Altitude

ImportanceExposure 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.ObjectiveTo 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 participantsThis 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.ExposureThe 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 measuresBiological 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.ResultsA 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 relevanceThese 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.

River deltas sustain dense human populations, major economic centres and vital ecosystems worldwide1,2. Rising sea levels and subsiding land threaten the sustainability of these valuable landscapes with relative sea-level rise and associated flood, land loss and salinization hazards1-3. Despite these risks, vulnerability assessments are impeded by the lack of contemporary, high-resolution, delta-wide subsidence observations4. Here we present spatially variable surface-elevation changes across 40 global deltas using interferometric synthetic aperture radar. Using this dataset, we quantify delta surface-elevation loss and show the prevalence and severity of subsidence in river deltas worldwide. Our analysis of three key anthropogenic drivers of delta elevation changes shows that groundwater storage has the strongest relative influence on vertical land motion in 10 of the 40 deltas. The other deltas are either influenced by multiple drivers or dominated by sediment flux or urban expansion. Furthermore, we find that contemporary subsidence surpasses absolute (geocentric) sea-level rise as the dominant driver of relative sea-level rise for most deltas over the twenty-first century. These findings suggest the need for targeted interventions addressing subsidence as an immediate and localized challenge, in parallel with broader efforts to mitigate and adapt to climate change-driven global sea-level rise.

Hypobaric hypoxia, a defining feature of high-altitude environments, poses a considerable physiological challenge to both humans and rodents. To withstand hypoxic stress, mammals have developed cellular and systemic adaptations that not only safeguard against acute and future episodes of oxygen deprivation but may also enhance overall resilience and functional capacity. A central aim of current research is to harness these health-promoting effects of hypoxic exposure as a therapeutic strategy for a range of medical conditions. To date, much of the evidence regarding the safety and efficacy of such interventions derives from rodent studies. In this review, we summarize current knowledge on hypoxia tolerance, oxygen transport, and oxygen consumption in humans, rats, and mice, and evaluate the extent to which findings from rodent models can be extrapolated to humans. While the anatomical, physiological, and molecular foundations of oxygen transport and utilization are broadly conserved across species, there are important quantitative differences-largely linked to body-mass variation-as well as qualitative distinctions. Mice that evolved in high-altitude environments, display remarkable hypoxia tolerance. Their physiological repertoire includes highly efficient pulmonary gas exchange, metabolic downregulation, and substantial plasticity of the mitochondrial electron transport system under hypoxic conditions. In contrast, rats exhibit heightened vulnerability in hypoxia, manifesting as right ventricular hypertrophy, excessive erythropoiesis, and myocardial injury. These interspecies differences highlight that the robust hypoxia tolerance of mice-and the potentially comparatively greater susceptibility of rats than humans-must be carefully considered when translating findings from rodent hypoxia research into human contexts.