Daf-2
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Daf-2
The DAF-2 gene encodes for the insulin-like growth factor 1 (IGF-1) receptor in the worm ''Caenorhabditis elegans''. DAF-2 is part of the first metabolic pathway discovered to regulate the rate of aging. DAF-2 is also known to regulate reproductive development, resistance to oxidative stress, thermotolerance, resistance to hypoxia, and resistance to bacterial pathogens. Mutations in DAF-2 have been shown by Cynthia Kenyon to double the lifespan of the worms. In a 2007 episode of WNYC’s Radiolab, Kenyon called DAF-2 "the grim reaper gene.” Long-lived mutants Long-lived ''DAF-2'' ''C. elegans'' mutants are resistant to the oxidizing agent paraquat and to UV light. ''DAF-2'' mutants also have a higher DNA repair capability than wild-type ''C. elegans''. Knockdown of the nucleotide excision repair gene ''Xpa-1'' increases sensitivity to UV and reduces the life span of the long-lived mutants. These findings support the hypothesis that DNA damage has a significant role in th ...
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Daf-16
DAF-16 is the sole ortholog of the FOXO family of transcription factors in the nematode ''Caenorhabditis elegans''. It is responsible for activating genes involved in longevity, lipogenesis, heat shock survival and oxidative stress responses. It also protects ''C.elegans'' during food deprivation, causing it to transform into a hibernation - like state, known as a Dauer. DAF-16 is notable for being the primary transcription factor required for the profound lifespan extension observed upon mutation of the insulin-like receptor ''DAF-2''. The gene has played a large role in research into longevity and the insulin signalling pathway as it is located in ''C. elegans'', a successful ageing model organism. Genetics DAF-16 is a gene conserved across species, with homologs being found in ''C. elegans'', humans, mice, and ''Drosophila'' (fruit flies). In ''C. elegans'', DAF-16 is located on Chromosome 1, at position 175-268. It is made up of 15 exons. DAF-16 is also located downstre ...
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Cynthia Kenyon
Cynthia Jane Kenyon (born February 21, 1954) is an American molecular biologist and biogerontologist known for her genetic dissection of aging in a widely used model organism, the roundworm ''Caenorhabditis elegans''. She is the vice president of aging research at Calico Research Labs, and emeritus professor of biochemistry and biophysics at the University of California, San Francisco (UCSF). Career Cynthia Kenyon graduated valedictorian in chemistry and biochemistry from the University of Georgia in 1976. She received her Ph.D. in 1981 from MIT where, in Graham Walker's laboratory, she looked for genes on the basis of their activity profiles, discovering that DNA-damaging agents activate a battery of DNA repair genes in E. coli. She then did postdoctoral studies with Nobel laureate Sydney Brenner at the MRC Laboratory of Molecular Biology in Cambridge, England, studying the development of ''C. elegans.'' Since 1986 she has been at the UCSF, where she was the Herbert Boyer Dis ...
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Gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a basic unit of heredity and the molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protein-coding genes and noncoding genes. During gene expression, the DNA is first copied into RNA. The RNA can be directly functional or be the intermediate template for a protein that performs a function. The transmission of genes to an organism's offspring is the basis of the inheritance of phenotypic traits. These genes make up different DNA sequences called genotypes. Genotypes along with environmental and developmental factors determine what the phenotypes will be. Most biological traits are under the influence of polygenes (many different genes) as well as gen ...
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Mammals
Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur or hair, and three middle ear bones. These characteristics distinguish them from reptiles (including birds) from which they diverged in the Carboniferous, over 300 million years ago. Around 6,400 extant species of mammals have been described divided into 29 orders. The largest orders, in terms of number of species, are the rodents, bats, and Eulipotyphla (hedgehogs, moles, shrews, and others). The next three are the Primates (including humans, apes, monkeys, and others), the Artiodactyla ( cetaceans and even-toed ungulates), and the Carnivora (cats, dogs, seals, and others). In terms of cladistics, which reflects evolutionary history, mammals are the only living members of the Synapsida (synapsids); this clade, together with Saur ...
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Dauer Larva
Dauer (German "''die Dauer''", English "the enduring", "the duration" in the meaning of "a length of time",) describes an alternative developmental stage of nematode worms, particularly rhabditids including '' Caenorhabditis elegans'', whereby the larva goes into a type of stasis and can survive harsh conditions. Since the entrance of the dauer stage is dependent on environmental cues, it represents a classic and well studied example of polyphenism. The dauer state is given other names in the various types of nematodes such as ‘diapause’ or ‘hypobiosis’, but since the ''C. elegans'' nematode has become the most studied nematode, the term ‘dauer stage’ or 'dauer larvae' is becoming universally recognised when referring to this state in other free-living nematodes. The dauer stage is also considered to be equivalent to the infective stage of parasitic nematode larvae. As E. Maupas first proposed in 1899-1900, all nematodes have five stages separated by four moults. Under ...
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Larva
A larva (; plural larvae ) is a distinct juvenile form many animals undergo before metamorphosis into adults. Animals with indirect development such as insects, amphibians, or cnidarians typically have a larval phase of their life cycle. The larva's appearance is generally very different from the adult form (''e.g.'' caterpillars and butterflies) including different unique structures and organs that do not occur in the adult form. Their diet may also be considerably different. Larvae are frequently adapted to different environments than adults. For example, some larvae such as tadpoles live almost exclusively in aquatic environments, but can live outside water as adult frogs. By living in a distinct environment, larvae may be given shelter from predators and reduce competition for resources with the adult population. Animals in the larval stage will consume food to fuel their transition into the adult form. In some organisms like polychaetes and barnacles, adults are immobil ...
