Aging, exercise, and sex: impact on the pathophysiology of ventilation-induced lung injury

Relevance: Our research focuses on a disease called Acute Respiratory Distress Syndrome (ARDS) in which the lung has difficulty getting oxygen into the blood, and that can be caused by lung infections, such as COVID-19. Approximately 30-40% of people with ARDS will die of the disease. Importantly, one of the key treatments for ARDS is mechanical ventilation, which is a treatment to help people breathe by pushing air into the lungs. However, mechanical ventilation can also cause more injury to the lungs. Problem to be addressed: To study ARDS and the damage caused by mechanical ventilation, we and many other laboratories use animals. Although great progress has been made, a problem with previous studies has been the standard practice of using young male animals for the experiments, even though in humans the disease occurs in both males and females and mostly within the older population. To overcome this limitation, we will investigate mechanical ventilation in older animals of both sexes that better reflect the human population. Experimental plan: For our studies, we will use aged male and female mice to study the development of lung injury. For example, we will utilize 22-month-old mice, which is comparable to a 65-year-old human, and study how the lungs of these animals respond to damage by mechanical ventilation. We will also examine the effects of exercise (running on a treadmill), since studies have demonstrated that regular exercise can protect against respiratory disease. Further, we will investigate various cellular pathways and molecules in the lung that are known to be important in ARDS. Impact: The novelty of our study is that we take a "real life" approach to scientific laboratory studies. With a better understanding of actual population-based issues that impact the development and/or the severity of ARDS, we will be better equipped to develop strategies to improve outcomes associated with this disease.