The free-radical theory of ageing--older, wiser and still alive: modelling positional effects of the primary targets of ROS reveals new support.
The continuing viability of the free-radical theory of ageing has been questioned following apparently incompatible recent results. We show by modelling positional effects of the generation and primary targets of reactive oxygen species that many of the apparently negative results are likely to be misleading. We conclude that there is instead a need to look more closely at the mechanisms by which free radicals contribute to age-related dysfunction in living systems. There also needs to be deeper understanding of the dynamics of accumulation and removal of the various kinds of molecular damage, in particular mtDNA mutations. Finally, the expectation that free-radical damage on its own might cause ageing needs to be relinquished in favour of the recognition that the free-radical theory is just one of the multiple mechanisms driving the ageing process.
Centre for Integrated Systems Biology of Ageing and Nutrition, Institute for Ageing and Health, Newcastle University, Newcastle Upon Tyne, UK. tom.kirkwood@ncl.ac.uk
Thomas B L
TB
Kirkwood
Axel
A
Kowald
D000375:Aging / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000235:genetics / Q000502:physiology; D051336:Mitochondrial Membranes / Q000378:metabolism; D008958:Models, Molecular; D019577:Mole Rats / Q000378:metabolism / Q000502:physiology; D009154:Mutation; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012641:Selection, Genetic
D000975:Antioxidants; D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species