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The role of mitochondrial DNA mutations and free radicals in disease and ageing.

Lagouge M, Larsson NG - J. Intern. Med. (2013)

Bottom Line: Furthermore, interventions to modulate ROS levels in humans and animal models have not produced consistent results in terms of delaying disease progression and extending lifespan.A number of recent experimental findings strongly question the mitochondrial free radical theory of ageing, leading to the emergence of new theories of how age-associated mitochondrial dysfunction may lead to ageing.This novel view of ROS roles has a clear impact on the interpretation of studies in which antioxidants have been used to treat human age-related diseases commonly linked to oxidative stress.

View Article: PubMed Central - PubMed

Affiliation: Department of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, Cologne, Germany.

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Schematic representation of the mitochondrial free radical theory of ageing. Reactive oxygen species (ROS) are normal by-products of mitochondrial function that progressively damage the constituents of mitochondria, inducing mitochondrial dysfunction and increased ROS production through a vicious cycle, leading ultimately to cellular dysfunction and ageing.
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fig01: Schematic representation of the mitochondrial free radical theory of ageing. Reactive oxygen species (ROS) are normal by-products of mitochondrial function that progressively damage the constituents of mitochondria, inducing mitochondrial dysfunction and increased ROS production through a vicious cycle, leading ultimately to cellular dysfunction and ageing.

Mentions: The mitochondrial free radical theory (Fig. 1) postulates that ageing is caused by the toxicity of ROS, initiating a vicious cycle whereby damage to mtDNA and other mitochondrial constituents leads to RC dysfunction, which in turn leads to increased generation of ROS further facilitating mtDNA damage and thus creating a self-amplifying deterioration. This appealing theory provides a very interesting conceptual framework and has stimulated many crucial discoveries in the fields of mitochondrial function and ageing. However, this model has also been extensively debated as the links between the postulated underlying cornerstone mechanisms are rather correlative and as there is a lack of conclusive experimental evidence to support this theory. It is important to note that there have also been interesting attempts to unify this theory with other schemes, whereby age-related changes in the nucleus (e.g. telomere dysfunction) trigger mitochondrial dysfunction 5.


The role of mitochondrial DNA mutations and free radicals in disease and ageing.

Lagouge M, Larsson NG - J. Intern. Med. (2013)

Schematic representation of the mitochondrial free radical theory of ageing. Reactive oxygen species (ROS) are normal by-products of mitochondrial function that progressively damage the constituents of mitochondria, inducing mitochondrial dysfunction and increased ROS production through a vicious cycle, leading ultimately to cellular dysfunction and ageing.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3675642&req=5

fig01: Schematic representation of the mitochondrial free radical theory of ageing. Reactive oxygen species (ROS) are normal by-products of mitochondrial function that progressively damage the constituents of mitochondria, inducing mitochondrial dysfunction and increased ROS production through a vicious cycle, leading ultimately to cellular dysfunction and ageing.
Mentions: The mitochondrial free radical theory (Fig. 1) postulates that ageing is caused by the toxicity of ROS, initiating a vicious cycle whereby damage to mtDNA and other mitochondrial constituents leads to RC dysfunction, which in turn leads to increased generation of ROS further facilitating mtDNA damage and thus creating a self-amplifying deterioration. This appealing theory provides a very interesting conceptual framework and has stimulated many crucial discoveries in the fields of mitochondrial function and ageing. However, this model has also been extensively debated as the links between the postulated underlying cornerstone mechanisms are rather correlative and as there is a lack of conclusive experimental evidence to support this theory. It is important to note that there have also been interesting attempts to unify this theory with other schemes, whereby age-related changes in the nucleus (e.g. telomere dysfunction) trigger mitochondrial dysfunction 5.

Bottom Line: Furthermore, interventions to modulate ROS levels in humans and animal models have not produced consistent results in terms of delaying disease progression and extending lifespan.A number of recent experimental findings strongly question the mitochondrial free radical theory of ageing, leading to the emergence of new theories of how age-associated mitochondrial dysfunction may lead to ageing.This novel view of ROS roles has a clear impact on the interpretation of studies in which antioxidants have been used to treat human age-related diseases commonly linked to oxidative stress.

View Article: PubMed Central - PubMed

Affiliation: Department of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, Cologne, Germany.

Show MeSH
Related in: MedlinePlus