The Genetics of Aging
DNA Repair Genes 2
A Table of the so far identified
Human DNA Repair Genes
A Table of the so far identified
Human DNA Repair Genes
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Cockayne syndrome; Needed for transcription-coupled NER |
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Transcription and NER |
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Accessory factor for transcription and recombination, E3 Ubiquitin ligase |
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A structure-specific DNA nuclease |
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XRCC4-LIG4 interacting factor |
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p53-inducible ribonucleotide reductase small subunit 2 homolog |
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DNA crosslink repair? |
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3' exonuclease |
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incision 3' of hypoxanthine and uracil |
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Genes defective in diseases associated with sensitivity to DNA damaging agents |
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Involved in tolerance or repair of DNA crosslinks |
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Xp22.31 |
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DNA helicase and possible nuclease in the XPF-Hef-Mus81 family |
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DNA crosslink repair |
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Related to SNM1 |
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Similar to RPA2 |
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Similar to RAD52 |
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ATR-interacting protein |
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Genes Associated with Aging
‘A great deal of genes are involved in the process of aging’
The above statement might seem simplistic, but it is essentially true. A large number of genes play a role in modulating the metabolic processes which are involved in the eventual degradation of DNA and cellular structures. Some of these genes are involved with the processes of DNA repair, some with managing the levels of free radicals and some with regulating the speed of metabolism itself. Together the varying rates at which these genes are expressed, results in an overall affect of the longevity of the organism itself.
Below is a list of the currently confirmed genes that have been associated through experimentation with cellular longevity. They all have there own mechanisms of action and several of them will be discussed in detail in this section of the site. Some particularly have been found to play extremely important roles in the speed of aging and therefore the eventual lifespan of the organism.
Lifespan and general vigour have been increased in a number of species. From the nematode Caenorhabditis Elegans, the fruit fly Drosophila Melanogaster and the mouse Mus musculus, by the modulation of certain of these genes. In some cases longevity has been increased by a substantial degree!
Confirmed Longevity Genes
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Podospora |
Saccharomyces |
Caenorhabditis |
Drosophila |
Mouse |
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grisea |
LAG1 |
daf-2 |
sod1 |
Prop-1 |
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LAC1 |
age-1/daf-23 |
cat1 |
p66shc |
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RAS1 |
daf-18 |
mth |
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RAS2 |
akt-1/akt-2 |
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PHB1 |
daf-16 |
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PHB2 |
daf-12 |
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CDC7 |
ctl-1 |
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BUD1 |
old-1 |
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RTG2 |
spe-26 |
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RPD3 |
clk-1 |
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HDA1 |
mev-1 |
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SIR2 |
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SIR4-42 |
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UTH4 |
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YGL023 |
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SGS1 |
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RAD52 |
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FOB1 |
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The major genetic model organisms used in aging research are the filamentous fungus ('Podospora anserina'), bakers' yeast ('Saccharomyces cerevisiae'), the soil roundworm ('Caenorhabditis elegans'), the fruit fly ('Drosophila melanogaster'), and the mouse ('Mus musculus'). http://en.wikipedia.org/wiki/Longevity_genes
DNA Damage and Repair
DNA is the mechanism by which all of our physical characteristics and an increasingly large number of proven mental and social characteristics are passed on from one generation to the next. This applies to all living organisms, with the exception of a few basic forms, which use RNA to pass on their genetic information and thus characteristics, from one generation to the next.
As the genetic information is passed on between parent and offspring and during the course of an individual organisms lifetime, damage can and does occur to the DNA and thus to the genes. This damage as it occurs can result (depending also on a number of prevailing environmental factors) in the evolution of a species. This is broadly done in general accordance with the principles of Charles Darwin’s Natural Selection. When this damage occurs in a cumulative way through the course of an individual organisms lifetime however, the process eventually results in aging of the cells, tissues and organs, resulting eventually in cellular senescence and death.
A number of mechanisms have evolved in order to repair the damage to an organisms DNA. The purpose of this section of the site is to outline the different types of damage that can occur to DNA and what mechanisms are in place to limit the affects of this damage and to repair damage once it inevitably does occur.
So before outlining the state of the art knowledge on this very broad subject, here first are a few definitions.
Definition of DNA
Deoxyribonucleic acid; a nucleic acid that consists of two long chains of nucleotides twisted together into a double helix and joined by hydrogen bonds between complementary bases adenine and thymine or cytosine and guanine; it carries the cell's genetic information and hereditary characteristics via its nucleotides and their sequence and is capable of self-replication and RNA synthesis. http://www.answers.com/topic/dna
Note that where animal research is concerned, a distinction needs to be made between the DNA contained in the Nucleus of the cell, coiled up around beadlike histone proteins and coiled further into chromosomes and the DNA of the Mitochondria. To aid in this distinction, please find below a definition of Mitochondrial DNA (mtDNA).
Definition of Mitochondrial DNA
Mitochondrial DNA (mtDNA) is DNA that is located in mitochondria. This is in contrast to most DNA of eukaryotic organisms, which is found in the nucleus. It is often stated that 100% of the mtDNA contribution to a zygote is inherited from the mother, although this is controversial and may not be true for all organisms.
Unlike most of the cell, the function of which is defined by nuclear DNA, mitochondria have their own DNA and are assumed to have evolved separately. Human mitochondrial DNA consists of 5-10 rings of DNA and appears to carry 16,568 base pairs with 37 genes (13 proteins, 22 tRNAs and two rRNAs) which are concerned with the production of proteins involved in cellular respiration. However many proteins found in the mitochondria are encoded by nuclear DNA: some, if not most, are thought to have been originally part of the mitochondrial DNA but have since been transferred to the nucleus during evolution.
There is little change in the mtDNA from parent to offspring, unlike nuclear DNA which changes by 50% each generation. Since the mutation rate is easily measured, mtDNA is a powerful tool for tracking matrilineage, and has been used in this role for tracking many species back hundreds of generations. http://en.wikipedia.org/wiki/Mitochondrial_DNA
A Summary of DNA Damage and Repair
DNA repair is an integrated process whereby damage to the DNA of the cells genome is identified and then corrected. This DNA damage can occur as a result of a large number of normal metabolic activities. For example free radicals such as Hydrogen Peroxide H2O2 produced during cellular respiration can damage DNA quite severely. Also a variety of environmental factors, such as UV radiation and carcinogenic chemicals can and do result in damage to DNA.
This damage can result in lesions that may prevent the cell from being able to transcribe its genes, resulting in a loss of functionality of the cell. Other lesions can cause damage which does not affect the functionality of the cell itself, but does have an affect on any daughter cells that are produced following Mitosis. Perhaps resulting in the daughter cells functioning abnormally or being unable to survive.
Fortunately there are a number of DNA repair processes which strive to limit the affects of this damage. DNA repair is not perfect however. This means that over time the repair process will fail and a cell will enter one of the following states.
1. Apoptosis or cellular suicide. This is a process by which the cell destroys itself
2. Senescence. A process whereby the cell becomes irreversibly dormant
3. Uncontrolled cellular division. This can result in tumor formation and cancer
The effectiveness of the DNA repair mechanisms in a species have a direct relation to the average and maximum life expectancy of that species.