Extending life span by increasing oxidative stress

Abstract

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.

Lifespan effects of simple and complex nutraceutical combinations fed isocalorically to mice

“…None of the combinations extended lifespan, and one very complex mixture of supplements decreased lifespan. These results are consistent with other rodent studies indicating that nutraceutical supplements have no effect on lifespan, or shorten it (Ristow and Schmeisser 2011;Selman et al 2013;Spindler et al 2013b). Our results also are consistent with studies of initially healthy humans indicating that the use of dietary supplements is associated with either no effect or a negative effect on survival (e.g., Bjelakovic et al 2004; Chowdhury et al Macpherson et al 2013;Miller et al 2005;Myung et al 2013;Rizos et al 2012).…”

Cerium oxide nanoparticles protect against Aβ-induced mitochondrial fragmentation and neuronal cell death

“…This phenomenon--in which mild stressors such as caloric restriction and physical exercise induce increased mitochondrial activity, transient ROS formation, and downstream adaptive antioxidant responses--has been documented in multiple model systems. 55 Thus, an important issue to consider and an alternative explanation for the clinical ineffectiveness of antioxidant therapies to date is disruption of these adaptive response systems. Eradication of the cytoprotective effects of mild stress and undesirable downstream consequences could be particularly problematic for stable, long-acting antioxidants, such as nanoceria.…”

Protection or cytotoxicity mediated by a novel quinonoid-polyphenol compound?

“…xenohormesis), hormetic stressors might include also caloric restriction, cold temperature, heat shock or physical exercise. Furthermore, caloric restriction and moderate physical activity were proposed to control the ageing process through enhanced mitochondrial activity and subsequently increased reactive oxygen species (ROS) formation that finally induce an adaptive response culminating in metabolic health and extended longevity (Ristow and Schmeisser 2011). This adaptive response is more specifically named mitochondrial hormesis or mitohormesis, which is in conflict with the extended Harman's free radical theory of aging (FRTA) explaining ageing as a consequence of mitochondrial accumulation of ROS over time (Harman 1972).…”