Human PBMC scRNA-seq–based aging clocks reveal ribosome to inflammation balance as a single-cell aging hallmark and super longevity
Hongming Zhu, Jiawei Chen, Kangping Liu, Lei Gao, Haiyan Wu, Liangliang Ma, Jieru Zhou, Zhongmin Liu, Jing‐Dong J. Han
Abstract
Quantifying aging rate is important for evaluating age-associated decline and mortality. A blood single-cell RNA sequencing dataset for seven supercentenarians (SCs) was recently generated. Here, we generate a reference 28-sample aging cohort to compute a single-cell level aging clock and to determine the biological age of SCs. Our clock model placed the SCs at a blood biological age to between 80.43 and 102.67 years. Compared to the model-expected aging trajectory, SCs display increased naive CD8 + T cells, decreased cytotoxic CD8 + T cells, memory CD4 + T cells, and megakaryocytes. As the most prominent molecular hallmarks at the single-cell level, SCs contain more cells and cell types with high ribosome level, which is associated with and, according to Bayesian network inference, contributes to a low inflammation state and slow aging of SCs. Inhibiting ribosomal activity or translation in monocytes validates such translation against inflammation balance revealed by our single-cell aging clock.