Abstract
Abstract The aging of the immune system has profound implications for individual immune responses, yet precise quantification of immune age remains a challenge. Analyzing single-cell peripheral blood mononuclear cells (PBMC) transcriptomics data from 981 healthy individuals, we developed IMMClock (IMMune Clock), a human immune age clock derived from single cell transcriptomics. IMMClock is the first to accurately assess the age of three major immune cell types, CD8+ T cells, CD4+ T cells and NK cells, at the individual level. Testing the ability of these clocks to capture the dynamic aging process, we show that they reliably predict individuals' chronological ages across seven publicly available single-cell transcriptomics datasets and the large Framingham bulk transcriptomics cohort. IMMClock identifies cell type specific age-related pathways including apoptosis, interferon gamma response, and cytokine response. The application of IMMClock reveals several associations between immune aging of different cell-types and key clinical phenotypes during aging: it recapitulates the established observation of higher immune age in males compared to females and uncovers higher immune age in CD8+ T cells of smokers and individuals with chronic illnesses including cancer. Analyzing cancer patients’ data, IMMClock readings strongly correlate with CD8+ T cell exhaustion levels, and, quite strikingly, highlights an elevated immune age in the tumor microenvironment compared to blood. Citation Format: Yael Gurevich-Schmidt, Kun Wang, Di Wu, Sanna Madan, Vishaka Gopalan, Sanju Sinha, Binbin Wang, Saugato Rahman Dhruba, Alejandro A. Schäffer, Eytan Ruppin. Cell-type-specific transcriptomic immune aging clocks reveal clinically relevant associations with chronic illnesses including cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1411.
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