The historical context and scientific legacy of John O. Holloszy.

John O. Holloszy, as perhaps the world's preeminent exercise biochemist/physiologist, published >400 papers over his 50+ year career, and they have been cited >41,000 times. In 1965 Holloszy showed for the first time that exercise training in rodents resulted in a doubling of skeletal muscle mitochondria, ushering in a very active era of skeletal muscle plasticity research. He subsequently went on to describe the consequences of and the mechanisms underlying these adaptations. Holloszy was first to show that muscle contractions increase muscle glucose transport independent of insulin, and he studied the mechanisms underlying this response throughout his career. He published important papers assessing the impact of training on glucose and insulin metabolism in healthy and diseased humans. Holloszy was at the forefront of rodent studies of caloric restriction and longevity in the 1980s, following these studies with important cross-sectional and longitudinal caloric restriction studies in humans. Holloszy was influential in the discipline of cardiovascular physiology, showing that older healthy and diseased populations could still elicit beneficial cardiovascular adaptations with exercise training. Holloszy and his group made important contributions to exercise physiology on the effects of training on numerous metabolic, hormonal, and cardiovascular adaptations. Holloszy's outstanding productivity was made possible by his mentoring of ~100 postdoctoral fellows and substantial NIH grant funding over his entire career. Many of these fellows have also played critical roles in the exercise physiology/biochemistry discipline. Thus it is clear that exercise biochemistry and physiology will be influenced by John Holloszy for numerous years to come.