Extending life span by increasing oxidative stress.

By Michael Ristow, S. Schmeisser. Free Radical Biology & Medicine, 2011

696 citations recorded by the source corpus.

Various nutritional, behavioral, and pharmacological interventions have been previously shown to extend life span in diverse model organisms, including Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, mice, and rats, as well as possibly monkeys and humans. This review aims to summarize published evidence that several longevity-promoting interventions may converge by causing an activation of mitochondrial oxygen consumption to promote increased formation of reactive oxygen species (ROS). These serve as molecular signals to exert downstream effects to ultimately induce endogenous defense mechanisms culminating in increased stress resistance and longevity, an adaptive response more specifically named mitochondrial hormesis or mitohormesis. Consistently, we here summarize findings that antioxidant supplements that prevent these ROS signals interfere with the health-promoting and life-span-extending capabilities of calorie restriction and physical exercise. Taken together and consistent with ample published evidence, the findings summarized here question Harman's Free Radical Theory of Aging and rather suggest that ROS act as essential signaling molecules to promote metabolic health and longevity.

Subfields: Aging, Physiology

View Paper: https://www.semanticscholar.org/paper/281bfe2c2b5fc542093e6aed2d7c2365c862896b

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Citations in the corpus

ROS Function in Redox Signaling and Oxidative Stress (2014, background): “On the contrary, recent evidence suggests that ROS signaling is required for the maintenance of tissues and that increasing ROS can activate cellular stress pathways to dampen tissue degeneration and promote healthy aging [108].”
ROS, Cell Senescence, and Novel Molecular Mechanisms in Aging and Age-Related Diseases (2016, background): “Mitochondrial ROS may activate an adaptive response (mitohormesis), which, as defensive mechanism, promotes health to extend the lifespan through diseases prevention and delay [5, 85].”
Role of ROS and RNS Sources in Physiological and Pathological Conditions (2016, background): “It has also been shown that whereas accumulation of oxidative damage results in organism death [15], several longevity-promoting interventions increase generation of ROS that activate stress responses that are beneficial to the organism and extend lifespan [16].”
Mitochondrial ROS signaling in organismal homeostasis. (2015, background): “While the above discussion was limited largely to examples from worms and yeast, it is important to note that similar mtROS longevity pathways have been shown to operate in other invertebrates and in mice (Hekimi et al., 2011; Ristow and Schmeisser, 2011).”
Oxidative Stress in Cardiovascular Diseases: Still a Therapeutic Target? (2019, background): “It has been suggested that the indiscriminate use of antioxidants may even be harmful [156].”
The hallmarks of aging. (2013, background): “These and other data have paved the way to a reconsideration of the role of ROS in aging (Ristow and Schmeisser, 2011).”
Proposed Mechanisms of Photobiomodulation or Low-Level Light Therapy (2016, background): “ROS are produced at a low level by normal mitochondrial metabolism [61].”
The emerging role of reactive oxygen and nitrogen species in redox biology and some implications for plasma applications to medicine and biology (2012, background): “With respect to the effects of ROS on organism lifetime, there is some evidence now that ROS, acting through mitochondrial metabolism, are sometimes associated with increased lifespan, as described by Ristow and Zarse [15], Ristoe and Schmeisser [16] and Hekimi et al [17].”