Mitochondrial ROS-induced ROS release:changes with aging

Aging

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Abstract

A fundamental element of the "theory of aging" implicates a critical role of free radicals, principally due to ROS of mitochondrial origin. Individual mitochondria, in isolated cardiac myocytes, loaded with membrane potential (delta PSI)- and ROS-sensitive fluorophores and excited with scanning laser light show an abrupt loss of delta PSI coinciding with a burst of mitochondrial ROS-production, which we termed "ROS-induced ROS release". This loss of delta PSI is due to ROS-induction of the mitochondrial permeability transition (MPT). Hypothesizing that aging is accompanied by an increasing sensitivity to free radical stress, we compared the susceptibility to MPT-induction by ROS (characterized as the time necessary for ROS produced via photoexcitation to induce the MPT) in myocytes from young (2-4 month) and old (24 month) rats. Compared to young rats, MPT-induction times in the aged rats were reduced by 40%, whilst the magnitude of the ROS-burst was significantly increased. This enhanced sensitivity to ROS in the aged group was largely abolished by Coenzyme Q10 supplementation, an effect unlikely to be due to non-specific ROS-scavenging because the ROS-sensitivity of young cells was unaffected by this treatment. Thus, the age-related enhancement in ROS-sensitivity in cardiac myocytes from aged rats may be the result of specific loss of respiratory chain constituents.