High altitude–mediated immune remodeling accelerates aging
- Yu Xiao
- Yongfu Li
- Yaqi Mao
- Zichong Jin
- Mengjie Sun
- Xiangyang Wang
- Gan Zhao
- Yihong Song
- Jing Li
- Zhiying Zhang
- Lijun Liu
- Siwei Feng
- Mingzheng Liu
- Ziheng Chen
- Xinmei Guo
- Rui Yu
- Hongju Li
- Caifeng Yang
- Changfen Luo
- Jiahong Li
- Zhifang Zhao
- Juan Zhang
- Lu Cai
- Haiyang Ma
- Shuqing Li
- Shangshi Li
- Fengye Xu
- Guangwei Xin
- Qing Jiang
- Fen Huang
- Longli Kang
- Chuanmao Zhang
2026-04-22
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.