analysis of immune gene expression, they found 4% of genes expressed in immune cells were altered after the hurricane.

Of these, genes that had higher expression after the hurricane were involved in inflammation, and genes dampened by the hurricane were those involved in protein translation, protein folding/refolding, the adaptive immune response and T cells.

The downregulation of so-called heat shock genes, which promote the proper function of protein-making in our cells, was most affected, some with two-times lower activity after Hurricane Maria.

These genes have also been implicated in cardiovascular and Alzheimer’s disease.

Remarkably, they found a strong correlation in the hurricane exposure and ageing effects on gene expression, where the effect of the hurricane was similar to the effect of the immune system getting older.

To understand how the hurricane may have affected amounts of immune cell populations, they looked at profiles from single-cell RNA sequencing to identify genes that are preferentially expressed in key immune cell types.

“Overall, cell-specific markers of canonical pro-inflammatory immune cells, such as CD14+ monocytes, had higher expression in older individuals and those that experienced the hurricane,” said Snyder-Mackler.

“Further, expression of helper T-cell genes, an anti-inflammatory cell type, decreased in older animals and those after the hurricane.

“Together, this possibly implicates more inflammatory activity in animals after storm, similar to what we see in older individuals.”

Getting under the skin

From their long-term studies, as part of a collaboration with the Caribbean Primate Research Center, University of Pennsylvania, University of Exeter and New York University, they had four years of data prior (n = 435) and one year after (n = 108) Hurricane Maria.

They hypothesised that exposure to the hurricane would recapitulate molecular changes associated with the natural process of ageing.

“Our findings suggest that differences in immune cell gene expression in individuals exposed to an extreme natural disaster were in many ways similar to the effects of the natural ageing process,” said Snyder-Mackler.

“We also observed evidence for accelerated biological ageing in samples collected after animals experienced Hurricane Maria.”

Watowich added: “Importantly, we identify a critical mechanism – immune cell gene regulation – that may explain how adversity, specifically in the context of natural disasters, may ultimately ‘get under the skin’ to drive age-associated disease onset and progression.”

Interestingly, not all monkeys responded similarly to the hurricane. For example, some monkeys’ biological ages increased much more than others.

The team hypothesises that there may be other aspects of the monkeys’ environment that can influence their response to adversity.

For example, social support might play a critical role.

“Social support can buffer humans and other animals from the consequences of adverse events,” said Professor Lauren Brent, of the University of Exeter.

“Socially integrated people – and monkeys – live longer, healthier lives.”

The study did have its limitations, foremost, that they could not measure ageing rates within the same individuals before or after the hurricane.

For future studies, they hope the work can expand to include longer-term studies of for every individual within a population to learn more about the intersection between biological ageing, adversity and social structures and in the face of a natural disaster.

Lastly, they hope their results will encourage efforts to develop a better understanding of ageing and adversity and one day, even a successful mitigation strategy to lessen the toll from natural disasters.

“Next steps in our work will be to investigate if social factors influence the pace of ageing following natural disaster,” Professor Brent said.