Jun Yan, PhD | Chinese Academy of Medical Sciences; Diangeng Li, PhD; Sijie Li, MD; Youliang Sun, PhD; Zechao Gao, MS; Cong Li, PhD Candidate; Wenqin Wang, PhD Candidate
Competition Sponsor: Chinese Academy of Medical Sciences
Awardee Year: 2025
Immunosenescence, the age-related decline in immune function, is a major driver to systemic aging, increasing susceptibility to infections, reducing vaccine efficacy, and elevating the risk of age-related diseases. Key hallmarks include skewed hematopoietic stem cell (HSC) differentiation, thymic atrophy, and chronic inflammation. The hypoxic microenvironment has emerged as a critical yet poorly understood regulator of this process. Although hypoxia can bidirectionally modulate aging and immunity through metabolic, epigenetic, and inflammatory pathways, its systemic effects and therapeutic potential remain largely unexplored, with current evidence primarily derived from in vitro studies. This project aims to systematically investigate the potential of intermittent hypoxia (IH) to reverse immunosenescence in vivo. We will establish an IH training protocol in aged mice to comprehensively assess its effects on key immunological parameters. Specifically, we seek to determine the impact of this intervention on bone marrow HSC aging, T-cell receptor (TCR) repertoire diversity, and the capacity to generate effective vaccine responses. Furthermore, we will elucidate the underlying molecular mechanisms by which IH attenuates HSC aging and chronic inflammation while promoting lymphoid differentiation. To facilitate clinical translation, the project will also develop a smart, patented device for safe and personalized delivery of IH training, and evaluate the effect of hypoxia preconditioning on vaccine response rates in elderly human subjects, thereby establishing a direct foundation for translational application. This research aims to provide a robust theoretical basis for the development of hypoxic adaptation-based immune interventions against aging, with significant scientific and clinical implications for promoting healthy aging.