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A somatic mutation is a change in the DNA sequence of a somatic cell of a multicellular organism with dedicated reproductive cells; that is, any mutation that occurs in a cell other than a gamete, germ cell, or gametocyte.
DNA damage in non-replicating cells, if not repaired and accumulated can lead to aging. DNA damage in replicating cells, if not repaired can lead to either apoptosis or to cancer. The schematic diagram indicates the roles of insufficient DNA repair in aging and cancer, and the role of apoptosis in cancer prevention.
A related theory is that mutation, as distinct from DNA damage, 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. [49]
As well as mutations to DNA damage repair genes, mutations also arise in the genes responsible for arresting the cell cycle to allow sufficient time for DNA repair to occur, and some genes are involved in both DNA damage repair and cell cycle checkpoint control, for example ATM and checkpoint kinase 2 (CHEK2) – a tumor suppressor that is ...
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]
Mutation and DNA damage are the two major types of errors that occur in DNA, but they are fundamentally different. DNA damage is a physical alteration in the DNA structure, such as a single or double strand break, a modified guanosine residue in DNA such as 8-hydroxydeoxyguanosine, or a polycyclic aromatic hydrocarbon adduct. DNA damages can be ...
The likely major underlying cause of mutations in cancer is DNA damage. [citation needed] For example, in the case of lung cancer, DNA damage is caused by agents in exogenous genotoxic tobacco smoke (e.g. acrolein, formaldehyde, acrylonitrile, 1,3-butadiene, acetaldehyde, ethylene oxide and isoprene). [25]
Therefore, a greater investment in growth and reproduction would result in reduced investment in DNA repair maintenance, leading to increased cellular damage, shortened telomeres, accumulation of mutations, compromised stem cells, and ultimately, senescence. Although many models, both animal and human, have appeared to support this theory ...