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Recent Abstracts

Defending against age and disease

Kevin E. Conley
University of Washington

Reactive oxygen species (ROS) are implicated in oxidative damage but at low levels act as signals, especially in exercise.  Here we show that mitochondria co-opt these signaling pathways to coordinate the defense against ROS or to reverse the failed defenses that occur with age and disease.  These insights are possible with innovative spectroscopic tools applied to two human conditions with oxidative stress but prior to development of oxidative damage (pre-symptomatic Huntington’s disease and cancer survivors), as well as to human aging.  The presymptomatic subjects reveal the integrated response to disease stress coordinated by mitochondria:  an increase in mitochondrial uncoupling (reduced ATP per O2), mobilization of metabolism and activation of mitochondrial biogenesis.  A failure of this coordinated response is apparent with age and symptomatic disease as shown by reduced metabolism, impaired biogenesis and loss of cellular ATP.  Rejuvenation of the integrated response is found in elderly muscle with exercise training.  Elevation of mitochondrial biogenesis and improved mitochondrial uncoupling occurs with daily exercise in old subjects.  These results suggest that mitochondria coordinate the first line of defense in response to elevated ROS.  The resulting series of compensatory cellular changes ameliorate the impact of oxidative stress and activate cellular metabolism in a manner similar to the effect of exercise.  Use of exercise as a treatment helps reactivate these defenses to reverse some key age-related changes.  These results suggest why chronic activity has both health and anti-aging benefits.  Exercise-stimulated pathways provide a defense against the oxidative stress common to many diseases and as well as cellular aging.  Supported by AG028455, AR041928, AR036606, CA103728 and the CHDI Foundation.