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Eukaryotes
Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacteria and Archaea (both prokaryotes) make up the other two domains. The eukaryotes are usually now regarded as having emerged in the Archaea or as a sister of the Asgard archaea. This implies that there are only two domains of life, Bacteria and Archaea, with eukaryotes incorporated among archaea. Eukaryotes represent a small minority of the number of organisms, but, due to their generally much larger size, their collective global biomass is estimated to be about equal to that of prokaryotes. Eukaryotes emerged approximately 2.3–1.8 billion years ago, during the Proterozoic eon, likely as flagellated phagotrophs. Their name comes from the Greek εὖ (''eu'', "well" or "good") and κάρυον (''karyon'', "nut" or "kernel"). Eu ...
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Gene Knockdown
Gene knockdown is an experimental technique by which the expression of one or more of an organism's genes is reduced. The reduction can occur either through genetic modification or by treatment with a reagent such as a short DNA or RNA oligonucleotide that has a sequence complementary to either gene or an mRNA transcript. Versus transient knockdown If a DNA of an organism is genetically modified, the resulting organism is called a "knockdown organism." If the change in gene expression is caused by an oligonucleotide binding to an mRNA or temporarily binding to a gene, this leads to a temporary change in gene expression that does not modify the chromosomal DNA, and the result is referred to as a "transient knockdown". In a transient knockdown, the binding of this oligonucleotide to the active gene or its transcripts causes decreased expression through a variety of processes. Binding can occur either through the blocking of transcription (in the case of gene-binding), the degradati ...
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Antioxidants
Antioxidants are compounds that inhibit oxidation, a chemical reaction that can produce free radicals. This can lead to polymerization and other chain reactions. They are frequently added to industrial products, such as fuels and lubricants, to prevent oxidation, and to foods to prevent spoilage, in particular the rancidification of oils and fats. In cells, antioxidants such as glutathione, mycothiol or bacillithiol, and enzyme systems like superoxide dismutase, can prevent damage from oxidative stress. The only dietary antioxidants are vitamins A, C, and E, but the term ''antioxidant'' has also been applied to numerous other dietary compounds that only have antioxidant properties in vitro, with little evidence for antioxidant properties in vivo. Dietary supplements marketed as antioxidants have not been shown to maintain health or prevent disease in humans. History As part of their adaptation from marine life, terrestrial plants began producing non-marine antioxi ...
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Heat Shock Protein
Heat shock proteins (HSP) are a family of proteins produced by cells in response to exposure to stressful conditions. They were first described in relation to heat shock, but are now known to also be expressed during other stresses including exposure to cold, UV light and during wound healing or tissue remodeling. Many members of this group perform chaperone functions by stabilizing new proteins to ensure correct folding or by helping to refold proteins that were damaged by the cell stress. This increase in expression is transcriptionally regulated. The dramatic upregulation of the heat shock proteins is a key part of the heat shock response and is induced primarily by heat shock factor (HSF). HSPs are found in virtually all living organisms, from bacteria to humans. Heat-shock proteins are named according to their molecular weight. For example, HSP60, Hsp60, Hsp70 and Hsp90 (the most widely studied HSPs) refer to families of heat shock proteins on the order of 60, 70 and 90 ato ...
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Transcription (genetics)
Transcription is the process of copying a segment of DNA into RNA. The segments of DNA transcribed into RNA molecules that can encode proteins are said to produce messenger RNA (mRNA). Other segments of DNA are copied into RNA molecules called non-coding RNAs (ncRNAs). mRNA comprises only 1–3% of total RNA samples. Less than 2% of the human genome can be transcribed into mRNA ( Human genome#Coding vs. noncoding DNA), while at least 80% of mammalian genomic DNA can be actively transcribed (in one or more types of cells), with the majority of this 80% considered to be ncRNA. Both DNA and RNA are nucleic acids, which use base pairs of nucleotides as a complementary language. During transcription, a DNA sequence is read by an RNA polymerase, which produces a complementary, antiparallel RNA strand called a primary transcript. Transcription proceeds in the following general steps: # RNA polymerase, together with one or more general transcription factors, binds to promoter DNA ...
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Cell Nucleus
The cell nucleus (pl. nuclei; from Latin or , meaning ''kernel'' or ''seed'') is a membrane-bound organelle found in eukaryotic cells. Eukaryotic cells usually have a single nucleus, but a few cell types, such as mammalian red blood cells, have no nuclei, and a few others including osteoclasts have many. The main structures making up the nucleus are the nuclear envelope, a double membrane that encloses the entire organelle and isolates its contents from the cellular cytoplasm; and the nuclear matrix, a network within the nucleus that adds mechanical support. The cell nucleus contains nearly all of the cell's genome. Nuclear DNA is often organized into multiple chromosomes – long stands of DNA dotted with various proteins, such as histones, that protect and organize the DNA. The genes within these chromosomes are structured in such a way to promote cell function. The nucleus maintains the integrity of genes and controls the activities of the cell by regulating gene expres ...
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