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Leveraging data derived from the China Health and Retirement Longitudinal Study (CHARLS), a large population-based cohort in China, we examined whether exposure to HWs is linked to more rapid biological aging in adults of middle and advanced age. The Klemera\u2013Doubal method (KDM) was applied to derive estimates of biological age (BA), and biological age acceleration (BAA) was calculated as biological age minus chronological age. HW exposure during the 12 months preceding BA assessments in 2011 and 2015 was quantified using 12 definitions based on different temperature threshold and duration. Longitudinal associations between HW exposure and BAA were evaluated using a difference-in-differences design. Among 2,318 participants (mean age, 58.7 years; 46.9% men), greater HW exposure was significantly associated with higher BAA. Under the most stringent (HW12; \u22654 consecutive days above the 97.5th percentile), each additional HW event and day increased BAA by 0.531 years [95% confidence interval (CI), 0.341 to 0.722] and 0.057 years (95% CI, 0.037 to 0.076). Stronger associations were observed among participants with body mass index \u2265 23 kg\/m\n                    <jats:sup>2<\/jats:sup>\n                    , urban residents, and those living in southern or subtropical regions. HW exposure was also additionally associated with higher levels of total cholesterol and glycated hemoglobin A1c (HbA1c) levels. To explore potential biological mechanisms, transcriptomic profiling was performed in aged mice exposed to HW conditions. HW exposure induced 29 differentially expressed genes enriched in lipid metabolism and insulin resistance pathways, providing biological plausibility for the observed epidemiological associations. These results suggest that recurrent HW exposure may contribute to accelerated biological aging, potentially through metabolic disruption, and highlighting the vulnerability of aging populations to climate-related thermal stress and the need for targeted climate-adaptation strategies.\n                  <\/jats:p>","DOI":"10.34133\/cbsystems.0602","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T17:12:42Z","timestamp":1778087562000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark_01","source":"Crossref","is-referenced-by-count":0,"title":["Heatwave Exposure Accelerates Biological Aging via Metabolic Dysregulation"],"prefix":"10.34133","volume":"7","author":[{"given":"Dengyong","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Colorectal Surgery, Sir Run Run Shaw Hospital, School of Medicine, \rZhejiang University, Hangzhou 310016, PR China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duanbin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Sir Run Run Shaw Hospital, School of Medicine, \rZhejiang University, Hangzhou 310016, PR China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Sir Run Run Shaw Hospital, School of Medicine, \rZhejiang University, Hangzhou 310016, PR China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingjun","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Colorectal Surgery, Sir Run Run Shaw Hospital, School of Medicine, \rZhejiang University, Hangzhou 310016, PR China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shangzhi","family":"Xie","sequence":"additional","affiliation":[{"name":"Institute of Genomic Medicine, \rWenzhou Medical University, Wenzhou 325035, PR China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Oncology, \rThe Second Affiliated Hospital of Soochow University, Jiangsu 215000, PR China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guimei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, \rRegional Medical Center for National Institute of Respiratory Disease, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, PR China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuting","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, \rRegional Medical Center for National Institute of Respiratory Disease, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, PR China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenbin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Sir Run Run Shaw Hospital, School of Medicine, \rZhejiang University, Hangzhou 310016, PR China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiapeng","family":"Bao","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery of the Second Affiliated Hospital, \rZhejiang University School of Medicine, Hangzhou 310009, PR China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1921-8897","authenticated-orcid":true,"given":"Henwei","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Electrical and Electronic Engineering and the LKC School of Medicine, \rNanyang Technological University, Nanyang 639798, Singapore."},{"name":"Division of Gastroenterology, Hepatology and Endoscopy, Department of Medicine, Brigham &amp; Women\u2019s Hospital, \rHarvard Medical School, Boston, MA 02115, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binbin","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Sir Run Run Shaw Hospital, School of Medicine, \rZhejiang University, Hangzhou 310016, PR China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","published-online":{"date-parts":[[2026,7,15]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"crossref","first-page":"27S","DOI":"10.1097\/PRS.0000000000009670","article-title":"Aging, skeletal muscle, and epigenetics","volume":"150","author":"Stewart CE","year":"2022","unstructured":"Stewart CE, Sharples AP. 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