Biology subjects

Tomusiak, A.

Publications and source records attributed to Tomusiak, A..

2 recordsLinked to original sources

bioRxiv2024

Utilizing blood single-cell transcriptomics to integrate intrinsic and systemic immune aging

Biomarkers of aging provide insight into the biological effects of interventions and diseases. However, most biomarkers today are based on measurements derived from bulk cell measurements, making it challenging to interpret whether an effect is due to changes in cell type composition (systemic factors) or a cell intrinsic effect. Single-cell RNA sequencing provides a unique platform to simultaneously compare aging-associated changes on both a cellular and bulk level. We first generated a single-cell combined automated human blood cell type and age predictor (clock) for six distinct human T cell subsets. We applied these tools to find acute COVID is associated with a shift in CD8+ cytotoxic cell proportions, while cell type proportions are stable in patients with HIV on long-term ART treatment (HIV+ART). Both COVID and HIV+ART were associated with an increase in naive CD8 T cell transcriptomic age. We further found our single-cell aging biomarker is linked to ribosomal gene expression and has a link to mean cellular transcript length. This study highlights the potential of single cell transcriptomic biomarkers for understanding how the human immune system is impacted by age-associated systemic changes in cell type composition and intrinsic cellular aging.

immunology↗

bioRxiv2023

Development of a novel epigenetic clock resistant to changes in immune cell composition

Epigenetic clocks are age predictors that use machine-learning models trained on DNA CpG methylation values to predict chronological or biological age. Increases in predicted epigenetic age relative to chronological age (epigenetic age acceleration) are connected to aging-associated pathologies, and changes in epigenetic age are linked to canonical aging hallmarks. However, epigenetic clocks rely on training data from bulk tissues whose cellular composition changes with age. We found that human naive CD8+ T cells, which decrease during aging, exhibit an epigenetic age 15-20 years younger than effector memory CD8+ T cells from the same individual. Importantly, homogenous naive T cells isolated from individuals of different ages show a progressive increase in epigenetic age, indicating that current epigenetic clocks measure two independent variables, aging and immune cell composition. To isolate the age-associated cell intrinsic changes, we created a new clock, the IntrinClock, that did not change among 10 immune cell types tested. IntrinClock showed a robust predicted epigenetic age increase in a model of replicative senescence in vitro and age reversal during OSKM-mediated reprogramming.

genomics↗