![Lipofuscin neuro](https://upload.wikimedia.org/wikipedia/commons/5/5e/Lipofuscin_neuro.jpg)
Lipofuscin is the name given to fine yellow-brown
pigment
A pigment is a colored material that is completely or nearly insoluble in water. In contrast, dyes are typically soluble, at least at some stage in their use. Generally dyes are often organic compounds whereas pigments are often inorganic compo ...
granules composed of
lipid
Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include ...
-containing residues of
lysosomal
A lysosome () is a membrane-bound organelle found in many animal Cell (biology), cells. They are spherical Vesicle (biology and chemistry), vesicles that contain Hydrolysis, hydrolytic enzymes that can break down many kinds of biomolecules. A ly ...
digestion.
It is considered to be one of the aging or "wear-and-tear" pigments, found in the
liver
The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...
,
kidney
The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...
,
heart
The heart is a muscular organ in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as carbon dioxide t ...
muscle, retina,
adrenal
The adrenal glands (also known as suprarenal glands) are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys. Each gland has an outer cortex which ...
s,
nerve
A nerve is an enclosed, cable-like bundle of nerve fibers (called axons) in the peripheral nervous system.
A nerve transmits electrical impulses. It is the basic unit of the peripheral nervous system. A nerve provides a common pathway for the e ...
cells, and
ganglion
A ganglion is a group of neuron cell bodies in the peripheral nervous system. In the somatic nervous system this includes dorsal root ganglia and trigeminal ganglia among a few others. In the autonomic nervous system there are both sympatheti ...
cells.
Formation and turnover
Lipofuscin appears to be the product of the
oxidation
Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a d ...
of
unsaturated fatty acid
In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, f ...
s and may be symptomatic of membrane damage, or damage to
mitochondria
A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...
and
lysosome
A lysosome () is a membrane-bound organelle found in many animal cells. They are spherical vesicles that contain hydrolytic enzymes that can break down many kinds of biomolecules. A lysosome has a specific composition, of both its membrane prot ...
s. Aside from a large lipid content, lipofuscin is known to contain sugars and metals, including
mercury
Mercury commonly refers to:
* Mercury (planet), the nearest planet to the Sun
* Mercury (element), a metallic chemical element with the symbol Hg
* Mercury (mythology), a Roman god
Mercury or The Mercury may also refer to:
Companies
* Merc ...
,
aluminium
Aluminium (aluminum in American and Canadian English) is a chemical element with the symbol Al and atomic number 13. Aluminium has a density lower than those of other common metals, at approximately one third that of steel. I ...
,
iron
Iron () is a chemical element with symbol Fe (from la, ferrum) and atomic number 26. It is a metal that belongs to the first transition series and group 8 of the periodic table. It is, by mass, the most common element on Earth, right in f ...
,
copper
Copper is a chemical element with the symbol Cu (from la, cuprum) and atomic number 29. It is a soft, malleable, and ductile metal with very high thermal and electrical conductivity. A freshly exposed surface of pure copper has a pinkis ...
and
zinc
Zinc is a chemical element with the symbol Zn and atomic number 30. Zinc is a slightly brittle metal at room temperature and has a shiny-greyish appearance when oxidation is removed. It is the first element in group 12 (IIB) of the periodi ...
.
[Chris Gaugler,]
Lipofuscin
", ''Stanislaus Journal of Biochemical Reviews'' May 1997 Lipofuscin is also accepted as consisting of oxidized proteins (30–70%) as well as lipids (20–50%).
It is a type of
lipochrome and is specifically arranged around the nucleus.
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
A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes (increases reaction rate or "speeds up") proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the ...
inhibitor (
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.
It is often used during ''in vitro'' experiments when a specific enzymati ...
); 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, 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.
It is often used during ''in vitro'' experiments when a specific enzymati ...
-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
Macular degeneration, also known as age-related macular degeneration (AMD or ARMD), is a medical condition which may result in blurred or no vision in the center of the visual field. Early on there are often no symptoms. Over time, however, som ...
.
From this experiment, it was concluded that ABCR has a significant role in preventing formation of A2E in extracellular photoreceptor surfaces during bleach recovery.
