How increased oxidative stress promotes longevity and metabolic health: The concept of mitochondrial hormesis (mitohormesis)

Dept. of Human Nutrition, Institute of Nutrition, University of Jena, Germany. <>
Experimental gerontology (Impact Factor: 3.49). 03/2010; 45(6):410-8. DOI: 10.1016/j.exger.2010.03.014
Source: PubMed


Recent evidence suggests that calorie restriction and specifically reduced glucose metabolism induces mitochondrial metabolism to extend life span in various model organisms, including Saccharomyces cerevisiae, Drosophila melanogaster, Caenorhabditis elegans and possibly mice. In conflict with Harman's free radical theory of aging (FRTA), these effects may be due to increased formation of reactive oxygen species (ROS) within the mitochondria causing an adaptive response that culminates in subsequently increased stress resistance assumed to ultimately cause a long-term reduction of oxidative stress. This type of retrograde response has been named mitochondrial hormesis or mitohormesis, and may in addition be applicable to the health-promoting effects of physical exercise in humans and, hypothetically, impaired insulin/IGF-1-signaling in model organisms. Consistently, abrogation of this mitochondrial ROS signal by antioxidants impairs the lifespan-extending and health-promoting capabilities of glucose restriction and physical exercise, respectively. In summary, the findings discussed in this review indicate that ROS are essential signaling molecules which are required to promote health and longevity. Hence, the concept of mitohormesis provides a common mechanistic denominator for the physiological effects of physical exercise, reduced calorie uptake, glucose restriction, and possibly beyond.

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    • "The term mitohormesis describes health effects of exercise through affecting mitochondrial performance by inducing mild oxidative stress and cellular adaptation [22]. Indeed, mitohormesis protects the cells against more severe and potent cellular stressors. "
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    • "CR was originally thought to slow aging by reducing mitochondrial ROS generation. However, recent studies have revealed that mitochondrial respiration and ROS are not necessarily decreased but are actually increased by CR (Ristow et al. 2010). In Fig. 7 Cox6b1 overexpression induces Nrf2 nuclear translocation and upregulates antioxidant enzymes. "
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    • "Thus increased ROS production has now come to be viewed as an adaptive response of mitochondria [16], often called mitohormesis, to mitigate dangerous changes rather than representing an inevitable byproduct of mitochondrial respiration. Mitohormesis also increases stress resistance, maintains mtDNA levels, preserves mtDNA fidelity, enables cells to tolerate high levels of mtDNA mutations [33], and generally prolongs lifespan [34] [35] [36]. This represents a novel-upsetting paradigm, which explains the failure of antioxidants to delay aging in clinical trials [37] [38]. "
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