Lipofuscin

Lipofuscin is the name given to finely granular yellow brown pigment granules composed of lipid-containing residues of lysosomal digestion. It is considered one of the aging or "wear and tear" pigments; found in the liver, kidney, heart muscle, adrenals, nerve cells, and ganglion cells. It is specifically arranged around the nucleus. It does not affect normal cellular morphology and function. "Liver spots" commonly associated with aging are superficial dermal lipofuscin deposits.

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Formation and turnover

It appears to be the product of the peroxidation 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, aluminum, iron, copper and zinc.^[1]

The accumulation of lipofuscin-like material may be the result of an imbalance between formation and disposal mechanisms: accumulation can be induced in rats by administering a protease inhibitor; after a period of three months, the levels of the lipofuscin-like material return to normal, indicating the action of a significant disposal mechanism. ^[2] However, this result is controversial, as it is questionable if the leupeptin-induced material is true lipofuscin.^[3][4] There exists evidence that "true lipofuscin" is not degradable in vitro^[5][6][7]; whether this holds in vivo over longer time periods is not clear.

Relation to diseases

Lipofuscin accumulation is major risk factor implicated in macular degeneration, a degenerative disease of the eye.^[8]

Abnormal accumulation of lipofuscin is associated with a group of diseases of neurodegenerative disorder type called lipofuscinoses, e.g., neuronal ceroid lipofuscinosis, also known as Batten disease, as well as some other names.

Pathological accumulation of lipofuscin is implicated in Alzheimer's disease, Parkinson's disease, certain lysosomal diseases, acromegaly, denervation atrophy, lipid myopathy, chronic obstructive pulmonary disease^[9], centronuclear myopathy.

Possible treatments

A calorie restricted diet appears to reduce or halt the production of lipofuscin.^[1]

Vitamin E appears to reduce or halt the formation of lipofuscin.^[1] Increased glutathione production also appears to retard accumulation of lipofuscin.^[1]

The nootropic drug piracetam appears to significantly reduce accumulation of lipofuscin in the brain tissue of rats. ^[10]

References

1. ^ ^{a b c d} Chris Gaugler, "Lipofuscin", Stanislaus Journal of Biochemical Reviews May 1997
2. ^ ML Katz, LM Rice and CL Gao, "Reversible accumulation of lipofuscin-like inclusions in the retinal pigment epithelium", Investigative Ophthalmology & Visual Science, Vol 40,(1999) pp.175-181.
3. ^ Alexei Terman and Ulf T. Brunk, "Is Lipofuscin Eliminated from Cells?", Investigative Ophthalmology and Visual Science, (1999) vol. 40 pp.2463-2464.
4. ^ Sallyanne Davies and Steven Ellis, "Lipofuscin Turnover", Investigative Ophthalmology and Visual Science. (1999)40 pp.1887-1888
5. ^ Terman, A, Brunk, UT (1998) "On the degradability and exocytosis of ceroid/lipofuscin in cultured rat cardiac myocytes", Mech Ageing Dev 100, pp.145-156
6. ^ Terman, A, Brunk, UT (1998) "Ceroid/lipofuscin formation in cultured human fibroblasts: the role of oxidative stress and lysosomal proteolysis", Mech Ageing Dev 104, pp.277-291
7. ^ Elleder, M, Drahota, Z, Lisa, V, et al (1995) "Tissue culture loading test with storage granules from animal models of neuronal ceroid-lipofuscinosis (Batten disease): testing their lysosomal degradability by normal and Batten cells" Am J Med Genet 57, pp.213-221
8. ^ John Lacey, "Harvard Medical signs agreement with Merck to develop potential therapy for macular degeneration", 23-May-2006
9. ^ Muscle Nerve (2002) vol 25 pp.383-389
10. ^ Paula-Barbosa, M. et al, "The effects of Piracetam on lipofuscin of the rat cerebellar and hippocampa; neurons after long-term alcohol treatment and withdrawal", Alcoholism: Clinical and Experimental Research 15, (1991) pp. 834-838.

General reviews

• Chris Gaugler, "Lipofuscin", Stanislaus Journal of Biochemical Reviews May 1997
• Terman A, Brunk U (2004). "Lipofuscin.". Int J Biochem Cell Biol 36 (8): 1400-4. PMID 15147719.
• Histology at neuro.wustl.edu
• Histology at BU 20301loa