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DNA Damage Theory Of Aging
The DNA damage theory of aging proposes that aging is a consequence of unrepaired accumulation of DNA damage (naturally occurring), naturally occurring DNA damage. Damage in this context is a DNA alteration that has an abnormal structure. Although both mitochondrion, mitochondrial and Cell nucleus, nuclear DNA damage can contribute to aging, nuclear DNA is the main subject of this analysis. Nuclear DNA damage can contribute to aging either indirectly (by increasing apoptosis or Hayflick limit, cellular senescence) or directly (by increasing cell dysfunction). Several review articles have shown that deficient DNA repair, allowing greater accumulation of DNA damage, causes premature aging; and that increased DNA repair facilitates greater longevity, e.g. Mouse models of nucleotide-excision–repair syndromes reveal a striking correlation between the degree to which specific DNA repair pathways are compromised and the severity of accelerated aging, strongly suggesting a causal relation ...
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Aging
Ageing (or aging in American English) is the process of becoming Old age, older until death. The term refers mainly to humans, many other animals, and fungi; whereas for example, bacteria, perennial plants and some simple animals are potentially biologically immortal. In a broader sense, ageing can refer to single cells within an organism which have Cellular senescence, ceased dividing, or to the Population ageing, population of a species. In humans, ageing represents the accumulation of changes in a human being over time and can encompass physical, psychological, and social changes. Reaction time, for example, may slow with age, while memories and general knowledge typically increase. Of the roughly 150,000 people who die each day across the globe, about two-thirds die from age-related causes. Current Theory of aging, ageing theories are assigned to the damage concept, whereby the accumulation of damage (such as DNA oxidation) may cause biological systems to fail, or to the p ...
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Polycyclic Aromatic Hydrocarbon
A Polycyclic aromatic hydrocarbon (PAH) is any member of a class of organic compounds that is composed of multiple fused aromatic rings. Most are produced by the incomplete combustion of organic matter— by engine exhaust fumes, tobacco, incinerators, in roasted meats and cereals, or when biomass burns at lower temperatures as in forest fires. The simplest representative is naphthalene, having two aromatic rings, and the three-ring compounds anthracene and phenanthrene. PAHs are uncharged, non-polar and planar. Many are colorless. Many of them are also found in fossil fuel deposits such as coal and in petroleum. Exposure to PAHs can lead to different types of cancer, to fetal development complications, and to cardiovascular issues. Polycyclic aromatic hydrocarbons are discussed as possible starting materials for abiotic syntheses of materials required by the earliest forms of life. Nomenclature and structure The terms polyaromatic hydrocarbon, or polynuclear aromatic hydro ...
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Lamin
Lamins, also known as nuclear lamins, are fibrous proteins in Intermediate filament#Type V – nuclear lamins, type V intermediate filaments, providing structural function and Transcription (biology), transcriptional regulation in the cell nucleus. Nuclear lamins interact with inner nuclear membrane proteins to form the nuclear lamina on the interior of the nuclear envelope. Lamins have elastic and mechanosensitive properties, and can alter Regulation of gene expression, gene regulation in a feedback response to mechanical cues. Lamins are present in all animals but are not found in microorganisms, plants or Fungus, fungi. Lamin proteins are involved in the disassembling and reforming of the nuclear envelope during mitosis, the positioning of nuclear pores, and programmed cell death. Mutations in lamin genes can result in several Genetic disorder, genetic Laminopathy, laminopathies, which may be life-threatening. History Lamins were first identified in the cell nucleus, using E ...
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Base Excision Repair
Base excision repair (BER) is a cellular mechanism, studied in the fields of biochemistry and genetics, that repairs damaged DNA throughout the cell cycle. It is responsible primarily for removing small, non-helix-distorting base lesions from the genome. The related nucleotide excision repair pathway repairs bulky helix-distorting lesions. BER is important for removing damaged bases that could otherwise cause mutations by mispairing or lead to breaks in DNA during replication. BER is initiated by DNA glycosylases, which recognize and remove specific damaged or inappropriate bases, forming AP sites. These are then cleaved by an AP endonuclease. The resulting single-strand break can then be processed by either short-patch (where a single nucleotide is replaced) or long-patch BER (where 2–10 new nucleotides are synthesized). Lesions processed by BER Single bases in DNA can be chemically damaged by a variety of mechanisms, the most common ones being deamination, oxidation, ...
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Cockayne Syndrome
Cockayne syndrome (CS), also called Neill-Dingwall syndrome, is a rare and fatal autosomal recessive neurodegenerative disorder characterized by growth failure, impaired development of the nervous system, abnormal sensitivity to sunlight ( photosensitivity), eye disorders and premature aging.Bender M, Potocki L, Metry D. What syndrome is this? Cockayne syndrome. Pediatric Dermatology erial online November 2003;20(6):538-540. Available from: MEDLINE with Full Text, Ipswich, MA. Accessed April 30, 2015. Failure to thrive and neurological disorders are criteria for diagnosis, while photosensitivity, hearing loss, eye abnormalities, and cavities are other very common features. Problems with any or all of the internal organs are possible. It is associated with a group of disorders called leukodystrophies, which are conditions characterized by degradation of neurological white matter. There are two primary types of Cockayne syndrome: Cockayne syndrome type A (CSA), arising from mu ...
