Heatwave exposure associated with accelerated biological aging in middle-aged and older adults

As global climate change intensifies, heatwaves are becoming more frequent, longer, and more severe, emerging as an important environmental stressor for human health. Previous studies have linked heatwave exposure to increased risks of cardiovascular and respiratory diseases, cognitive dysfunction, and mental health problems, while older adults are particularly vulnerable because of declining thermoregulation and reduced physiological reserve.

At the same time, population aging is accelerating, making it increasingly important to understand how environmental factors shape long-term aging trajectories. Compared with chronological age alone, biological age provides a more integrated measure of multisystem physiological deterioration, and biological age acceleration has been associated with chronic disease, functional decline, and mortality risk. "However, whether recurrent heatwave exposure accelerates systemic biological aging, and what biological mechanisms may underlie this association, remain unclear." said the author Dengyong Xu, a researcher at Zhejiang University, "Given that heat stress may disrupt metabolic homeostasis, inflammatory responses, and organ function, investigating the link between heatwave exposure and biological age acceleration, as well as the potential metabolic pathways involved, is important for identifying vulnerable populations and developing targeted climate-adaptation strategies."

This study used data from the China Health and Retirement Longitudinal Study (CHARLS), including 2,318 middle-aged and older adults aged 45 years or above, to evaluate the longitudinal association between heatwave exposure and biological age acceleration.

The researchers first applied the Klemera–Doubal method (KDM) to integrate 8 clinical biomarkers, including C-reactive protein, glycated hemoglobin, total cholesterol, triglycerides, blood urea nitrogen, serum creatinine, platelet count, and systolic blood pressure, to estimate biological age. Biological age acceleration was then calculated as biological age minus chronological age. Heatwave exposure was estimated using city-level meteorological data, including the number of heatwave events and heatwave days during the 12 months before biological age assessments in 2011 and 2015.

Twelve heatwave definitions based on different temperature percentile thresholds and event durations were used to test robustness. The study then applied a difference-in-differences design to examine whether within-individual changes in heatwave exposure were associated with changes in biological age acceleration, adjusting for baseline characteristics, lifestyle changes, weight change, and changes in depressive symptoms, with subgroup and sensitivity analyses further performed. To explore potential mechanisms, the researchers also analyzed liver transcriptomic data from aged mice exposed to heatwave conditions, identified differentially expressed genes, integrated them with aging-related genes from a public database, and used protein–protein interaction and functional enrichment analyses to investigate molecular pathways potentially linking heat exposure to biological aging.

The results showed that heatwave exposure was significantly associated with accelerated biological aging in middle-aged and older adults. Among the 2,318 participants, the mean age was 58.7 years, and the average biological age increased from 57.3 years in 2011 to 62.3 years in 2015, with 58.8% of participants showing biological age acceleration during follow-up. In the difference-in-differences analysis, increased heatwave exposure was consistently associated with higher biological age acceleration, and the association became stronger under more stringent heatwave definitions.

Under the strictest HW12 definition, defined as at least 4 consecutive days with apparent temperature above the local 97.5th percentile, each additional heatwave event was associated with a 0.531-year increase in biological age acceleration, and each additional heatwave day was associated with a 0.057-year increase, with higher odds of accelerated biological aging as well. Subgroup analyses showed stronger associations among participants with BMI ≥ 23 kg/m², urban residents, and those living in southern China or subtropical monsoon regions, suggesting that metabolic status and residential environment may shape vulnerability to heat exposure. Further biomarker analysis showed that heatwave exposure was associated with increases in total cholesterol and glycated hemoglobin, indicating potential disruption of lipid and glucose metabolism. Transcriptomic analysis of liver tissue from aged mice supported this mechanism, identifying 29 heatwave-induced differentially expressed genes enriched in lipid metabolism, atherosclerosis, and insulin resistance pathways. Overall, these findings suggest that recurrent heatwave exposure may accelerate biological aging by disrupting metabolic homeostasis.

The significance of this study lies in linking climate-change-related heatwave exposure with biological aging, suggesting that heatwaves may not only cause acute health risks but also influence aging trajectories through longer-term physiological damage. By combining a national population-based cohort with transcriptomic analysis in aged mice, the study found that recurrent heatwave exposure was associated with biological age acceleration, with stronger effects among individuals with higher BMI, urban residents, and people living in southern or subtropical regions, indicating that metabolic status and living environment jointly shape vulnerability to heat exposure.

Further biomarker and molecular analyses pointed to disruptions in lipid and glucose metabolism, supporting a potential pathway from heat stress to metabolic dysregulation and accelerated biological aging. This work provides a new perspective for understanding the long-term impact of climate change on aging-related health and highlights the need for targeted heat-health warnings, urban cooling measures, and community protection strategies for high-risk populations. However, the study remains observational and cannot establish direct causality; heatwave exposure was estimated using city-level meteorological data and may not fully capture individual exposure; biological age was based mainly on clinical biomarkers and should be further validated with molecular aging clocks and multi-omics data; and the mouse transcriptomic sample size was limited. "In the future, we will conduct long-term follow-up studies in more regions and populations, combined with individual exposure monitoring and molecular mechanism validation, to more accurately assess the impact of heat waves on healthy aging." said Dengyong Xu.