Lipofuscin

Lipofuscin is the name given to fine yellow-brown pigment granules composed of lipid-containing residues of lysosomal digestion. It is considered to be one of the aging or 'wear-and-tear' pigments, found in the liver, kidney, heart muscle, retina, adrenals, nerve cells, and ganglion cells. It is specifically arranged around the nucleus, and is a type of lipochrome. Lipofuscin is the name given to fine yellow-brown pigment granules composed of lipid-containing residues of lysosomal digestion. It is considered to be one of the aging or 'wear-and-tear' pigments, found in the liver, kidney, heart muscle, retina, adrenals, nerve cells, and ganglion cells. It is specifically arranged around the nucleus, and is a type of lipochrome. It appears to be the product of the oxidation of unsaturated fatty acids and may be symptomatic of membrane damage, or damage to mitochondria and lysosomes. Aside from a large lipid content, lipofuscin is known to contain sugars and metals, including mercury, aluminium, iron, copper and zinc. Lipofuscin is also accepted as consisting of oxidized proteins (30–70%) as well as lipids (20–50%). The accumulation of lipofuscin-like material may be the result of an imbalance between formation and disposal mechanisms: Such accumulation can be induced in rats by administering a protease inhibitor (leupeptin); after a period of three months, the levels of the lipofuscin-like material return to normal, indicating the action of a significant disposal mechanism. However, this result is controversial, as it is questionable if the leupeptin-induced material is true lipofuscin. There exists evidence that 'true lipofuscin' is not degradable in vitro; whether this holds in vivo over longer time periods is not clear. The ABCR -/- knockout mouse has delayed dark adaptation but normal final rod threshold relative to controls. Bleaching the retina with strong light leads to formation of toxic cationic bis-pyridinium salt, N-retinylidene-N-retinyl-ethanolamine (A2E), which causes dry and wet age-related macular degeneration. From this experiment, it was concluded that ABCR has a significant role in preventing formation of A2E in extracellular photoreceptor surfaces during bleach recovery. Lipofuscin accumulation is a major risk factor implicated in macular degeneration, a degenerative disease of the eye, as well as Stargardt disease, an inherited juvenile form of macular degeneration. Abnormal accumulation of lipofuscin known as lipofuscinosis is associated with a family of neurodegenerative disorders – neuronal ceroid lipofuscinoses, the most common of these is Batten disease. Pathological accumulation of lipofuscin is implicated in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, certain lysosomal diseases, acromegaly, denervation atrophy, lipid myopathy, chronic obstructive pulmonary disease, and centronuclear myopathy. Accumulation of lipofuscin in the colon is the cause of the condition melanosis coli. Calorie restriction, vitamin E, and increased glutathione appear to reduce or halt the production of lipofuscin. The nootropic drug piracetam appears to significantly reduce accumulation of lipofuscin in the brain tissue of rats.