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The benefits of physical activity in preventing premature mortality have been established by a large set of epidemiological studies. These benefits have been shown both in middle-aged and elderly individuals. Furthermore, the reduction of acute events such as myocardial infarction observed with higher levels of physical activity together with the increase in disease-free life expectancy among the most active individuals supports physical activity's antiaging effect. This review highlights two models supporting this effect. The first model describes the path to frailty and the second explains that immobilization is a stressor which triggers stress-responses responsible for many chronic diseases. Aging reduces the physiological reserve and can lead to frailty when this reserve cannot allow an appropriate adaptation of the aging body to environmental challenges. The components of this physiological reserve can easily be measured by cardiorespiratory testing. Among them are heart rate reserve and VO(2)max, the maximal body oxygen consumption. The opposite effects of exercise training and aging on the physiological reserve are detailed. Sedentary lifestyle accelerates the effects of aging in susceptible individuals. Sedentary lifestyle induces mechanisms which lead to risk factors of chronic diseases and, eventually, to premature death. These inappropriate mechanisms and their consequences constitute the sedentary lifestyle syndrome., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)