Investigating the role of age-associated intestinal barrier dysfunction in driving T cell ageing

  • Jessica Conway (Speaker)

Activity: Academic and Industrial eventsConference, workshop or symposium


Advancing age is accompanied by impaired intestinal barrier function, resulting in increased permeability and systemic passage of microbial products. Additionally, ageing is accompanied by shrinkage (involution) of the thymus and alterations in tissue architecture and microenvironment, contributing towards a decline in naïve T cell output. Other features of T cell ageing include the accumulation of memory and senescent T cells, Th17 polarisation and an increase in regulatory T cells. However, whether there are any links between gut barrier dysfunction and T cell ageing remains unknown.

To elucidate this, we assessed circulating markers of intestinal barrier dysfunction (occludin) in 55 healthy older adults. Participants were split into two groups: old adults with low microbial translocation (MT) (n=24) and old adults with high MT (n=31).

Our results revealed that older adults with high MT displayed a greater proportion of memory, senescent and regulatory T cells but fewer recent thymic emigrants compared to those with low MT. Furthermore, high MT participants exhibited impaired autophagy and DNA damage repair, both hallmarks of immune ageing. Intestinal barrier disruption levels were also negatively associated with the immunological age (IMM-AGE) of participants. Lastly, we identified a potential causal relationship between age-related gut barrier dysfunction and thymic involution using an aged germ-free mouse model.

Together, these findings provide the evidence base for investigating the potential of intestinal barrier-targeted therapies to combat T cell ageing and promote healthy ageing.
PeriodOct 2022
Degree of RecognitionNational