Journal: Nature aging
This study investigates the mechanisms of age-related thymic involution and its effects on peripheral T cells using single-cell sequencing of nearly 388,000 cells from human thymus and blood samples across different ages.
Aging was found to:
- Reduce T-lineage potential in early thymic progenitors
- Increase innate lymphocyte lineage potential
The aged thymus showed:
- Decline in thymic epithelial cells and tissue-restricted antigen expression
- Accumulation of mature T cells with low SOX4 and inflammatory profiles
In peripheral blood, distinct transcriptional changes correlated with T cell aging, enabling the development of a naive T cell-based immune age prediction model.
CD38 was identified as a marker for recent thymic emigrants.
Additionally, T cell receptor repertoire analysis revealed:
- Reduced diversity
- Expansion of virus-specific T cells in older individuals
These findings deepen understanding of thymic involution and peripheral T cell aging, suggesting potential targets to restore immune function in older adults.