The ageing holobiont: crosstalk between telomere dynamics, oxidative stress and the gut microbiome.

The gut tissue is at the frontline of early onset of ageing. It exhibits high cell turnover rates and rapid telomere shortening, which can have systemic effects on the developing or senescing organism. We conducted a literature review of studies on the crosstalk between telomere length dynamics, telomerase activity, oxidative stress, and gut microbiota composition and activity in animals. Studies mainly on humans and animal models include correlations between telomere dynamics and gut microbiome components, particularly under pathogenic conditions, but also manipulations of either the gut microbiome through faecal microbiota transplantations or of telomere dynamics using telomerase knockout models. This synthesis reveals that components of the gut microbiome including microbial metabolites and pathogenic bacteria can affect telomere dynamics through oxidative-stress-inducing processes, and that telomere maintenance is critical in maintaining gut barrier and tissue integrity, which link inflammation and gut dysbiosis. Some of the interactions between the gut microbiome and host telomere dynamics are bidirectional and important in maintaining intestinal homeostasis. However, many of the causal molecular or cellular mechanisms - and how they translate into organismal senescence - remain to be identified. Furthermore, we highlight how recent advances in whole genome sequencing capacities and bioinformatic tools represent an often-unexploited resource for measuring telomere lengths and may be particularly valuable tools within the hologenomic framework outlined here. Investigating the role of telomere dynamics in mediating gut microbiota-host interactions in different species will improve our understanding of how crosstalk between these hallmarks of ageing shape holobiont physiology in general and the ageing phenotype in particular.