Impact of frailty on cardiac function in health and disease in aging mice: a model for therapeutic interventions to treat frailty

As anyone who has ever attended their high school reunion knows, people age at different rates. Because a person's actual age is not always the same as their biological age, some older adults are fit and others are frail. Frailty is a major health care problem, because frail people are often harmed by traditional medical care. For example, even though fit people in their nineties can benefit greatly from cardiovascular surgery, more than half of frail older adults either die or end up in long-term care after such surgeries. Even so, we know very little about frailty and its effects on organs like the heart, in part because we have not had an animal model to investigate frailty and its potential treatment. Our research group has just discovered how to measure frailty in aging mice. We measured many different health problems in individual mice and used this information to estimate a frailty index score. We found that individual heart cells become very large in frail animals. However, the ability of these large cells to contract declines, which would reduce the force of the heartbeat. This suggests that frailty is associated with harmful changes in heart cells that may make the heart more susceptible to heart diseases. The goal of the current research project is to understand how frailty affects the heart's ability to function under normal conditions and during times when blood flow to the heart is reduced. As part of this study, we will look at how frailty develops over time in mice and we will compare our results to what is known about frailty in people. We will also give older mice a drug that may help treat frailty and we will explore how this treatment works. This research project is important because it will help us understand the links between frailty and heart disease. This study will also develop a new way to test treatments for frailty in older people.