Relation to diseases
![Cardiac myocyte showing lipofuscin pigment](https://upload.wikimedia.org/wikipedia/commons/5/56/Cardiac_myocyte_showing_lipofuscin_pigment.jpg)
Lipofuscin accumulation in the eye, is a major risk factor implicated in
macular degeneration
Macular degeneration, also known as age-related macular degeneration (AMD or ARMD), is a medical condition which may result in blurred or no vision in the center of the visual field. Early on there are often no symptoms. Over time, however, som ...
, a degenerative disease, and
Stargardt disease
Stargardt disease is the most common inherited single-gene retinal disease. In terms of the first description of the disease, it follows an autosomal recessive inheritance pattern, which has been later linked to bi-allelic ABCA4 gene variants (S ...
, an inherited juvenile form of macular degeneration.
In the
peripheral nervous system
The peripheral nervous system (PNS) is one of two components that make up the nervous system of bilateral animals, with the other part being the central nervous system (CNS). The PNS consists of nerves and ganglia, which lie outside the brain ...
, abnormal accumulation of lipofuscin known as ''lipofuscinosis''
is associated with a family of
neurodegenerative disorder
A neurodegenerative disease is caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration. Such neuronal damage may ultimately involve cell death. Neurodegenerative diseases include amyotrophic ...
s –
neuronal ceroid lipofuscinoses
Neuronal ceroid lipofuscinosis is the general name for a family of at least eight genetically separate neurodegenerative lysosomal storage diseases that result from excessive accumulation of lipopigments (lipofuscin) in the body's tissues. These l ...
, the most common of these is
Batten disease
Batten disease is a fatal disease of the nervous system that typically begins in childhood. Onset of symptoms is usually between 5 and 10 years of age. Often, it is autosomal recessive. It is the common name for a group of disorders called the n ...
.
Also, pathological accumulation of lipofuscin is implicated in
Alzheimer's disease
Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...
,
Parkinson's disease
Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...
,
amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or Lou Gehrig's disease, is a neurodegenerative disease that results in the progressive loss of motor neurons that control voluntary muscles. ALS is the most comm ...
, certain
lysosomal diseases,
acromegaly
Acromegaly is a disorder that results from excess growth hormone (GH) after the growth plates have closed. The initial symptom is typically enlargement of the hands and feet. There may also be an enlargement of the forehead, jaw, and nose. Other ...
, denervation
atrophy
Atrophy is the partial or complete wasting away of a part of the body. Causes of atrophy include mutations (which can destroy the gene to build up the organ), poor nourishment, poor circulation, loss of hormonal support, loss of nerve supply t ...
,
lipid
Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include ...
myopathy
In medicine, myopathy is a disease of the muscle in which the muscle fibers do not function properly. This results in muscular weakness. ''Myopathy'' means muscle disease (Greek : myo- ''muscle'' + patheia '' -pathy'' : ''suffering''). This meani ...
,
chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease (COPD) is a type of progressive lung disease characterized by long-term respiratory symptoms and airflow limitation. The main symptoms include shortness of breath and a cough, which may or may not produce ...
, and
centronuclear myopathy. Accumulation of lipofuscin in the colon is the cause of the condition
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. The brown pigment is lipofuscin in ...
.
On the other hand,
myocardial lipofuscin accumulation more directly reflects chronological ageing rather than human cardiac pathology.
Possible therapies
Calorie restriction
Calorie restriction (caloric restriction or energy restriction) is a dietary regimen that reduces intake of energy from caloric foods & beverages without incurring malnutrition. "Reduce" can be defined relative to the subject's previous intake be ...
,
vitamin E
Vitamin E is a group of eight fat soluble compounds that include four tocopherols and four tocotrienols. Vitamin E deficiency, which is rare and usually due to an underlying problem with digesting dietary fat rather than from a diet low in vitami ...
,
and increased
glutathione appear to reduce or halt the production of lipofuscin.
The
nootropic drug piracetam
Piracetam is a drug marketed as a treatment for myoclonus. It is also used as a cognitive enhancer to improve memory, attention, and learning. Evidence to support its use is unclear, with some studies showing modest benefits in specific populat ...
appears to significantly reduce accumulation of lipofuscin in the brain tissue of rats.
