lipofuscin

Lipofuscin is a pigment granule that accumulates in cells with age. It is yellow-brown and autofluorescent, commonly described as an aging pigment, and is found within lysosomes of postmitotic cells such as neurons, cardiac myocytes, and retinal pigment epithelium.

It consists of cross-linked proteins, lipids, and other bisretinoid and oxidized adducts. Lipofuscin forms from the incomplete degradation of damaged cellular material within lysosomes, arising from lipid peroxidation and oxidative damage. The material is resistant to lysosomal proteolysis and lipases, leading to the formation of insoluble granules.

Lipofuscin accumulates progressively with age in many tissues, with higher levels in long-lived cells. In the brain and heart, levels tend to rise during aging. In the retina, lipofuscin accumulates in the retinal pigment epithelium as lipid-rich granules, reflecting sustained photoreceptor turnover and lysosomal processing.

The pigment is autofluorescent, emitting broad-spectrum fluorescence when excited by blue light. This property allows lipofuscin to be detected and quantified in histology and imaging, where it serves as a marker of cellular aging and stress.

In the retina, a notable component is A2E (N-retinylidene-N-retinylethanolamine), a bisretinoid formed from all-trans-retinal and phosphatidylethanolamine. A2E and related compounds contribute to light-induced toxicity and lysosomal dysfunction, linking lipofuscin to age-related macular degeneration and Stargardt disease.

Clinically, lipofuscin is considered a biomarker of cellular aging. Excessive buildup can interfere with lysosomal function and promote oxidative stress, though it is not generally regarded as the sole cause of aging. Research seeks ways to enhance lysosomal clearance and reduce formation.