HOME

TheInfoList



OR:

Collagen Collagen () is the main structural protein in the extracellular matrix found in the body's various connective tissues. As the main component of connective tissue, it is the most abundant protein in mammals, making up from 25% to 35% of the whol ...
is a protein that is an important part of
connective tissue Connective tissue is one of the four primary types of animal tissue, along with epithelial tissue, muscle tissue, and nervous tissue. It develops from the mesenchyme derived from the mesoderm the middle embryonic germ layer. Connective tiss ...
s in the body. It is a rigid, non-soluble and fibrous protein that adds up to one third of the proteins found in the human body. Collagen is mostly made up of
molecule A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and bioch ...
s that are packed together to form long and thin fibrils that support each other and ensure the skin is strong and elastic. There are various types of collagen which have individual roles and structures. Most collagen belongs to types 1, 2 and 3. Collagen consists mainly of amino acids and can be mostly found in
tendon A tendon or sinew is a tough, high-tensile-strength band of dense fibrous connective tissue that connects muscle to bone. It is able to transmit the mechanical forces of muscle contraction to the skeletal system without sacrificing its abilit ...
s, muscles,
bone A bone is a rigid organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red and white blood cells, store minerals, provide structure and support for the body, an ...
s,
skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other animal coverings, such as the arthropod exoskeleton, have different d ...
,
ligament A ligament is the fibrous connective tissue that connects bones to other bones. It is also known as ''articular ligament'', ''articular larua'', ''fibrous ligament'', or ''true ligament''. Other ligaments in the body include the: * Peritoneal ...
s and other fibrous tissues. It helps keep the skin strong and supple, and sustains the renewal of skin cells and replacement of damaged and dead body cells. The collagen tissues support the formation of bones, tendons, and cartilage that form depending on the level of mineralization. However, an individual can lose collagen components in the body due to exposure to
ultraviolet Ultraviolet (UV) is a form of electromagnetic radiation with wavelength from 10 nm (with a corresponding frequency around 30  PHz) to 400 nm (750  THz), shorter than that of visible light, but longer than X-rays. UV radiatio ...
light,
tobacco Tobacco is the common name of several plants in the genus ''Nicotiana'' of the family Solanaceae, and the general term for any product prepared from the cured leaves of these plants. More than 70 species of tobacco are known, but the chie ...
, excessive intake of sugar, and aging. This loss of collagen can cause the skin to lose elasticity, reduction of the thickness of the
epidermis The epidermis is the outermost of the three layers that comprise the skin, the inner layers being the dermis and hypodermis. The epidermis layer provides a barrier to infection from environmental pathogens and regulates the amount of water relea ...
, increase in the formation of
wrinkle A wrinkle, also known as a rhytid, is a fold, ridge or crease in an otherwise smooth surface, such as on skin or fabric. Skin wrinkles typically appear as a result of ageing processes such as glycation, habitual sleeping positions, loss of b ...
s and sagging, and also make the skin vulnerable and easily damaged.


Molecular mechanisms in Skin Aging

There are many dissimilar models that have been used to explain skin aging on a molecular basis such as the theory of cellular senescence, the reduction in the cell's
DNA repair DNA repair is a collection of processes by which a cell (biology), cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolism, metabolic activities and environmental factors such as r ...
capacity, and the loss of
telomere A telomere (; ) is a region of repetitive nucleotide sequences associated with specialized proteins at the ends of linear chromosomes. Although there are different architectures, telomeres, in a broad sense, are a widespread genetic feature mos ...
s, oxidative stress, etc. Some scientists also proposed that a large portion of skin aging is caused by external factors while only 3% is caused by internal factors. In the following sections, we discuss prominent models and advancements in molecular mechanism studies related to skin aging.


Oxidative stress

Oxidative stress Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal r ...
shows the lack of balance between the systemic appearance of the oxygen species that are reactive and the biological system's capability to detoxify the reactive elements or repairing the damage that results from the imbalance. It is known that reactive oxygen species (ROS) take part in a very crucial role in dermal changes taking place outside the cells in both aging caused by internal factors and those caused by external factors. ROS can be created from many dissimilar sources which include the
mitochondrion A mitochondrion (; ) is an organelle found in the cells of most Eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is used t ...
,
endoplasmic reticulum The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum ( ...
and peroxisomal.  In normal conditions with the exception of ligands the various actions of receptor tyrosine kinases on the surface of the cell are repressed by the receptor protein tyrosine
phosphatase In biochemistry, a phosphatase is an enzyme that uses water to cleave a phosphoric acid monoester into a phosphate ion and an alcohol. Because a phosphatase enzyme catalyzes the hydrolysis of its substrate, it is a subcategory of hydrolases. P ...
s.


