IMR Press / FBL / Volume 13 / Issue 17 / DOI: 10.2741/3174

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Article

The mitochondrial free radical theory of ageing – where do we stand?

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1 National University of Singapore, Department of Biochemistry, Centre for Life Sciences, 28 Medical Drive, 117456 Singapore

*Author to whom correspondence should be addressed.

 

Front. Biosci. (Landmark Ed) 2008, 13(17), 6554–6579; https://doi.org/10.2741/3174
Published: 1 May 2008
Abstract

Understanding the molecular mechanisms underlying the ageing process may provide the best strategy for addressing the challenges posed by ageing populations worldwide. One theory proposing such molecular mechanisms was formulated 50 years ago. Harman et al. suggested that ageing might be mediated by macromolecular damage through reactions involving reactive oxygen species (ROS). Today, a version of the free radical theory of ageing, focusing on mitochondria as source as well as target of ROS, is one of the most popular theories of ageing. Here we critically review the status of key principles and concepts on which this theory is based. We find that the evidence to date shows that many of the original assumptions are questionable, while on some critical issues further refinements in techniques are required. Even so, it is becoming evident that mitochondria and mtDNA integrity may indeed be crucial determinants of organismal ageing. Implications for the prospect of successful interventions as well as evidence for and against efficacy of current therapeutic approaches are discussed.

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