Role of Inactivity in Chronic Diseases: Evolutionary Insight and Pathophysiological Mechanisms

Physiol Rev. 2017 Oct 1;97(4):1351-1402. doi: 10.1152/physrev.00019.2016.


This review proposes that physical inactivity could be considered a behavior selected by evolution for resting, and also selected to be reinforcing in life-threatening situations in which exercise would be dangerous. Underlying the notion are human twin studies and animal selective breeding studies, both of which provide indirect evidence for the existence of genes for physical inactivity. Approximately 86% of the 325 million in the United States (U.S.) population achieve less than the U.S. Government and World Health Organization guidelines for daily physical activity for health. Although underappreciated, physical inactivity is an actual contributing cause to at least 35 unhealthy conditions, including the majority of the 10 leading causes of death in the U.S. First, we introduce nine physical inactivity-related themes. Next, characteristics and models of physical inactivity are presented. Following next are individual examples of phenotypes, organ systems, and diseases that are impacted by physical inactivity, including behavior, central nervous system, cardiorespiratory fitness, metabolism, adipose tissue, skeletal muscle, bone, immunity, digestion, and cancer. Importantly, physical inactivity, itself, often plays an independent role as a direct cause of speeding the losses of cardiovascular and strength fitness, shortening of healthspan, and lowering of the age for the onset of the first chronic disease, which in turn decreases quality of life, increases health care costs, and accelerates mortality risk.

Publication types

  • Review

MeSH terms

  • Adipose Tissue / physiology
  • Animals
  • Biological Evolution*
  • Bone and Bones / physiology
  • Cardiorespiratory Fitness
  • Central Nervous System / physiology
  • Chronic Disease*
  • Digestion
  • Humans
  • Immunity
  • Metabolism
  • Muscle, Skeletal / physiology
  • Neoplasms / etiology
  • Sedentary Behavior*