Intervention against autodigestion enhances cardiovascular stability and trauma response in the elder

Abstract An important step to improve the quality of life in older adults is to reduce their heightened sensitivity to trauma challenges, such as elective surgery. Our recent evidence indicates that a mechanism behind aging and reduced quality of life involves the leakage of pancreatic digestive enzymes from the gastrointestinal tract into the bloodstream and peripheral organs. The leaked enzymes degrade plasma proteins, extracellular matrix proteins, and membrane receptors, leading to cell and organ dysfunctions typical for aging. Here, we hypothesize that blockade of leaked digestive enzymes improves the quality of life in the elderly and their response to trauma. A one-week oral treatment of old rats with a pancreatic digestive serine protease (trypsin) inhibitor, without significantly impairing normal digestion, decreases protease activity in the central circulation and benefits older individuals facing trauma. We find that this pretreatment stabilizes the cardiovascular system of aged rats, improves metabolic disturbances caused by hemorrhagic shock, and significantly enhances their response to shock. Systolic and mean arterial blood pressures are normalized, and the baroreflex, which is severely impaired in aged rats, is substantially improved by the pretreatment. The survival rate during central blood pressure reduction is significantly higher in old rats pretreated against trypsin activity. The evidence confirms our hypothesis that aging results from the uncontrolled activity of digestive enzymes outside the pancreas and intestine, and that blocking their activity improves the ability of aged rats to withstand cardiovascular challenges. The proposed intervention protocol against the degrative action of digestive enzymes is clinically applicable and testable.