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

Abstract

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.

Copyright © 2017 the American Physiological Society.

Figures

FIGURE 1.

Spectrum of the types of physical inactivity. Following the arrow from right (low intensity of physical inactivity) to left (high intensity of physical inactivity) shows our estimate of the intensity of physical inactivity per unit of time. Not shown is the volume (intensity × duration) of physical inactivity. For example, spinal cord severance is high intensity and health decrements appear within days. In opposite manner, sitting is low intensity, with long-term health effects not clinically apparent within days, but nonetheless unhealthy when first appearing after many years.

FIGURE 2.

Parents provide their offspring with genes and environment, which both produce physical inactivity. Physical inactivity interacts with inherited gene predisposition of offspring to produce pathophysiology, which, in turn, interacts with risk factors to establish probability for chronic disease and mortality.

FIGURE 3.

Physical inactivity increases 35 chronic diseases. See Booth et al. (55) for more details on how physical inactivity is a major cause of chronic diseases.

FIGURE 4.

Chronic physical inactivity initiates a cascade of events. Physical inactivity is an actual cause of the numerous abnormal physiological values (physiological dysfunctions) that, in turn, cause usually permanent pathological changes (pathophysiology), which over time lead to overt diagnosed chronic diseases, that culminate as contributors to premature mortality. Two categories of physical activity are presented: voluntary physical activity, which commonly serves in primary prevention of pathophysiology, and prescribed physical activity, which is shown for common usage of secondary prevention of existing chronic disease.

FIGURE 5.

Overview of physical inactivity’s interactions. The three terms inside the triangle (chronic disease, genes, and environment) all interact directly with physical inactivity, and physical inactivity can directly influence them. The green circle indicates that evolution has and continues to play a role in shaping the interactions of all the terms inside the triangle.

FIGURE 6.

Increasing obesity and decreasing voluntary physical activity as a function of age in youth. A: percentage of overweight or obese (BMI for age grouping ≥85th percentile of the Centers for Disease Control Growth Charts) in the three age ranges increases from 2 to 5 yr (infants) to 6–11 yr (children) and 12–19 yr (adolescents) as originally presented in JAMA by Ogden et al. (369). B: best-fit lines for ages ascending from 6 to 19 yr old are descending curves that represent the 50th percentile of females and males. Accelerometer-determined moderate-to-vigorous physical activity decreases during 6–11 yr old ages and then plateaued during 12–18 yr old age range. [Modified from Wolff-Hughes et al. (547).] C: second confirming study to B that accelerometer-based moderate-to-vigorous physical activity decreased during 6–11 yr old age range and then began to asymptope during 12–18 yr old age range. [Redrawn from Trost et al. (506), with permission from Medicine and Science in Sports and Exercise.]

FIGURE 7.

The age span shown for equivalent maximal oxygen consumption (V̇o2max) values is many decades later in life in a comparison of lifelong masters athletes (A), endurance-trained (B), or octogenarian endurance athletes (C) to V̇o2max values in younger, sedentary subjects. Data set 1: ~80-yr-old masters athletes’ V̇o2max was equivalent to lean untrained men, aged ~30 yr old, which is a >5 decades difference between trained and untrained humans (A). Similar decades’ difference for V̇o2max between lifelong trained and sedentary groups were published in two later publications. Data set 2: a >3 decades earlier in life equivalent V̇o2max was reported in younger sedentary as compared with the endurance-trained athletes (B). Data set 3: a >2–3 decades earlier in life for V̇o2max value was found in normative octogenarians who were lifelong, octogenarian athletes (C). Data in the panels were obtained by copying curvilinear lines from the original figure. Each line begins as early as the age of 20 yr old and ends at the oldest age group reported in each original figure. Superimposed upon each curvilinear line are dashed lines with arrows so to form a 3-sided-rectangle above each solid curved line. The vertical dashed line furthest to the right has an upward pointed arrow extending from the oldest age at which V̇o2max was determined, intercepting at the endurance-training V̇o2max curvilinear line. The second dashed line is horizontal and extends left to intercept the lower curvilinear line for the lesser V̇o2max. The final line in series of three dashed lines is a vertical drop-down from its interception point upon descending V̇o2max line. [A from Heath et al. (208). B from Tanaka and Seals (484). C from Trappe et al. (501).]

FIGURE 8.

Relative risk of death for all MET values (x-axis) for 10 and greater are all similar during maximal aerobic-type exercise. When METs fall from ~10 to 4 with aging, risk of death increases 4-fold. Three studies are shown, with each from a different decade. Study 1: Blair et al.’s 1989 study (44) of relative risk of death (left y-axis) includes both male and female data from original Figure 4 in JAMA (shown within ovals). Study 2: Kokkinos’ 2008 study in Circulation (256) is relative risk of death in males (shown in rectangles). Study 3: Al-Mallah et al.’s 2016 publication in Mayo Clinic Proceedings (4) shows mortality rate (right y-axis) females (blue line and black circles) and males (red line and black diamonds) with the outer lines showing the 95% confidence intervals.

FIGURE 9.

Adjusted odds ratio of clustering of cardiorespiratory risk factors in combined categories of fitness and sedentary time in men with decreasing cardiovascular fitness levels. Low, moderate, and high CRF levels were defined as the least fit 20%, the next fit 40%, and the most fit 40%, respectively, corresponding to 43.3 ml·kg-1·min-1 in men. Sedentary time is reported as ≤4 h (black bars), 5–7 h (dark gray bars), and ≥7 h (light bars) *Significant difference (P < 0.05) from reference category. [Data from Nauman et al. (351), with permission from Medicine and Science in Sports and Exercise.]

FIGURE 10.

Schematic of metabolic dysfunctions produced by physical inactivity in white adipose tissue and skeletal muscle.

FIGURE 11.

Schematic of two factors, physical inactivity and aging, that produce sarcopenia and its associated eventual loss of an important functional reserve.