DNA damage

Exposure to Ultra-violet rays may cause damage of the DNA, which may disrupt the function of genes that play a huge role in the skin stem cells
homeostasis In biology, homeostasis (British also homoeostasis) (/hɒmɪə(ʊ)ˈsteɪsɪs/) is the state of steady internal, physical, and chemical conditions maintained by living systems. This is the condition of optimal functioning for the organism and i ...
. By exposing the skin frequently to ultraviolet radiation the damage of DNA increases and mutations also take place and may result to aging prematurely or
carcinogenesis Carcinogenesis, also called oncogenesis or tumorigenesis, is the formation of a cancer, whereby normal cells are transformed into cancer cells. The process is characterized by changes at the cellular, genetic, and epigenetic levels and abnorm ...
. In a scenario where the DNA take in photons emanating from
UV-B Ultraviolet (UV) is a form of electromagnetic radiation with wavelength from 10 nm (with a corresponding frequency around 30  PHz) to 400 nm (750  THz), shorter than that of visible light, but longer than X-rays. UV radiation i ...
the nucleotides arrangement structurally changes which leads to the DNA strands having defects. In the species that are lesser, they can be able to repair the damage on the DNA using the
photolyase Photolyases () are DNA repair enzymes that repair damage caused by exposure to ultraviolet light. These enzymes require visible light (from the violet/blue end of the spectrum) both for their own activation and for the actual DNA repair. The DN ...
enzyme but higher species do not have this enzyme. Repair in the cells of humans can be attained by a
nucleotide excision repair Nucleotide excision repair is a DNA repair mechanism. DNA damage occurs constantly because of chemicals (e.g. intercalating agents), radiation and other mutagens. Three excision repair pathways exist to repair single stranded DNA damage: Nucleo ...
path, once the following proteins are deficient the skin is prone to premature aging.


Telomere shortening

Telomere A telomere (; ) is a region of repetitive nucleotide sequences associated with specialized proteins at the ends of linear chromosomes. Although there are different architectures, telomeres, in a broad sense, are a widespread genetic feature mos ...
s are
nucleoid The nucleoid (meaning '' nucleus-like'') is an irregularly shaped region within the prokaryotic cell that contains all or most of the genetic material. The chromosome of a prokaryote is circular, and its length is very large compared to the cell ...
sequences that repeat themselves and cap a chromosome. They protect the
chromosome A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins ar ...
s from dilapidation and recombination abnormality. Their length decreases with every divisions of the cell and results in cellular senescence. They are critical body structures located at the end of the eukaryotic chromosomes which consists of many copies of G rich repeats. Without the presence of Telomeres the chromosomes will combine and cause instability in the genes. The
enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. ...
that increases the telomere replications in order to prevent them from becoming short is known as telomerase. The deficiency of this enzyme can cause a hastened telomere shortening which could cause a flawed regeneration of the tissue. This also suppresses the production of epidermal cells. Also the exposure to UV is known to cause mutation of the telomere and also cause the death of the cells.


Inflammaging

This is the long-lasting
inflammation Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molec ...
that occurs as a result of aging. It affects the start and the progression of diseases that occur as a result of aging e.g. type 2 diabetes. It occurs in the skin because when exposed to the
UV radiation Ultraviolet (UV) is a form of electromagnetic radiation with wavelength from 10 nm (with a corresponding frequency around 30  PHz) to 400 nm (750  THz), shorter than that of visible light, but longer than X-rays. UV radiation i ...
it leads to the damaging of the epidermal cells which in turn cause inflammation to occur.


Collagen loss due to increase in age

When an individual ages the outermost layer of skin becomes thin despite the number of layers of the cell remaining unchanged, and the number of cells that contain a pigment reduces and the
melanocyte Melanocytes are melanin-producing neural crest-derived cells located in the bottom layer (the stratum basale) of the skin's epidermis, the middle layer of the eye (the uvea), the inner ear, vaginal epithelium, meninges, bones, and heart. M ...
s that remain increase in size. This is the reason why aging skin looks thin, pale and translucent. There may be large spots that are pigmented when some areas are exposed to sunlight. The various alterations in the connective tissue may decrease the strength of the skin and its elasticity. Also the blood vessels in the outer skin become more delicate and can result to bruises and also bleeding under the surface of the skin. The subcutaneous glands also excrete low amounts of oil as you age. The men experience this shortage mostly after reaching the age of 80 years. The women may slowly begin excreting less oil after menopause thus is very hard to keep the skin moist. The layer of subcutaneous fat also decreases thus reducing the insulation and padding capability of the skin. This can make the individual be at risk of having an injury and also finds it very hard to maintain body temperature. The sweat glands also cut down on the amount of sweat they produce thus making the individual's body harder to cool.


