Abstract
IMPORTANCE: Exposure to high altitudes elicits multiple adaptive mechanisms that intricately impact the entire body, causing deleterious health outcomes. However, high-altitude exposure effects on accelerated aging and aging-related changes remain uncertain. OBJECTIVE: To comprehensively assess the associations of high-altitude exposure with overall aging and related changes and to provide insights into the treatment and prevention of aging-associated deficits in populations living in high-altitude areas. DESIGN, SETTING, AND PARTICIPANTS: This population-based cross-sectional study used data from 2 prospective studies in Western China: West China Natural Population Cohort (WCNPCS) and West China Health and Aging Trend (WCHAT). The WCNPCS cohort was constructed from May 2019 to June 2021. Data were collected from participants aged 18 years and older in 4 populous regions (Mianzhu, Longquan, Pidu, and Ganzi) in Sichuan Province. The WCHAT was initiated in 2018 and recruited participants aged 50 years and older from various regions (Sichuan, Yunnan, Guizhou, and Xinjiang). Participants were selected via sequential cluster sampling from the permanent residents of the participating community. Data for the present study were analyzed between March and October 2024. EXPOSURE: The participants' altitudes were determined using the global Shuttle Radar Topography Mission 4 data based on residential addresses. High-altitude areas refer to regions with altitudes of greater than or equal to 1500 m (4921 feet) above the mean sea level. MAIN OUTCOMES AND MEASURES: Biological aging (BA) and aging acceleration (AA) were measured through the Klemera-Doubal Biological Age (KDM-BA) and PhenoAge methods. Multidimensional aging-related metrics were based on questionnaire, measurement, and self-report. RESULTS: A total of 9846 participants from the WCNPCS cohort (mean [SD] age, 55.73 [11.06] years; 6730 women [68.35%]) and 3593 participants from the WCHAT cohort (mean [SD] age, 62.27 [8.40] years; 2253 women [62.71%]) were included. The participants living at high altitudes presented increased KDM-BA acceleration by 0.85 years for the WCNPCS cohort and 0.71 years for the WCHAT cohort. The PhenoAge results were similar, with even larger effect sizes (WCNPCS, β, 2.08 years; 95% CI, 1.77-2.39 years; WCHAT, β, 2.23 years; 95% CI, 1.91-2.54 years). The association between high-altitude exposure and biologically accelerated aging was particularly pronounced among smokers. Associations between high-altitude exposure and various multidimensional aging-related metrics were also observed. CONCLUSIONS AND RELEVANCE: These findings suggest that extended periods at high altitudes may hasten BA and contribute to the onset of aging-related illnesses. Implementing public health interventions for individuals residing in high-altitude regions may aid in alleviating the disease burden within these communities.