Volume 120, October 2025, 105922Author links open overlay panel, , , , , , , , , , , , , , , SummaryBackground

Centenarians are considered as an optimal population for studying healthy ageing. However, immune features associated with super longevity have only been investigated in a few small studies using a single research method.

Methods

In this study, single-cell RNA sequencing (scRNA-seq), mass cytometry, and flow cytometry analysis were used to analyse the immune feature of peripheral blood mononuclear cells (PBMCs) from 17 centenarians (CENs), 9 of their offsprings (COs), and 14 of their offsprings’ spouses or neighbours (controls, CTs) from Lingao County of China. scRNA-seq data from the other two cohorts were downloaded from public databases.

Findings

Comprehensive analysis of 31 CENs, 17 COs, and 26 CTs from these three cohorts revealed decreased percentages of B cells and CD4+ T cells and an increased percentage of natural killer (NK) cells in PBMCs from CENs, compared with CTs. Moreover, NK cells from CENs exhibited relatively “young” signatures, including cell subset distribution and key membrane receptor expression. Enhanced RUNX3 expression in NK cells was observed in CENs, with reinforced interactions between NK and T cells, which promoted T cell function by modulating MHC-I, CD99 and MIF signalling.

Interpretation

CENs exhibit unique immunological features, especially NK cells with young protein expression signatures and immune functions.

FundingThis study was funded by the Sanya Science and Technology Innovation Special Project (No. 2022KJCX02), National Natural Science Foundation of China (No. 32141005, 82270769), Specific Research Fund of the Innovation Platform for Academicians of Hainan Province, and National Key Research and Development Program of China (Nos. 2022YFC3602900, 2022YFC3602902, 2022YFC3602903).Keywords

Centenarians

PBMCs

Single-cell RNA sequencing

Mass cytometry

Immune remodelling

© 2025 The Author(s). Published by Elsevier B.V.