Increasing the health span: unique role for exercise

Abstract

Health span, that period between birth and onset of major disease(s), when adequate physical and cognitive function permit those daily living activities essential to life quality, is lower in the United States than other developed countries. Physical inactivity and excessive calorie intake occupy dominant roles both in the problem, and by redressing them, in the solution. Consequently, this review focuses on evidence that appropriate exercise engagement and calorie restriction (CR) can improve physical and mental health with a view to extending the health span. Humanity, writ large, has grasped these underlying concepts for Millennia but has been largely intransigent to them. Thus, the final section proposes a novel Monty Python-esque approach that encompasses humanity's inimical sense of humor to increase physical fitness and mental health, restore energy balance, sustain better cognitive function, and extend the health span.

Keywords: V̇o2max; calorie restriction; cardiorespiratory fitness; cognitive function; physical activity.

Figure 1.

Schematic depicting the current U.S. health span which, at 66.1 years, lags behind that of most developed countries and sentences the majority of Americans to well over a decade of morbidity presaging the increased likelihood of dependent care when the maximal oxygen uptake ($\dot{\text{V}}{\text{O}}_2\text{max}$) falls below ~20 ml · kg⁻¹ · min⁻¹ (black curve). This review explores the evidence for, and potential of, exercise and calorie restriction to extend the health span (grey arrow, brown curve) such that the period of morbidity is reduced to just a few months or years immediately preceding death. Please note that this is a hypothetical schematic where age should not be necessarily regarded as a continuous variable. Moreover, it is to be expected that substantial variation exists across sexes, ethnic groups, genetic predisposition and disparate lifestyle factors (e.g., dietary patterns, exercise type and characteristics, family income, smoking, drug use) of the individual, most of which have yet to be defined in the context of health span and, as such, are beyond the scope of this review. See text for more details.

Figure 2.

All-cause mortality risk associated with increasing cardiorespiratory fitness (CRF), increasing physical activity (PA), and intentional weight loss. For CRF and PA, cohorts consisted of middle-aged and older adults with no reported major health conditions at baseline. For intentional weight loss, the meta-analyses of randomized controlled trials generally consisted of adults with overweight or obesity and with 1 or more chronic health conditions (e.g., hypertension, impaired glucose tolerance, T2D, CVD). For Harrington, “healthy” and “unhealthy” were defined as “with” or “without” obesity-related risk factors. Sample sizes for meta-analyses: Harrington (2009; 10 studies; n = 28,672); Chen (2018; 3 studies; n = 6,875); Pack (2014; 1 study; n = 377); Singh (2019; 33 studies; n = 19,379); Kritchevsky (2015; 12 studies; n = 15,306; Ma (2017; 34 studies; n = 22,779); Schellenberg (2013; 2 studies; n = 5,305). The horizontal lines represent the upper and lower 95% confidence intervals (CI) for the respective risk ratio for each study. The mortality risk ratios for increasing CRF and PA are generally much lower than those for intentional weight loss, with the upper boundary of the 95% CI more consistently < 1.0.

Figure 3.

Comparison of weight loss vs. increasing physical activity (PA) and cardiorespiratory fitness (CRF) for obesity treatment. Increasing PA, especially via exercise of sufficient stimulus to improve both CRF and muscular fitness, may or may not change body weight or total body fat, but health improvements are largely independent of weight loss. By contrast, a weight-loss approach may increase the risk of weight cycling, which is associated with numerous adverse health outcomes, including increased mortality risk and worsening of some cardiometabolic risk factors. For cardiometabolic risk factors, “+” denotes positive change (i.e., either ↑ or ↓ depending on the risk marker). See text for more information.

Figure 4.

CALERIE^™ studies of sustained calorie restriction (CR) in healthy adults without obesity. CALERIE^™ Phase 1 was designed as three single-site, randomized controlled trials (RCTs) conducted at Pennington Biomedical Research Center in Baton Rouge, LA; the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University in Boston, MA; and Washington University School of Medicine in St. Louis, MO. Duke Clinical Research Institute in Durham, NC served as the Coordinating Center. The interventions ranged from 6 months to 1 year and the prescribed level of CR was 20–30%, reflecting a reduction in energy intake of 20–30% below weight-maintenance energy needs. A total of 141 participants were enrolled. The favorable results across sites demonstrated the feasibility of CR and important benefits on numerous well-established cardiometabolic health indices (–149), supporting advancement to CALERIE^™ 2 (referred to as the CALERIE^™ trial), a multi-site, RCT with a 2-year CR intervention involving a 25% CR diet or and ad libitum control condition in 220 participants (150,151). The current CALERIE^™ Legacy study is an observation follow-up study of the same participants who participated in the CALERIE trial 10–15 years earlier and also includes a comparison group from the Baltimore Longitudinal Study of Aging.

Figure 5.

Exercise in both human and animal models has identified potential makers for exercise neuroprotection: Brain-derived neurotrophic factor (BDNF), irisin cathepsin B (CatB), vascular endothelial growth factor (VEFG), ketone bodies, and lactate have been documented to increase following exercise and are associated with increased neurogenesis, decreased neuroinflammation and improved cognition.

Figure 6.

A. The Problem: As humans have evolved, walking has become far more efficient, with a far lower calorie expenditure. B. In 1970 Monty Python’s Ministry of Silly walks comedic skit presented a putative solution to counter the increased efficiency of walking. At right is the actor and comedian John Cleese as Mr. Teabag demonstrating his iconic Silly Walk.

Figure 7.

A. Oxygen uptake (V̇O₂; ml · kg⁻¹ · min⁻¹) during participants’ usual walking (normal gait) and inefficient walking (Silly Walking, Mr. Teabag style) in 13 men and women (data from Gaesser et al. 242). For comparison, V̇O₂ during walking at 2.0 mph, 3.0 mph, and 4.0 mph in healthy adults (n = 40) is depicted by blue symbols (Data from Sawyer et al. 243) B. Association between energy expenditure (kcal/min; 1 kcal=4.18 kJ) and body mass (kg) for participants’ usual walking (dashed line) and the Mr. Teabag Silly Walking (solid line). Pearson correlations (r): participants’ usual walking (r=0.90); Mr. Teabag walk (r=0.81) (data from Gaesser et al. 242).