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Adv."],"published-print":{"date-parts":[[2026,4,24]]},"abstract":"<jats:p>High altitude\u2013associated pathophysiological processes may potentially accelerate aging trajectory, while evidence remains limited. We present immune landscape characterization in human populations residing at 3656-meter (Lhasa) and 5070-meter (Tuiwacun) elevations on the Qinghai-Tibet Plateau, complemented by multiorgan single-cell RNA sequencing and spatially enhanced resolution omics sequencing (Stereo-seq) of mice under simulated 5000-meter hypoxic conditions. Comparative analysis revealed significantly elevated neutrophil proportions in high-altitude population (HAP) cohorts relative to low-altitude population cohorts. Notably, aging-associated immune cells (AICs) including exhausted T cells, age-associated B cells, and high-aging-score immune cells showed marked enrichment in HAP cohorts, a pattern conserved in mouse models. Stereo-seq analyses further identified coordinated niche interactions between AICs and aging-related intestinal epithelial cells, suggesting accelerated gut aging trajectories. Our work establishes the multiomics framework for high-altitude immune remodeling while providing mechanistic insights into high altitude\u2013associated pathophysiological processes.<\/jats:p>","DOI":"10.1126\/sciadv.aeb5599","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T17:59:52Z","timestamp":1776880792000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["High altitude\u2013mediated immune remodeling accelerates aging"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3107-411X","authenticated-orcid":true,"given":"Yu","family":"Xiao","sequence":"first","affiliation":[{"name":"The Academy for Cell and Life Health, Faculty of Life Science and Technology and Medical School, Kunming University of Science and Technology, Kunming 650500, 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