Lipofuscin
Encyclopedia
Pigment
A pigment is a material that changes the color of reflected or transmitted light as the result of wavelength-selective absorption. This physical process differs from fluorescence, phosphorescence, and other forms of luminescence, in which a material emits light.Many materials selectively absorb...
granules
Granule (cell biology)
In cell biology, a granule is a small particle. It can be any structure barely visible by light microscopy. The term is most often used to describe a secretory vesicle.-Leukocytes:...
composed of lipid
Lipid
Lipids constitute a broad group of naturally occurring molecules that include fats, waxes, sterols, fat-soluble vitamins , monoglycerides, diglycerides, triglycerides, phospholipids, and others...
-containing residues of lysosomal digestion. It is considered one of the aging or "wear-and-tear" pigments, found in the liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
, kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
, heart
Heart
The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...
muscle, adrenals, nerve
Nerve
A peripheral nerve, or simply nerve, is an enclosed, cable-like bundle of peripheral axons . A nerve provides a common pathway for the electrochemical nerve impulses that are transmitted along each of the axons. Nerves are found only in the peripheral nervous system...
cells, and ganglion
Ganglion
In anatomy, a ganglion is a biological tissue mass, most commonly a mass of nerve cell bodies. Cells found in a ganglion are called ganglion cells, though this term is also sometimes used to refer specifically to retinal ganglion cells....
cells. It is specifically arranged around the nucleus, and is a type of Lipochrome
Lipochrome
Lipochrome is a form of pigment associated with amber and gold tones in human eyes and the eyes of other mammals.The term carotenoid is sometimes considered a synonym, but that term usually refers to specific molecules, while lipochrome refers to accumulations of varied molecules....
.
Formation and turnover
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 lysosomeLysosome
thumb|350px|Schematic of typical animal cell, showing subcellular components. [[Organelle]]s: [[nucleoli]] [[cell nucleus|nucleus]] [[ribosomes]] [[vesicle |vesicle]] rough [[endoplasmic reticulum]]...
s. Aside from a large lipid content, lipofuscin is known to contain sugars and metals, including mercury
Mercury (element)
Mercury is a chemical element with the symbol Hg and atomic number 80. It is also known as quicksilver or hydrargyrum...
, aluminum, iron
Iron
Iron is a chemical element with the symbol Fe and atomic number 26. It is a metal in the first transition series. It is the most common element forming the planet Earth as a whole, forming much of Earth's outer and inner core. It is the fourth most common element in the Earth's crust...
, copper
Copper
Copper is a chemical element with the symbol Cu and atomic number 29. It is a ductile metal with very high thermal and electrical conductivity. Pure copper is soft and malleable; an exposed surface has a reddish-orange tarnish...
and zinc
Zinc
Zinc , or spelter , is a metallic chemical element; it has the symbol Zn and atomic number 30. It is the first element in group 12 of the periodic table. Zinc is, in some respects, chemically similar to magnesium, because its ion is of similar size and its only common oxidation state is +2...
.
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
Protease
A protease is any enzyme that conducts proteolysis, that is, begins protein catabolism by hydrolysis of the peptide bonds that link amino acids together in the polypeptide chain forming the protein....
inhibitor (leupeptin
Leupeptin
Leupeptin, also known as N-acetyl-L-leucyl-L-leucyl-L-argininal, is a naturally occurring protease inhibitor that can inhibit cysteine, serine and threonine peptidases....
); 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
Leupeptin
Leupeptin, also known as N-acetyl-L-leucyl-L-leucyl-L-argininal, is a naturally occurring protease inhibitor that can inhibit cysteine, serine and threonine peptidases....
-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.
Relation to diseases
Lipofuscin accumulation is a major risk factor implicated in macular degenerationMacular degeneration
Age-related macular degeneration is a medical condition which usually affects older adults and results in a loss of vision in the center of the visual field because of damage to the retina. It occurs in “dry” and “wet” forms. It is a major cause of blindness and visual impairment in older adults...
, a degenerative disease of the eye.
Abnormal accumulation of lipofuscin is associated with a group of disease
Disease
A disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs. It may be caused by external factors, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune...
s of neurodegenerative disorder type called lipofuscinoses, e.g., neuronal ceroid lipofuscinosis
Neuronal Ceroid Lipofuscinosis
Neuronal Ceroid Lipofuscinoses is the general name for a family of at least eight genetically separate neurodegenerative disorders that result from excessive accumulation of lipopigments in the body's tissues. These lipopigments are made up of fats and proteins...
, also known as Batten disease
Batten disease
Batten disease is a rare, fatal autosomal recessive neurodegenerative disorder that begins in childhood...
, as well as some other names.
Pathological accumulation of lipofuscin is implicated in Alzheimer's disease
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
, Parkinson's disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...
, amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis , also referred to as Lou Gehrig's disease, is a form of motor neuron disease caused by the degeneration of upper and lower neurons, located in the ventral horn of the spinal cord and the cortical neurons that provide their efferent input...
, certain lysosomal diseases, acromegaly
Acromegaly
Acromegaly is a syndrome that results when the anterior pituitary gland produces excess growth hormone after epiphyseal plate closure at puberty...
