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The mutation accumulation theory of aging was first proposed by Peter Medawar in 1952 as an evolutionary explanation for biological aging and the associated decline in fitness that accompanies it. [1] Medawar used the term 'senescence' to refer to this process.
The somatic mutation theory of ageing states that accumulation of mutations in somatic cells is the primary cause of aging. A comparison of somatic mutation rate across several mammal species found that the total number of accumulated mutations at the end of lifespan was roughly equal across a broad range of lifespans. [16]
The free-radical theory of aging proposes that this damage cumulatively degrades the biological function of cells and impacts the process of aging. [18] The idea that free radicals are toxic agents was first proposed by Rebeca Gerschman and colleagues in 1945, [19] but came to prominence in 1956, when Denham Harman proposed the free-radical ...
The DNA damage theory of aging proposes that aging is a consequence of unrepaired accumulation of naturally occurring DNA damage. Damage in this context is a DNA alteration that has an abnormal structure. Although both mitochondrial and nuclear DNA damage can contribute to aging, nuclear DNA is the main subject of this analysis.
The metabolic stability theory of aging suggests it is the cells ability to maintain stable concentration of ROS which is the primary determinant of lifespan. [37] This theory criticizes the free radical theory because it ignores that ROS are specific signalling molecules which are necessary for maintaining normal cell functions. [37]
A mutation accumulation (MA) experiment is a genetic experiment in which isolated and inbred lines of organisms (so-called MA lines) are maintained such that the effect of natural selection is minimized, with the aim of quantitatively estimating the rates at which spontaneous mutations (mutations not caused by exogenous mutagens) occur in the studied organism.
The term is most widely used to refer to mutation accumulation to the point of inviability of the organism or virus, where it cannot produce enough viable offspring to maintain a population. This use of Eigen's term was adopted by Lawrence Loeb and colleagues to describe the strategy of lethal mutagenesis to cure HIV by using mutagenic ...
Cross-links. Crosslinking of DNA; Free radicals – atom, molecule, or ion that has unpaired valence electrons. With some exceptions, these unpaired electrons make free radicals highly chemically reactive towards other substances, or even towards themselves: their molecules will often spontaneously dimerize or polymerize if they come in contact with each other.