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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]
Replication may also be blocked and/or the cell may die. Descriptions of reduced function, characteristic of aging and associated with accumulation of DNA damage, are described in the next section. [citation needed] In contrast to DNA damage, a mutation is a change in the base sequence of the DNA.
DNA damage is an abnormal chemical structure in DNA, while a mutation is a change in the sequence of standard base pairs. The theory that DNA damage is the primary cause of aging is based, in part, on evidence in human and mouse that inherited deficiencies in DNA repair genes often cause accelerated aging. [29] [30] [27] There is also ...
This reflects the accumulation of DNA damage with age. DNA damage accumulation with age is further described in DNA damage theory of aging. Swenberg et al. [30] measured average amounts of selected steady state endogenous DNA damages in mammalian cells. The seven most common damages they evaluated are shown in Table 1.
Many life span influencing genes affect the rate of DNA damage or DNA repair. Genetics of aging is generally concerned with life extension associated with genetic alterations, rather than with accelerated aging diseases leading to reduction in lifespan. The first mutation found to increase longevity in an animal was the age-1 gene in ...
All evolutionary theories of aging rest on the basic mechanisms that the force of natural selection declines with age. [19] [20] Mechanistic theories of aging can be divided into theories that propose aging is programmed, and damage accumulation theories, i.e. those that propose aging to be caused by specific molecular changes occurring over time.
During aging, the efficiency of mitochondria tends to decrease. The reasons for this are still quite unclear, but several mechanisms are suspected: reduced biogenesis, [32] accumulation of damage and mutations in mitochondrial DNA, oxidation of mitochondrial proteins, and defective quality control by mitophagy. [33]