Cellular accumulation of lipofuscin in the heart: implications in health and disease

Lipofuscin is a subcellular pigmented granule that has long been considered a sign of wear-and-tear and aging. This granule cannot be degraded but may be diluted by cell division. In the heart, lipofuscin can be easily identified in cardiomyocytes where proliferative capacity is limited, and to a lesser extent in other cardiac cell types, by their characteristic morphological features. They appear as yellow-brown granules in histopathology sections reflecting their lipid origins, and as heterogenous membrane-bound bodies containing a mix of lipid and electron-lucent content in transmission electron microscopy. Lipofuscin was originally considered a mere byproduct of age-related cell senescence but studies over the past three decades have indicated that its role and mechanism of formation may be far more complex. In this review, we examine how lipofuscin is formed and its implications in aging and diseases of the heart. While the focus of this review is on lipofuscin in the two most predominate cell types of the heart, cardiomyocytes and fibroblasts, we also touch on the presence of lipofuscin in the vasculature in certain disease phenotypes that are directly relevant to cardiovascular health.