Single-cell transcriptomics reveal intrinsic and systemic T cell aging in COVID-19 and HIV

Area of Science:

• Immunology
• Genomics
• Aging Research

Background:

• Current aging biomarkers often rely on bulk cell measurements, obscuring cell-intrinsic aging from systemic effects.
• Distinguishing between cellular composition shifts and intrinsic cellular aging is crucial for understanding disease impacts.

Purpose of the Study:

• To develop and apply a single-cell transcriptomic clock to differentiate systemic and cell-intrinsic aging.
• To investigate immune aging signatures in response to COVID-19 and HIV+ART.

Main Methods:

• Utilized single-cell RNA sequencing to analyze aging at cellular and bulk levels.
• Developed 'Tictock' (T immune cell transcriptomic clock) for age and cell type prediction in T cells.
• Performed Gene Ontology enrichment analysis on shared clock genes.

Main Results:

• Tictock accurately predicts age and cell type across six human T cell subsets.
• COVID-19 associated with increased CD8+ cytotoxic T cells; HIV+ART showed stable T cell composition.
• Both COVID-19 and HIV+ART increased transcriptomic age in naïve CD8+ T cells.
• Identified common aging pathways including ribosomal components and TNF receptor binding.

Conclusions:

• Single-cell transcriptomic biomarkers can disentangle systemic and cell-intrinsic immune aging.
• This approach offers a powerful tool for measuring immune aging in health and disease.
• Findings highlight distinct immune aging profiles in COVID-19 and HIV+ART.