New Study Finds Survivors of Weather-Related Disasters May Age at Accelerated Rates

Posted February 08, 2022, 5:28PM
A rhesus macaques mother with infant.

Findings Published in Proceedings of the National Academy of Sciences

When Hurricane Maria slammed into Puerto Rico in September 2017, it killed more than 3,000 people, knocked out power to nearly all the island’s 3.4 million residents and caused more than $100 billion in damages. 

It also impacted nearby Cayo Santiago, known as Monkey Island, which is home to a population of rhesus macaques that have inhabited the island since 1938.

A research team from Arizona State University (ASU), Caribbean Primate Research Center, University of Pennsylvania, University of Exeter, New York University, North Carolina Central University (NCCU) and the North Carolina Museum of Natural Sciences sought to study how extreme weather may affect human health and the aging process.

The group took a closer look at the close evolutionary cousins of humans – the rhesus macaques 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 aging,” said corresponding author Noah Snyder-Mackler, an assistant professor at ASU’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 human survivors’ mental and physical health remains to be tallied, the group of researchers led by Snyder-Mackler and lead author Marina Watowich, a graduate student at the University of Washington and research scientist at ASU, have published their initial results in the Proceedings of the National Academy of Sciences, which shows the effects of this recent natural disaster may have molecularly accelerated aging in the monkey’s immune systems.

Results from the paper, entitled “Natural disaster and immunological aging in a nonhuman primate,” are especially pressing with hurricanes and other extreme weather events becoming stronger and more common with climate change.

“We know that when humans experience traumatic life events, it can have lasting impacts on their health and mental state,” said Julie Horvath, Ph.D., research associate professor of biological and biomedical sciences at NCCU and head of genomics and microbiology at the N.C. Museum of Natural Sciences. “Our research underscores the importance of ongoing studies in these rhesus macaque monkeys to help us better understand the factors impacting health and aging across all primates, including humans.”

Accelerated aging

Although Hurricane Maria caused devastation to the natural habitat and research infrastructure on Cayo Santiago, only 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?

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 ‘aging’ 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 aging, including disruptions of protein-folding genes, greater inflammatory immune cell marker gene expression and older biological aging,” 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 aging 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 7-8 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.

Biological aging

Approximately 1,800 rhesus macaques live on the Cayo Santiago island.

“Cayo Santiago was the first part of Puerto Rico hit by Hurricane Maria and took on the full force of the category 4 storm,” said Snyder-Mackler. “The hurricane destroyed homes and infrastructure across Puerto Rico, and on Cayo Santiago it decimated most of the vegetation, as well as the water cisterns and research infrastructure needed to maintain the field station.”

The 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 research team knew they could get estimates of aging in years rather than the decades from equivalent human studies.

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

A global analysis of immune gene expression exposed 4% of genes expressed in immune cells were altered after the hurricane. Genes with higher expression after the hurricane were involved in inflammation and genes dampened by the hurricane were included in protein translation, protein folding/refolding, the adaptive immune response and T cells.

The down regulation of so-called heat shock genes, which promote the proper function of protein-making in our cells, were most affected including some with two-times lower activity after Hurricane Maria. These genes have also been implicated in cardiovascular and Alzheimer’s disease.

Remarkably, the group found a strong correlation in hurricane exposure and aging 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 to Hurricane Maria (n = 435) and one year after (n = 108) Hurricane Maria.

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

“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 aging process,” said Snyder-Mackler. “We also observed evidence for accelerated biological aging in samples collected after animals experienced Hurricane Maria.”

“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,” Watowich noted.

Interestingly, not all monkeys responded similarly to the hurricane. For instance, some monkeys’ biological ages increased much more than others. The team hypothesizes that there may be other aspects of the monkey’s environment that can influence their response to adversity.

For example, similar to studying humans, social support is a critical aspect of the ability to help cope and deal with adversity. It is possible that monkeys with greater social support after the storm were better able to overcome any detrimental effects–an aspect the team hopes to investigate soon. The study had its limitations, including not being able to measure aging rates within the same individuals before or after the hurricane.

For future studies, the group hopes their work can expand to include longer-term studies for every individual within a population to learn more about the intersection between biological aging, adversity and social structures and in the face of a natural disaster. In addition, they hope their results will encourage efforts to develop a better understanding of aging and adversity and one day, even a successful mitigation strategy to lessen the toll from natural disasters.

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