Lipofuscin is the name given to finely granular yellow brown pigment granules composed of lipid-containing residues of lysosomal digestion. For the drug referred to as "pigment" see Black tar heroin. In cell biology, a granule can be any structure barely visible by light microscopy Lipids are broadly defined as any fat- Soluble ( lipophilic) naturally-occurring Molecule, such as fats oils waxes cholesterol sterols fat-soluble Lysosomes are Organelles that contain Digestive enzymes (acid Hydrolases. 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. The liver is a vital organ in the human body and is present in Vertebrates and some other animals The kidneys are complicated organs that have numerous biological roles The heart is a muscular organ in all Vertebrates responsible for pumping Blood through the Blood vessels by repeated rhythmic In Mammals the adrenal glands (also known as suprarenal glands) are the triangle-shaped Endocrine glands that sit on top of the Kidneys their A nerve is an enclosed cable-like bundle of peripheral Axons (the long slender projections of Neurons. In Anatomy, a ganglion (pl ganglia) is a tissue mass. Neurology In neurological contexts ganglia are composed mainly of 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. The dermis is a layer of Skin beneath the epidermis that consists of Connective tissue, and cushions the body from stress and strain
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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. In Chemistry, especially Biochemistry, a fatty acid is a Carboxylic acid often with a long unbranched Aliphatic tail ( chain) which In Cell biology, a mitochondrion (plural mitochondria) is a membrane-enclosed Organelle found in most eukaryotic cells. Lysosomes are Organelles that contain Digestive enzymes (acid Hydrolases. Aside from a large lipid content, lipofuscin is known to contain sugars and metals, including mercury, aluminum, iron, copper and zinc. Mercury (ˈmɜrkjʊri also called quicksilver or hydrargyrum, is a Chemical element with the symbol Hg ( Latinized hydrargyrum WikipediaNaming Iron (ˈаɪɚn is a Chemical element with the symbol Fe (ferrum and Atomic number 26 Copper (ˈkɒpɚ is a Chemical element with the symbol Cu (cuprum and Atomic number 29 Zinc (ˈzɪŋk from Zink is a Metallic Chemical element with the symbol Zn and Atomic number 30 [1]
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; after a period of three months, the levels of the lipofuscin-like material return to normal, indicating the action of a significant disposal mechanism. A protease is any Enzyme that conducts Proteolysis, that is begins protein Catabolism by Hydrolysis of the Peptide bonds that link [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 a major risk factor implicated in macular degeneration, a degenerative disease of the eye. Macular degeneration is a medical condition usually of older adults which results in a loss of vision in the center of the visual field (the Macula) because [8]
Abnormal accumulation of lipofuscin is associated with a group of diseases of neurodegenerative disorder type called lipofuscinoses, e. A disease is an abnormal condition of an organism that impairs bodily functions and can be deadly Neurodegenerative Disease ( Greek νέυρο- néuro-, "nerval" and Latin dēgenerāre, "to decline" or "to Neuronal Ceroid Lipofuscinoses ( NCL) is the general name for a Family of at least eight genetically separate Neurodegenerative disorders that result from g. , neuronal ceroid lipofuscinosis, also known as Batten disease, as well as some other names. Neuronal Ceroid Lipofuscinoses ( NCL) is the general name for a Family of at least eight genetically separate Neurodegenerative disorders that result from Batten disease is a rare fatal Autosomal recessive Neurodegenerative disorder that begins in childhood
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. Alzheimer's disease ( AD) also called Alzheimer disease or simply Alzheimer's, is the most common form of Dementia. Parkinson's disease (also known as Parkinson disease or PD) is a degenerative disorder of the Central nervous system that often impairs the sufferer's The lysosomal storage diseases are a group of over forty human Genetic disorders that result from defects in lysosomal function Acromegaly (from Greek akros "extreme" or "extremities" and megalos "large" - extremities enlargement is a Syndrome Chronic obstructive pulmonary disease ( COPD) is a Disease of the lungs in which the Airways become narrowed Centronuclear myopathies (CNM are a group of Congenital Myopathies where cell nuclei are abnormally located in skeletal muscle cells
Accumulation of lipofuscin in the colon is the cause of the condition melanosis coli. Melanosis coli is a disorder of pigmentation of the wall of the colon, identified at the time of Colonoscopy.
Possible treatments
A calorie restricted diet appears to reduce or halt the production of lipofuscin. Calorie restriction, or caloric restriction (CR aims to improve health and slow the aging process by limiting dietary energy intake [1]
Vitamin E appears to reduce or halt the formation of lipofuscin. See also Tocopherol, Tocotrienol Vitamin E is the collective name for a set of 8 related Tocopherols and Tocotrienols which are fat-soluble [1] Increased glutathione production also appears to retard accumulation of lipofuscin. Glutathione ( GSH) is a Tripeptide. It contains an unusual Peptide linkage between the amine group of Cysteine and the Carboxyl [1]
The nootropic drug piracetam appears to significantly reduce accumulation of lipofuscin in the brain tissue of rats. '''Nootropics''' popularly referred to as " smart drugs " " smart nutrients " " cognitive enhancers " and " brain enhancers Piracetam (brand name Nootropil, Qropi, Myocalm, Dinagen) is a Nootropic. [10]
References
- ^ a b c d Chris Gaugler, "Lipofuscin", Stanislaus Journal of Biochemical Reviews May 1997
- ^ 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.
- ^ Alexei Terman and Ulf T. Brunk, "Is Lipofuscin Eliminated from Cells?", Investigative Ophthalmology and Visual Science, (1999) vol. 40 pp. 2463-2464.
- ^ Sallyanne Davies and Steven Ellis, "Lipofuscin Turnover", Investigative Ophthalmology and Visual Science. (1999)40 pp. 1887-1888
- ^ 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
- ^ 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
- ^ 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
- ^ John Lacey, "Harvard Medical signs agreement with Merck to develop potential therapy for macular degeneration", 23-May-2006
- ^ Muscle Nerve (2002) vol 25 pp. 383-389
- ^ 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. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 15147719.
- Histology at neuro.wustl.edu
- Histology at BU 20301loa
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