Natural disaster and immunological aging in a nonhuman primate

Abstract

Weather-related disasters are increasing in frequency and severity, leaving survivors to cope with ensuing mental, financial, and physical hardships. This adversity can exacerbate existing morbidities, trigger new ones, and increase the risk of mortality-features that are also characteristic of advanced age-inviting the hypothesis that extreme weather events may accelerate aging. To test this idea, we examined the impact of Hurricane Maria and its aftermath on immune cell gene expression in large, age-matched, cross-sectional samples from free-ranging rhesus macaques (Macaca mulatta) living on an isolated island. A cross section of macaques was sampled 1 to 4 y before (n = 435) and 1 y after (n = 108) the hurricane. Hurricane Maria was significantly associated with differential expression of 4% of immune-cell-expressed genes, and these effects were correlated with age-associated alterations in gene expression. We further found that individuals exposed to the hurricane had a gene expression profile that was, on average, 1.96 y older than individuals that were not-roughly equivalent to an increase in 7 to 8 y of a human life. Living through an intense hurricane and its aftermath was associated with expression of key immune genes, dysregulated proteostasis networks, and greater expression of inflammatory immune cell-specific marker genes. Together, our findings illuminate potential mechanisms through which the adversity unleashed by extreme weather and potentially other natural disasters might become biologically embedded, accelerate age-related molecular immune phenotypes, and ultimately contribute to earlier onset of disease and death.

Fig. 1.

Hurricane Maria caused severe destruction to Cayo Santiago and was associated with altered immune cell gene regulation. (A) Hurricane Maria struck the island of Cayo Santiago on September 20, 2017, causing severe devastation to the vegetation and substantial remodeling of the environment. Aerial photographs show Cayo Santiago in August 2008 (Left) and January 2020 (Right). Photos reused with permission of Joyce Cohen, WOM Productions, and Michelle Skrabut La Pierre. (B) Vegetation, as measured by NDVI, decreased by 63% due to the storm (t test, P = 3.7 × 10⁻²⁵). (C) Temperature in areas that lost vegetation due to Hurricane Maria (i.e., de-vegetated) were significantly warmer than areas still vegetated after the storm (t test, P < 1 × 10⁻¹⁰). (D) Peripheral whole blood was collected cross-sectionally from the rhesus macaque population on Cayo Santiago island approximately annually 1 to 4 y before (n = 435) and 1 y after (n = 108) Hurricane Maria struck the island. Animals sampled posthurricane were an average of 0.89 y younger than animals sampled prehurricane (median age prehurricane = 6.94, median age posthurricane = 6.05, t test of means P value = 1.16 × 10⁻³). (E) PC3 of global gene expression captures the shared effects between increasing age (β = −0.19, P = 8.96 × 10⁻⁸) and (F) exposure to Hurricane Maria (β = −1.79, P = 9.12 × 10⁻⁵) on immune gene expression. PC3 explains 3.4% of the overall variance in gene expression.

Fig. 2.

Similar effects of Hurricane Maria and aging on immune cell gene expression. The standardized effect sizes of experiencing Hurricane Maria on immune gene expression are positively correlated with standardized effect sizes of aging on immune gene expression (r = 0.23, P = 1.33 × 10⁻⁸⁴). Genes that are significantly associated (FDR < 10%) with aging and Hurricane Maria correlate even more strongly (r = 0.58, P = 1.05 × 10⁻¹⁰). Genes significantly associated with both effects are colored purple. Inset plots show schematics of the gene expression differences represented in each quadrant.

Fig. 3.

Hurricane Maria disrupted genes involved in protein homeostasis and was associated with accelerated gene expression aging. (A) Aging and experiencing Hurricane Maria were associated with reduced expression of key molecular chaperone proteins. Genes shown were differentially expressed with aging and/or hurricane exposure (FDR < 10%). (B) Molecular chaperone proteins in the protein homeostasis pathway that were significantly associated with the hurricane and aging. These proteins promote proper folding of client proteins and clear terminally misfolded proteins from the cell. (C) Predicted biological ages based on gene expression profiles for prehurricane (green) and posthurricane (brown) samples. Posthurricane samples have a predicted biological age that is, on average, 1.96 y greater than their chronological age (P = 0.0003).

Fig. 4.

Aging and experiencing Hurricane Maria were associated with broadly similar immune cell marker gene expression. Shaded points represent marker genes that were significantly differentially expressed (FDR < 10%) across aging (A) and Hurricane Maria (B). Open points represent marker genes that were not significantly associated with the effect of aging or hurricane exposure. Asterisks denote cell types for which differentially expressed marker genes were either positively or negatively enriched (p_BH < 0.05).