Lifestyle habits that lead to collagen loss


Intake too much sugar

The intake of too much sugar can lead to negative impacts to the body which include the damage of collagen. The excess consumption of sugar results to glycation that produces AGEs. This occurs naturally and when too much sugar is consumed the AGE molecules stick to the collagen molecules turning them stiff, thus damaging them. The process of
glycation Glycation (sometimes called non-enzymatic glycosylation) is the covalent attachment of a sugar to a protein or lipid. Typical sugars that participate in glycation are glucose, fructose, and their derivatives. Glycation is the non-enzymatic proc ...
not only does it damage the collagen existing in the body but also makes some alterations to its stability. When an individual intakes large amounts of sugar the process of glycation converts the collagen into an unstable type 1 which is more vulnerable and can be easily broken down thus can lead to premature aging.


Tobacco Usage

The use of tobacco can cause damage to the skin's collagen layer. It can cause the skin around the lips to lose collagen when in contact with the smoke or due to puckering of the lips around the cigarette, over time. It may also cause the vessels of blood to constrict and reduce blood flow. Due to this, perioral collagen (connective tissue around the mouth below the skin) may show signs of damage. When collagen is lost in large amounts, it may cause wrinkles to emerge. Tobacco use can also result in slow collagen healing.


Treatment for collagen loss

There are various ways in which an individual is able to treat the loss of collagen. Dietary changes may increase the turnover of the cells and increase the creation of collagen. One can also adopt exercises that stimulate the production of collagen and also increase their intake of vitamin D. Also applying the necessary amounts of sunblock can prevent harmful amounts of UV-rays from the sun causing damage to your skin. You can also protect yourself from some of the
causative In linguistics, a causative ( abbreviated ) is a valency-increasing operationPayne, Thomas E. (1997). Describing morphosyntax: A guide for field linguists'' Cambridge: Cambridge University Press. p. 173–186. that indicates that a subject either ...
s that breakdown collagen. Avoid spending too much time in the sun, apply sunblock, avoid smoking tobacco, drink plenty of water to prevent dehydration and participate in stress-relieving activities. Stress is known to cause skin aging. In order to preserve healthy, young skin there are the various things that we have to put into consideration that help to ensure this goal is achieved. Taking vitamins C and A can provide a very good boost to the production of collagen in the body. In order to maintain healthy skin, you need to nurture and protect the collagen that is existing in the body by consuming healthy foods which have the necessary Vitamins, minerals and amino acids to promote collage productions and reduce cell damage in the body.


