Immune and microbiota contributions to age-related intestinal decline

Abstract

Deterioration of the innate immune system is generally accepted as a hallmark of aging. As a consequence of immune dysregulation, the host is not able to reliably fight infection or retain a symbiotic relationship with gut microbes. Individuals diagnosed with immune-related pathologies demonstrate gut microbial imbalances, or dysbiosis, as well as a decline in immune cell function. Additionally, aging significantly contributes to immune cell decline. Studies in adult Drosophila melanogaster have reported age-related dysbiosis as a primary driver of immune dysfunction. The objective of this thesis is to better understand how specific physiological changes, namely microbial imbalance, and immune dysfunction, along the aging intestine affect gut and host health. Here, my data demonstrates that the consequences of chronic immune activation, in particular microbial imbalance and changes in immune cell number and function, are closely associated with immune-induced intestinal permeability. This adds weight to recently published work across multiple model organisms that highlights the key role of intestinal barrier loss as a driver of age-related decline. Detailed insight into the immune factors that drive intestinal barrier loss and how this drives age-associated decline in immune function, for example, changes in macrophages, could lead to the development of immune-targeted antiaging therapies.