Translational studies of chronic supplementation with a mitochondria-targeted antioxidant to improve physical function with ageing.

Abstract

Declines in physical function with advancing age increase the risk of functional limitations and chronic disease. Excess mitochondrial reactive oxygen species (mitoROS)-related oxidative stress is linked to physical dysfunction with ageing, but the effects of therapies targeting excess mitoROS on age-associated physical dysfunction are unclear. Here, we determined the efficacy of the mitochondria-targeted antioxidant MitoQ for improving multiple domains of physical function, first in old mice and then in high-functioning older adults in a randomized, placebo-controlled, cross-over design clinical trial. In old male C57BL6/N mice (N = 22-26; 27 months), we found that 4 weeks of treatment with MitoQ (250 µm in the drinking water) attenuated the age-related decline in grip strength, co-ordination, and endurance without effects in young mice (N = 18-20; 6 months). The effects of MitoQ in old mice were accompanied by lower levels of skeletal muscle mitochondria-specific superoxide production and markers of mitoROS-related oxidative stress (i.e. phosphorylated SHC adaptor protein 1, isoform p66) and inflammation (i.e. interleukin-6, tumour necrosis factor-alpha, interferon-gamma). In the clinical trial, we did not observe convincing effects of 6 weeks of MitoQ (20 mg day