Researchers here look at the detailed impact of aging on the extracellular matrix of heart tissue. The extracellular matrix supports cells and its configuration and composition determines the physical properties of tissue. There are many issues that arise with aging in this structure, one of the most important of which is the cross-linking of matrix molecules by metabolic byproducts that are a challenge for the body to remove. Cross-links produce a reduction in tissue elasticity, among other changes, and in cardiovascular tissues this leads to hypertension, remodeling of the heart, and ultimately heart disease and death. Another important age-related issue in the extracellular matrix, one with the same ultimate outcome, is the growth of fibrosis. In this case the structure of the extracellular matrix is disrupted by the formation of scar tissue, something that occurs due to the progressive dysfunction of regenerative processes.
Age-related changes in cardiac homeostasis can be observed at the cellular, extracellular, and tissue levels. Progressive cardiomyocyte hypertrophy, inflammation, and the gradual development of cardiac fibrosis are hallmarks of cardiac aging. In the absence of a secondary insult such as hypertension, these changes are subtle and result in slight to moderate impaired myocardial function, particularly diastolic function. While collagen deposition and cross-linking increase during aging, extracellular matrix (ECM) degradation capacity also increases due to increased expression of matrix metalloproteinases (MMPs).
Of the MMPs elevated with cardiac aging, a number of studies have assessed MMP-9 in cardiac aging. There is strong evidence that MMP-9 is a major mediator for increased stiffness in the aging heart. In addition to proteolytic activity on ECM components, MMPs oversee cell signaling during the aging process by modulating cytokine, chemokine, growth factor, hormone, and angiogenic factor expression and activity. In association with elevated MMP-9, macrophage numbers increase in an age-dependent manner to regulate the ECM and angiogenic responses. Understanding the complexity of the molecular interactions between MMPs and the ECM in the context of aging may provide novel diagnostic indicators for the early detection of age-related fibrosis and cardiac dysfunction. One possible direction is to better understand how MMP activities could be modified to prevent or slow the development of excessive cardiomyocyte hypertrophy and ECM deposition. Aging is a resetting of baseline values to set a new homeostasis, and attempts to delay or prevent this shift may improve the cardiac aging phenotype.