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Huchinson–Gilford Progeria
Progeria is a specific type of progeroid syndrome, also known as Hutchinson–Gilford syndrome or Hutchinson–Gilford progeroid syndrome (HGPS). A single gene mutation is responsible for causing progeria. The affected gene, known as lamin A (''LMNA''), makes a protein necessary for holding the cell nucleus together. When this gene mutates, an abnormal form of lamin A protein called progerin is produced. Progeroid syndromes are a group of diseases that cause individuals to age faster than usual, leading to them appearing older than they actually are. People born with progeria typically live until their mid- to late-teens or early twenties. Severe cardiovascular complications usually develop by puberty, later on resulting in death. Signs and symptoms Most children with progeria appear normal at birth and during early infancy. Children with progeria usually develop the first symptoms during their first few months of life. The earliest symptoms may include a failure to thrive an ...
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Werner Syndrome
Werner syndrome (WS) or Werner's syndrome, also known as "adult progeria",James, William; Berger, Timothy; Elston, Dirk (2005). ''Andrews' Diseases of the Skin: Clinical Dermatology''. (10th ed.). Saunders. . is a rare autosomal recessive disorder which is characterized by the appearance of premature aging. Werner syndrome is named after the German scientist Otto Werner. He identified the syndrome in four siblings observed with premature aging, which he explored as the subject of his dissertation of 1904. It has a global incidence rate of less than 1 in 100,000 live births (although incidence in Japan and Sardinia is higher, affecting 1 in 20,000–40,000 and 1 in 50,000, respectively). 1,300 cases had been reported as of 2006. Affected individuals typically grow and develop normally until puberty; the mean age of diagnosis is twenty-four, often realized when the adolescent growth spurt is not observed. The youngest person diagnosed was six years old. The median and mean ages ...
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Skeletal Striated Muscle
Skeletal muscle (commonly referred to as muscle) is one of the three types of vertebrate muscle tissue, the others being cardiac muscle and smooth muscle. They are part of the somatic nervous system, voluntary muscular system and typically are attached by tendons to bones of a skeleton. The skeletal muscle cells are much longer than in the other types of muscle tissue, and are also known as ''muscle fibers''. The tissue of a skeletal muscle is striated muscle tissue, striated – having a striped appearance due to the arrangement of the sarcomeres. A skeletal muscle contains multiple muscle fascicle, fascicles – bundles of muscle fibers. Each individual fiber and each muscle is surrounded by a type of connective tissue layer of fascia. Muscle fibers are formed from the cell fusion, fusion of developmental myoblasts in a process known as myogenesis resulting in long multinucleated cells. In these cells, the cell nucleus, nuclei, termed ''myonuclei'', are located along the inside ...
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Reactive Oxygen Species
In chemistry and biology, reactive oxygen species (ROS) are highly Reactivity (chemistry), reactive chemicals formed from diatomic oxygen (), water, and hydrogen peroxide. Some prominent ROS are hydroperoxide (H2O2), superoxide (O2−), hydroxyl radical (OH.), and singlet oxygen(1O2). ROS are pervasive because they are readily produced from O2, which is abundant. ROS are important in many ways, both beneficial and otherwise. ROS function as signals, that turn on and off biological functions. They are intermediates in the redox behavior of O2, which is central to fuel cells. ROS are central to the photodegradation of organic pollutants in the atmosphere. Most often however, ROS are discussed in a biological context, ranging from their effects on aging and their role in causing dangerous genetic mutations. Inventory of ROS ROS are not uniformly defined. All sources include superoxide, singlet oxygen, and hydroxyl radical. Hydrogen peroxide is not nearly as reactive as these s ...
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Mouse Brain
A mouse (: mice) is a small rodent. Characteristically, mice are known to have a pointed snout, small rounded ears, a body-length scaly tail, and a high breeding rate. The best known mouse species is the common house mouse (''Mus musculus''). Mice are also popular as pets. In some places, certain kinds of Apodemus, field mice are locally common. They are known to invade homes for food and shelter. Mice are typically distinguished from rats by their size. Generally, when a muroid rodent is discovered, its common name includes the term ''mouse'' if it is smaller, or ''rat'' if it is larger. The common terms ''rat'' and ''mouse'' are not Taxonomy (biology), taxonomically specific. Typical mice are classified in the genus ''Mus (genus), Mus'', but the term ''mouse'' is not confined to members of ''Mus'' and can also apply to species from other genera such as the deer mouse, deer mouse (''Peromyscus''). Fancy mouse, Domestic mice sold as pets often differ substantially in size f ...
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8-oxo-2'-deoxyguanosine
8-Oxo-2'-deoxyguanosine (8-oxo-dG) is an oxidized derivative of deoxyguanosine. 8-Oxo-dG is one of the major products of DNA oxidation. Concentrations of 8-oxo-dG within a cell are a measurement of oxidative stress. In DNA Steady-state levels of DNA damages represent the balance between formation and repair. Swenberg et al. measured average frequencies of steady state endogenous DNA damages in mammalian cells. The most frequent oxidative DNA damage normally present in DNA is 8-oxo-dG, occurring at an average frequency of 2,400 per cell. When 8-oxo-dG is induced by a DNA damaging agent it is rapidly repaired. For example, 8-oxo-dG was increased 10-fold in the livers of mice subjected to ionizing radiation, but the excess 8-oxo-dG was rapidly removed with a half-life of 11 minutes. As reviewed by Valavanidis et al. increased levels of 8-oxo-dG in a tissue can serve as a biomarker of oxidative stress. They also noted that increased levels of 8-oxo-dG are frequently found dur ...
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