Approaches that can be used to counter collagen loss

There are various ways which can be used to counter the loss of collagen from the body and may include the use of treatment using
vitamin A Vitamin A is a fat-soluble vitamin and an essential nutrient for humans. It is a group of organic compounds that includes retinol, retinal (also known as retinaldehyde), retinoic acid, and several provitamin A carotenoids (most notably ...
etc. The skin can be subjected to either extrinsic or intrinsic factors caused by aging. Aging skin is identified by having wrinkles, losing skin flexibility, laxity and having a rough appearance in the skin
texture Texture may refer to: Science and technology * Surface texture, the texture means smoothness, roughness, or bumpiness of the surface of an object * Texture (roads), road surface characteristics with waves shorter than road roughness * Texture ( ...
. Cutaneous aging is mostly triggered by either the intrinsic and extrinsic factors. Intrinsic aging is an unavoidable process that occurs physiologically that causes the thinning of skin, wrinkling and also slow dermal atrophy. Correspondingly, extrinsic aging is triggered and influenced by external environmental factors which may include pollution in the air, smoking, having poor nutrition and having excess exposure to the sun. In the following research we will review the various changes that take place in the process of skin aging, the advancement of research in the molecular mechanisms that lead to the changes and also the various methods of treatment and skin maintenance. Skin aging is not only affected by the intrinsic factors but also can be triggered and influenced by external factors. These changes occur simultaneously with the various phenotypic alterations in the cutaneous cells and also may change the structures and functions of extracellular constituents which may include collagens,
proteoglycan Proteoglycans are proteins that are heavily glycosylated. The basic proteoglycan unit consists of a "core protein" with one or more covalently attached glycosaminoglycan (GAG) chain(s). The point of attachment is a serine (Ser) residue to whi ...
s and elastin that are necessary for providing the strength of stretching, elasticity and the hydration of the skin. Intrinsic aging of the skin is a process of the skin changing over a period of time. Aging of the inner parts of the body that are protected mainly occur due to the intrinsic factors that can be genetic or metabolic, while the parts that are exposed are affected by the extrinsic influences, this consists mostly of ultraviolet rays from the sun. For the skin that has undergone intrinsic changes most of the variations are identifiable on the basal layer. Studies have shown that when the person becomes older the reproduction of the cells in the basal layer decreases. Thus the
epidermis The epidermis is the outermost of the three layers that comprise the skin, the inner layers being the dermis and hypodermis. The epidermis layer provides a barrier to infection from environmental pathogens and regulates the amount of water relea ...
becomes thinner and the surface area of contact in between the dermis and epidermis reduces thus leads to a decrease in the nutrition exchange to the epidermis. This causes the basal layer to be weak thus the cells cannot multiply or grow. This process which involves a decrease in the productivity of cells is known as cellular senescence. Research shows that in skin that has aged intrinsically does not only degenerate collagens, elastin etc., but also
oligosaccharide An oligosaccharide (/ˌɑlɪgoʊˈsækəˌɹaɪd/; from the Greek ὀλίγος ''olígos'', "a few", and σάκχαρ ''sácchar'', "sugar") is a saccharide polymer containing a small number (typically two to ten) of monosaccharides (simple sugar ...
which affects the skin's ability to retain moisture. Besides the internal factors that may cause skin aging, external factors such as being exposed to sunlight also causes the skin to age. 80% of the cases of skin aging have been caused by exposure to the
ultraviolet radiation Ultraviolet (UV) is a form of electromagnetic radiation with wavelength from 10 nm (with a corresponding frequency around 30  PHz) to 400 nm (750  THz), shorter than that of visible light, but longer than X-rays. UV radiatio ...
which is the primary cause of extrinsic aging of the skin. In contrast to the thinning of the epidermis in internally aged skin, the extrinsically aged skin the ultraviolet rays cause the epidermis to thicken, the outmost level of the epidermis which is the stratum corneum is affected and becomes thick due to the failure of the corneocyte
desmosome A desmosome (; "binding body"), also known as a macula adherens (plural: maculae adherentes) (Latin for ''adhering spot''), is a cell structure specialized for cell-to-cell adhesion. A type of junctional complex, they are localized spot-like adh ...
s. In the basal cells the protein on the cell surface interacts with the proteins are largely decreased showing that the rate of production of the cells is also reduced. When exposed to the ultraviolet radiation, the type VII collagen in
keratinocyte Keratinocytes are the primary type of cell found in the epidermis, the outermost layer of the skin. In humans, they constitute 90% of epidermal skin cells. Basal cells in the basal layer (''stratum basale'') of the skin are sometimes referred ...
s decreases which in turn leads to the emergence of wrinkles that come about due to weakening connection between the dermis and epidermis. Research shows that type 1 collagen reduces in amount when exposed to UV light because of the dilapidation of the collagen. There are also MMPs and proteases that take place in the dilapidation activity. In a skin that has gone through photo aging, there is a noticeable feature that occurs deeply in the dermis which is the buildup of uncharacteristic elastic tissue, this is called solar elastolysis. The UV radiation causes the level of elastin which forms the fiber cleavage which in turn causes the deposit of elastic fibers. Research has shown that aging caused by exposure to UV causes the
N-terminal The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the am ...
and center parts of the tropoelastin molecules to be prone to enzymatic cleavage thus resulting to an acceleration of the dilapidation of elastin in relation to the age of the individual. Similarly, the microvasculature also reduces as the individual ages. This occurs as a result of the
endothelial dysfunction In vascular diseases, endothelial dysfunction is a systemic pathological state of the endothelium. Along with acting as a semi-permeable membrane, the endothelium is responsible for maintaining vascular tone and regulating oxidative stress by re ...
which also comprises a reduction in angiogenic capacity and also having an impaired vasodilatory tasks.


References

{{Authority control Aging-associated diseases