Science advances · 2026
High altitude-mediated immune remodeling accelerates aging.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
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Xiao Yu, Li Yongfu, Mao Yaqi, Jin Zichong, Sun Mengjie, Wang Xiangyang, Zhao Gan, Song Yihong, Li Jing, Zhang Zhiying, Liu Lijun, Feng Siwei, Liu Mingzheng, Chen Ziheng, Guo Xinmei, Yu Rui, Li Hongju, Yang Caifeng, Luo Changfen, Li Jiahong, Zhao Zhifang, Zhang Juan, Cai Lu, Ma Haiyang, Li Shuqing, Li Shangshi, Xu Fengye, Xin Guangwei, Jiang Qing, Huang Fen, Kang Longli, Zhang Chuanmao
Аннотация
High altitude-associated 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-associated pathophysiological processes.