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| Content Provider | frontiers |
|---|---|
| Author | Ziada, Adam S. Smith, Marie-Soleil R. Côté, Hélène C. F. |
| Abstract | The free radical theory of aging implicates the gradual accumulation of oxidative cellular damage as a fundamental driver of cellular aging (Harman., 1956, Miquel et al., 1980. This theory has evolved over time to emphasize the role of free radical induced mitochondrial DNA (mtDNA) mutations and the accumulation of mtDNA deletions (Miquel et al., 1980, Michikawa et al., 1999, Cortopassi et al., 1992.Given the proximity of mtDNA to the electron transport chain, a primary producer of free radicals, it postulates that the mutations would promote mitochondrial dysfunction and concomitantly increase free radical production in a positive feedback loop. The observation of oxidative damage in the form of 7,8-dihydro-8-oxo-deoxyguanosine (8-oxodG) DNA oxidative lesions accumulating with age has been a cornerstone of the free radical theory of aging (Fraga et al., 1990).A major assumption of the free radical theory of aging is that random de novo or somatic mtDNA mutations gradually accumulate over time, eventually reaching pathological levels. However, data from Payne et al support the hypothesis that, rather than gradually accumulating over time, mtDNA turnover can lead to the clonal expansion of pre-existing age-related mutations (Payne et al., 2011). Once amplified, these higher frequency mtDNA mutations, that are potentially pathogenic, are referred to as heteroplasmy.To further understand the potential link between mtDNA mutations and the free radical theory of aging, our grou... |
| ISSN | 2296634X |
| DOI | 10.3389/fcell.2020.575645 |
| Volume Number | 8 |
| Journal | Frontiers in Cell and Developmental Biology |
| Language | English |
| Publisher Date | 2020-09-16 |
| Access Restriction | Open |
| Subject Keyword | MtDNA Polymerase gamma (POLG) Aging MtDNA mutations Mitochondrial biogenesis MtDNA replication Free radical theory of aging Clonal expansion Oxidative Stress |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Developmental Biology |
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