Single-Cell Profiling Reveals Distinct Immune Communication Networks in Centenarians and Elderly Controls
Liwei Qiu1, Chen Dong1, Rui Zhao1
1Research Center of Clinical Medicine, Research Center of Gerontology and Longevity, Research Center of Immunology, Department of Rheumatology, Department of Geriatrics, Affiliated Hospital of Nantong University, Nantong University, Nantong, China.
None:
Aberrant cell-cell communication (CCC) is a recognized hallmark of aging, yet comprehensive analyses of immune CCC-particularly in the context of healthy aging-remain limited. Using single-cell transcriptomics of PBMCs from centenarians (CEN), their offspring (CO), and elderly controls, we found that immune CCC in controls was characterized by myeloid-derived, self-amplifying SASP signals associated with immunosenescence and effector immune cell (EIC) exhaustion. In contrast, healthy-aging individuals (CEN/CO) exhibited reinforced positive regulatory factor (PRF)-mediated ligand-receptor (LR) interactions, such as IL-15 and IL-18, consistent with enhanced EIC cytotoxicity and immune surveillance. These findings were further supported in an independent longevity cohort. Our results suggest distinct immune CCC reprogramming with age and identify a characteristic immune remodeling pattern in centenarians, providing a framework for understanding healthy aging and exceptional longevity.
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