Klotho (biology)
Encyclopedia
Klotho is an enzyme
that in humans is encoded by the KL
gene
.
This gene encodes a type-I membrane protein that is related to β-glucuronidases. Reduced production of this protein has been observed in patients with chronic renal failure (CRF), and this may be one of the factors underlying the degenerative processes (e.g., arteriosclerosis, osteoporosis, and skin atrophy) seen in CRF. Also, mutations within this protein have been associated with ageing and bone loss. Transgenic mice that overexpress Klotho live longer than wild-type mice.
that, in addition to other effects, provides some control over the sensitivity of the organism to insulin
and appears to be involved in aging. Its discovery was documented in 1997 by Kuro-o et al. The name of the gene comes from Klotho or Clotho
, one of the Moirae
, or Fates, in Greek mythology
.
The Klotho protein is a novel β-glucuronidase (EC number
3.2.1.31) capable of hydrolyzing steroid
β-glucuronides
. Genetic variants in KLOTHO have been associated with human aging, and Klotho protein has been shown to be a circulating factor detectable in serum
that declines with age.
Klotho-deficient mice manifest a syndrome
resembling accelerated human aging and display extensive and accelerated arteriosclerosis
. Additionally, they exhibit impaired endothelium
dependent vasodilation
and impaired angiogenesis
, suggesting that Klotho protein may protect the cardiovascular system through endothelium-derived NO
production.
Although the vast majority of research has been based on lack of Klotho, it was demonstrated that an overexpression of Klotho in mice
might extend their average life span between 19% and 31% compared to normal mice. However, the actual use of overexpressing Klotho for extending life-span without side-effects is still a matter of speculation and remains to be justified by further experimentation.
Klotho-deficient mice show increased production of vitamin D, and altered mineral-ion homeostasis is suggested to be a cause of premature aging–like phenotypes, because the lowering of vitamin D activity by dietary restriction reverses the premature aging–like phenotypes and prolongs survival in these mutants. These results suggest that aging–like phenotypes were due to klotho-associated vitamin D metabolic abnormalities (hypervitaminosis).
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
that in humans is encoded by the KL
KL
- Abbreviation :KL is a two letter initialism that may stand for:* Kalaallisut language , a language of the Inuit of Greenland* Kenny Loggins, a soft rock music singer* Kiloliter, a type of unit measurement for volume...
gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
This gene encodes a type-I membrane protein that is related to β-glucuronidases. Reduced production of this protein has been observed in patients with chronic renal failure (CRF), and this may be one of the factors underlying the degenerative processes (e.g., arteriosclerosis, osteoporosis, and skin atrophy) seen in CRF. Also, mutations within this protein have been associated with ageing and bone loss. Transgenic mice that overexpress Klotho live longer than wild-type mice.
Function
Klotho is a transmembrane proteinTransmembrane protein
A transmembrane protein is a protein that goes from one side of a membrane through to the other side of the membrane. Many TPs function as gateways or "loading docks" to deny or permit the transport of specific substances across the biological membrane, to get into the cell, or out of the cell as...
that, in addition to other effects, provides some control over the sensitivity of the organism to insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
and appears to be involved in aging. Its discovery was documented in 1997 by Kuro-o et al. The name of the gene comes from Klotho or Clotho
Clotho
Clotho is one of the Three Fates or Moirae, in ancient Greek mythology. Her Roman equivalent is Nona. Clotho was responsible for spinning the thread of human life. She also made major decisions, such as when a person was born, thus in effect controlling people's lives...
, one of the Moirae
Moirae
The Moirae, Moerae or Moirai , in Greek mythology, were the white-robed incarnations of destiny . Their number became fixed at three...
, or Fates, in Greek mythology
Greek mythology
Greek mythology is the body of myths and legends belonging to the ancient Greeks, concerning their gods and heroes, the nature of the world, and the origins and significance of their own cult and ritual practices. They were a part of religion in ancient Greece...
.
The Klotho protein is a novel β-glucuronidase (EC number
EC number
The Enzyme Commission number is a numerical classification scheme for enzymes, based on the chemical reactions they catalyze....
3.2.1.31) capable of hydrolyzing steroid
Steroid
A steroid is a type of organic compound that contains a characteristic arrangement of four cycloalkane rings that are joined to each other. Examples of steroids include the dietary fat cholesterol, the sex hormones estradiol and testosterone, and the anti-inflammatory drug dexamethasone.The core...
β-glucuronides
Glucuronide
A glucuronide, also known as glucuronoside, is any substance produced by linking glucuronic acid to another substance via a glycosidic bond...
. Genetic variants in KLOTHO have been associated with human aging, and Klotho protein has been shown to be a circulating factor detectable in serum
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
that declines with age.
Klotho-deficient mice manifest a syndrome
Syndrome
In medicine and psychology, a syndrome is the association of several clinically recognizable features, signs , symptoms , phenomena or characteristics that often occur together, so that the presence of one or more features alerts the physician to the possible presence of the others...
resembling accelerated human aging and display extensive and accelerated arteriosclerosis
Arteriosclerosis
Arteriosclerosis refers to a stiffening of arteries.Arteriosclerosis is a general term describing any hardening of medium or large arteries It should not be confused with "arteriolosclerosis" or "atherosclerosis".Also known by the name "myoconditis" which is...
. Additionally, they exhibit impaired endothelium
Endothelium
The endothelium is the thin layer of cells that lines the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. These cells are called endothelial cells. Endothelial cells line the entire circulatory system, from the heart...
dependent vasodilation
Vasodilation
Vasodilation refers to the widening of blood vessels resulting from relaxation of smooth muscle cells within the vessel walls, particularly in the large arteries, smaller arterioles and large veins. The process is essentially the opposite of vasoconstriction, or the narrowing of blood vessels. When...
and impaired angiogenesis
Angiogenesis
Angiogenesis is the physiological process involving the growth of new blood vessels from pre-existing vessels. Though there has been some debate over terminology, vasculogenesis is the term used for spontaneous blood-vessel formation, and intussusception is the term for the formation of new blood...
, suggesting that Klotho protein may protect the cardiovascular system through endothelium-derived NO
Nitric oxide
Nitric oxide, also known as nitrogen monoxide, is a diatomic molecule with chemical formula NO. It is a free radical and is an important intermediate in the chemical industry...
production.
Although the vast majority of research has been based on lack of Klotho, it was demonstrated that an overexpression of Klotho in mice
House mouse
The house mouse is a small rodent, a mouse, one of the most numerous species of the genus Mus.As a wild animal the house mouse mainly lives associated with humans, causing damage to crops and stored food....
might extend their average life span between 19% and 31% compared to normal mice. However, the actual use of overexpressing Klotho for extending life-span without side-effects is still a matter of speculation and remains to be justified by further experimentation.
Klotho-deficient mice show increased production of vitamin D, and altered mineral-ion homeostasis is suggested to be a cause of premature aging–like phenotypes, because the lowering of vitamin D activity by dietary restriction reverses the premature aging–like phenotypes and prolongs survival in these mutants. These results suggest that aging–like phenotypes were due to klotho-associated vitamin D metabolic abnormalities (hypervitaminosis).