Aging Changes the Heart's Response to Injury
Older people are less capable of regeneration from injury. On top of that, the heart is one of the least regenerative organs in the body, vulnerable in ways that other muscle tissue is not. Cardiovascular disease leads to heart injury, and the aged body is much less able to compensate than would be the case in a younger individual. These are problems in search of solutions. Even in a world in which the case of cardiovascular disease, the growth of atherosclerotic lesions in blood vessels, is prevented, one would still want to be able to reverse the loss of tissue maintenance and regenerative capacity of the heart.
In contrast to neonates and lower organisms, the adult mammalian heart lacks any capacity to regenerate following injury. The vast majority of our understanding of cardiac regeneration is based on research in young animals. Research in aged individuals is rare. This is unfortunate as aging induces many changes in the heart. As the heart ages, the capacity of the organ to respond to increased workload decreases. The stress this entails promotes diastolic dysfunction, arrhythmias, and heart failure. These changes to the normal function of the heart ensure that young and aged adults respond differently to cardiac injury.
In young adults, cardiac injury initially induces an inflammatory response whereby neutrophils, M1 macrophages, T-cells, and B-cells invade the injury area to remove dead cells and initiate the reparative phase. The reparative phase is associated with a shift in immune cell populations which actively resolve inflammation and induce fibroblasts to secrete fibrous tissue proteins. The latter results in a stable scar. In contrast, the inflammatory response in older hearts following injury is muted; resulting in delayed clearance of dead cells. Moreover, fibroblast responses to fibrotic cues are markedly weaker. Fibrous protein production is dampened, leading to weaker and less stable scars. Weaker scars affect cardiac function by increasing systolic dysfunction and dilative remodeling. Dampened immune and fibroblast responses in aged individuals lowers the capacity to respond to stressors.