, denervation atrophy
Atrophy
Atrophy is the partial or complete wasting away of a part of the body. Causes of atrophy include mutations , poor nourishment, poor circulation, loss of hormonal support, loss of nerve supply to the target organ, disuse or lack of exercise or disease intrinsic to the tissue itself...
, lipid
Lipid
Lipids constitute a broad group of naturally occurring molecules that include fats, waxes, sterols, fat-soluble vitamins , monoglycerides, diglycerides, triglycerides, phospholipids, and others...
myopathy
Myopathy
In medicine, a myopathy is a muscular disease in which the muscle fibers do not function for any one of many reasons, resulting in muscular weakness. "Myopathy" simply means muscle disease...
, chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease , also known as chronic obstructive lung disease , chronic obstructive airway disease , chronic airflow limitation and chronic obstructive respiratory disease , is the co-occurrence of chronic bronchitis and emphysema, a pair of commonly co-existing diseases...
, centronuclear myopathy
Centronuclear myopathy
Centronuclear myopathies are a group of congenital myopathies where cell nuclei are abnormally located in skeletal muscle cells. In CNM the nuclei are located at a position in the center of the cell, instead of their normal location at the periphery....
.
Accumulation of lipofuscin in the colon is the cause of the condition melanosis coli
Melanosis coli
Melanosis coli, also pseudomelanosis coli, is a disorder of pigmentation of the wall of the colon, often identified at the time of colonoscopy. It is benign, and may have no significant correlation with disease...
.
Possible therapies to reduce lipofuscin accumulation
Calorie restriction, vitamin EVitamin E
Vitamin E is used to refer to a group of fat-soluble compounds that include both tocopherols and tocotrienols. There are many different forms of vitamin E, of which γ-tocopherol is the most common in the North American diet. γ-Tocopherol can be found in corn oil, soybean oil, margarine and dressings...
,, and increased glutathione
Glutathione
Glutathione is a tripeptide that contains an unusual peptide linkage between the amine group of cysteine and the carboxyl group of the glutamate side-chain...
appear to reduce or halt the production of lipofuscin.
The nootropic drug piracetam
Piracetam
Piracetam is a nootropic drug. Piracetam's chemical name is 2-oxo-1-pyrrolidine acetamide; it shares the same 2-oxo-pyrrolidone base structure with 2-oxo-pyrrolidine carboxylic acid . Piracetam is a cyclic derivative of GABA. It is one of the group of racetams...
appears to significantly reduce accumulation of lipofuscin in the brain tissue of rats.
Other possible treatments:
- CentrophenoxineCentrophenoxineMeclofenoxate , also known as centrophenoxine, is a drug used to treat the symptoms of senile dementia and Alzheimer's disease. It is an ester of dimethylethanolamine and 4-chlorophenoxyacetic acid . DMAE is a natural substance, found especially in fish...
- Acetyl-L-Carnitine
- Ginko Biloba
- DMAE http://www.dmae.org/herbal-remedies/dmae/DMAE-benefits
Wet macular degeneration
Macular degeneration
Age-related macular degeneration is a medical condition which usually affects older adults and results in a loss of vision in the center of the visual field because of damage to the retina. It occurs in “dry” and “wet” forms. It is a major cause of blindness and visual impairment in older adults...
can be treated using Selective Photothermolysis where a pulsed unfocused laser
Laser
A laser is a device that emits light through a process of optical amplification based on the stimulated emission of photons. The term "laser" originated as an acronym for Light Amplification by Stimulated Emission of Radiation...
prodominantly heats and kills pigment- (i.e.: lipofuscin-) rich cells, leaving untouched healthy cells to multiply and fill in the gaps. The technique is also used as a skin treatment to remove tattoos
Tattoo removal
Tattoo removal has been performed with various tools during the history of tattooing. While tattoos were once considered permanent, it is now possible to remove them with treatments, fully or partially...
, liverspots, and in general make skin appear younger. This ability to selectively target lipofuscin has opened up research opportunities in the field of Anti-aging medicine.
Other uses of lipofuscin
An interesting application of lipofuscin quantification is in age determination in various crustacea such as lobsters. Since these animals lack bony parts, they cannot be aged in the same way as bony fish, in which annual increments in the ear-bones or otoliths are commonly used. Age determination of fish and shellfish is a fundamental step in generating basic biological data such as growth curves, and is needed for many stock assessment methods. Several studies have indicated that quantifying the amount of lipofuscin present in the eye-stalks of various crutacea can give an index of their age. This method has not yet been widely applied in fisheries management mainly due to problems in relating lipofuscin levels in wild-caught animals with accumulation curves derived from aquarium-reared animals.External links for general reviews
- Chris Gaugler, "Lipofuscin", Stanislaus Journal of Biochemical Reviews May 1997
- Histology at neuro.wustl.edu
- Destroying Lipofuscin and Destroying Cancer, FightAging.org
- Unfocused Pulsed Lasers Selectively Destroy Lipofuscin, AcceleratingFuture.com