Grant: Summer Program in Aging

People can age well and maintain good health for most of late life, or age poorly, developing various illnesses as they age. This 'unhealthy aging' is defined by a condition called frailty. The gut changes with age and we believe this affects how well it functions. As well as in digestion, the gut has a huge role in health through interactions with the rest of the body. Therefore, we believe when the gut does not work properly, it has a harmful effect on whole-body health. However, it is unclear whether changes in the gut contribute to frailty. These changes affect the gut's ability to act as a barrier to the body. Therefore, the gut becomes 'leakier' with age, and nutrients and bacteria may enter the body in the wrong way. In this way, leaky guts can cause inflammation, which worsens the effects of frailty. We have found, in mice, that gut barrier function worsens with age and frailty and differs by sex. We hypothesize that the gut becomes leakier and increases inflammation with both age and frailty, with females having leakier guts than males. By looking at 31 measures of health, such as physical health and behaviour, we score frailty in our mice. We will measure the amounts of proteins in the gut associated with maintaining its structure, such as tight junction proteins. We will also use microscopy techniques to visualize the locations and structure of mucins (proteins that form a protective mucus barrier). We will investigate the effect of gut leakiness on inflammation by testing the blood for inflammatory markers. Results will be categorized by age, frailty, and sex. We expect gut leakiness and inflammation will increase with age and frailty and be greater in female mice. To our knowledge, this is the first investigation into the different impacts of age and frailty on the gut while also looking at sex-dependent changes. Our findings may help identify targets for new treatments that prevent gut leakiness and inflammation to prolong the health of older adults.