Other possible treatments:
*
Centrophenoxine
Meclofenoxate (INN, BAN; brand name Lucidril, also known as centrophenoxine) is a cholinergic nootropic used as a dietary supplement. It is an ester of dimethylethanolamine (DMAE) and 4-chlorophenoxyacetic acid (pCPA).
In elderly patients, me ...
*
Acetyl-L-carnitine
Acetyl-L-carnitine, ALCAR or ALC, is an acetylated form of L-carnitine. It is naturally produced by the human body, and it is available as a dietary supplement. Acetylcarnitine is broken down in the blood by plasma esterases to carnitine which is ...
*''
Ginkgo biloba
''Ginkgo biloba'', commonly known as ginkgo or gingko ( ), also known as the maidenhair tree, is a species of tree native to China. It is the last living species in the order Ginkgoales, which first appeared over 290 million years ago. Fossils ...
''
*
Dimethylethanolamine
*
Curcumin
Wet
macular degeneration
Macular degeneration, also known as age-related macular degeneration (AMD or ARMD), is a medical condition which may result in blurred or no vision in the center of the visual field. Early on there are often no symptoms. Over time, however, som ...
can be treated using selective
photothermolysis
Laser hair removal is the process of hair removal by means of exposure to pulses of laser light that destroy the hair follicle. It had been performed experimentally for about twenty years before becoming commercially available in 1995 and 1996. ...
where a pulsed unfocused
laser
A laser is a device that emits light through a process of optical amplification based on the stimulated emission of electromagnetic radiation. The word "laser" is an acronym for "light amplification by stimulated emission of radiation". The fir ...
predominantly heats and kills 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
A tattoo is a form of body modification made by inserting tattoo ink, dyes, and/or pigments, either indelible or temporary, into the dermis layer of the skin to form a design. Tattoo artists create these designs using several tattooing pr ...
,
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
Life extension is the concept of extending the human lifespan, either modestly through improvements in medicine or dramatically by increasing the maximum lifespan beyond its generally-settled limit of 125 years.
Several researchers in the are ...
.
Soraprazan (remofuscin) has been found to remove lipofuscin from retinal pigment epithelial cells in animals. This opens up a new therapy option for the treatment of dry age-related macular degeneration and
Stargardt disease
Stargardt disease is the most common inherited single-gene retinal disease. In terms of the first description of the disease, it follows an autosomal recessive inheritance pattern, which has been later linked to bi-allelic ABCA4 gene variants (S ...
, for which there is currently no treatment. The drug has now been granted
orphan drug
An orphan drug is a pharmaceutical agent developed to treat medical conditions which, because they are so rare, would not be profitable to produce without government assistance. The conditions are referred to as orphan diseases.
The assignment of ...
designation for the treatment of Stargardt disease by the European Medicines Agency.
Other uses
Lipofuscin quantification is used for age determination in various
crustacean
Crustaceans (Crustacea, ) form a large, diverse arthropod taxon which includes such animals as decapods, seed shrimp, branchiopods, fish lice, krill, remipedes, isopods, barnacles, copepods, amphipods and mantis shrimp. The crustacean group ...
s such as
lobster
Lobsters are a family (biology), family (Nephropidae, Synonym (taxonomy), synonym Homaridae) of marine crustaceans. They have long bodies with muscular tails and live in crevices or burrows on the sea floor. Three of their five pairs of legs ...
s and
spiny 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 crustaceans 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.
See also
*
Residual body In lysosomal digestion, residual bodies are vesicles containing indigestible materials. Residual bodies are either secreted by the cell via exocytosis (this generally only occurs in macrophages), or they become lipofuscin granules that remain in ...
*
Advanced glycation end-products (AGEs)
References
20. Young B, Lowe JS, Stevens A, Heath JW. Wheater's Functional Histology: A Text and Atlas. 6th ed. Elsevier
External links for general reviews
*
Histology at neuro.wustl.edu*
Destroying Lipofuscin and Destroying Cancer, FightAging.orgUnfocused Pulsed Lasers Selectively Destroy Lipofuscin, AcceleratingFuture.com
{{Pathology
Biomolecules
Senescence