Fight Aging!

Targeting antioxidants to the mitochondria inside cells has been shown to produce enough of a benefit to build therapies for a number of conditions, with better outcomes than standard antioxidant treatments. Researchers developing mitochondrially targeted antioxidants based on plastinquinones are still searching for potential clinical applications, however, and in the recent paper referenced here they demonstrate benefits in skin healing for aged mice.

Mitochondria produce reactive oxidizing molecules as a side-effect of their operation. Soaking up some of these molecules at the source has more and better effects on cellular metabolism than the introduction of non-targeted antioxidants, including in some cases extension of healthy life. The reasons for this are complex and still incompletely understood: the emitted reactive molecules are an important signal in addition to being agents that cause damage, cells react to both signals and damage, and among the interventions that slow aging in lower animals some involve greater and some involve lesser generation of reactive molecules in mitochondria. Regarding non-targeted antioxidants, the general consensus at this time is that antioxidant supplementation as a matter of course is probably mildly harmful, as it interferes with hormetic processes based on use of reactive molecules as signals such as those that mediate the beneficial effects of exercise.

The process of skin wound healing is delayed or impaired in aging animals. To investigate the possible role of mitochondrial reactive oxygen species (mtROS) in cutaneous wound healing of aged mice, we have applied the mitochondria-targeted antioxidant SkQ1. The SkQ1 treatment resulted in accelerated resolution of the inflammatory phase, formation of granulation tissue, vascularization and epithelization of the wounds. The wounds of SkQ1-treated mice contained increased amount of myofibroblasts which produce extracellular matrix proteins and growth factors mediating granulation tissue formation. This effect resembled SkQ1-induced differentiation of fibroblasts to myofibroblast, observed earlier in vitro.

The transforming growth factor beta (TGFb) produced by SkQ1-treated fibroblasts was found to stimulated motility of endothelial cells in vitro, an effect which may underlie pro-angiogenic action of SkQ1 in the wounds. In vitro experiments showed that SkQ1 prevented decomposition of VE-cadherin containing contacts and following increase in permeability of endothelial cells monolayer, induced by pro-inflammatory cytokine TNF. Prevention of excessive reaction of endothelium to the pro-inflammatory cytokine(s) might account for anti-inflammatory effect of SkQ1. Our findings point to an important role of mtROS in pathogenesis of age-related chronic wounds.

Link: http://www.impactaging.com/papers/v7/n7/full/100772.html