Chinese team builds immune aging clock, flags RUNX1

Chinese researchers reported a Human Immune Aging Clock (HIAC) built from about 1.2 million single-cell immune profiles collected from 230 people. The study, published this week in Immunity, uses multi-omics data from peripheral blood mononuclear cells to generate a single quantitative measure of immune age by combining information across multiple immune cell types.

The clock mapped changes in immune composition and gene expression across adulthood. Analysis showed that T cell transcriptomes are the strongest predictors of immune age. The researchers found that the share of naive T cells falls with age while other T cell subtypes expand or change their gene-expression profiles. The dataset revealed an inflection point near age 40 after which immune cells remodel more rapidly and display molecular features associated with aging.

By mining the single-cell data and running functional tests, the team identified the transcription factor RUNX1 as linked to T cell youthfulness. RUNX1 levels in T cells decline with age in the dataset. Removing RUNX1 from young T cells produced molecular changes characteristic of older cells, while restoring RUNX1 in aged T cells reduced those features and made the cells resemble younger T cells. The report includes cell-based experiments and animal-model evidence supporting RUNX1’s role in modulating T cell aging.

The authors write, “Our study provides a quantitative tool for assessing immunosenescence and nominates RUNX1 as a target for rejuvenating aged immunity.” The report also notes that people whose immune profiles indicate slower immune aging tend to have higher proportions of specific T cell populations and gene-expression patterns associated with younger immune profiles.

The paper describes potential applications for HIAC in clinical research, including measuring how therapies affect immune age and grouping participants by immune health rather than chronological age. The authors say further work is needed to test RUNX1-targeted interventions in humans and to determine whether altering immune age changes overall healthspan or disease risk.