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Tracking Our Physical Inactivity and Progression to Death: Is This Evolutionary Stagnation?

Progression is rarely linear. Once highly mobile hunters and gatherers, we have evolved into a technologically advanced but kinetically stagnant species. Sedentary societies define today's cultural norms (1). The adverse health outcomes associated with sedentary behavior have led many to conclude that sedentary behavior is a novel risk factor whose population-attributable risk may even surpass that of smoking (2). Others have interpreted such associations more cautiously, given inconsistencies in evidence across studies, measurement biases, residual confounding, ambiguity in explanatory intercausal pathway mechanisms, and the absence of clinical trials that are adequately powered to detect differences in mortality from sedentary interventions (3). With this context in mind, we read Diaz and colleagues' study (4). This prospective cohort study tracked 7985 U.S. adults aged 45 years or older (a subgroup of the REGARDS [Reasons for Geographic and Racial Differences in Stroke] study) over a median follow-up of 4 years. The study showed a strong doseresponse relationship between daily volume of sedentary behavior and all-cause mortality, even after adjustment for many baseline factors, including moderate to vigorous physical activity. The report builds on the existing literature in several ways. First, the authors incorporated objective accelerometer data, thereby addressing methodological limitations of previous research, which often relied on self-reporting to estimate sedentary time. Second, the authors used risk adjustment to quantify the incremental effect of various factors on associations between sedentary time and mortality. In so doing, they demonstrated, for example, that adjustments for moderate physical activity attenuated but did not negate the association between sedentary time and mortality. Third, many sensitivity analyses were done, including 1 that quantified the potential effect of unmeasured confounders on their findings. In short, Diaz and colleagues' study was methodologically rigorous and their findings robust. Arguably, however, this study's most important contribution involved disentangling 2 nonmutually exclusive sedentary behavioral patterns: total daily sedentary time and uninterrupted sedentary bout duration. By exploring joint associations, the authors showed that how sedentary time is accrued affects associations between sedentary time and mortality. Persons with uninterrupted sedentary bouts of 30 minutes or more had the highest risk for death if total sedentary time also exceeded 12.5 hours per day. Conversely, in those whose daily sedentary volumes were low, uninterrupted bout lengths had little if any associated effects on mortality. In sum, Diaz and colleagues showed that excessive sedentary behavior is bad and even worse if such behavior is accrued in lengthy, uninterrupted bouts throughout the day. The mechanisms by which sedentary behavior is associated with adverse health outcomes remain unclear and complex. Hypotheses have focused on cardiometabolic pathways and have ranged from alterations in the genetic expression of energy metabolism to reductions in insulin sensitivity, net calorie expenditure, and increased adiposity (5). Although their trial was not designed to elucidate mechanisms, Diaz and colleagues' results support the emerging hypothesis that the physiologic mechanisms underlying the health benefits of physical activity may be distinct from the deleterious health consequences of sedentary behaviors (3). The high mortality associated with prolonged, uninterrupted sedentary bouts also reaffirms the potential importance of skeletal muscle inactivity on cardiometabolic pathway mechanisms (6). If we are to conclude that sedentary behavior is a novel risk factor, what are the potential solutions? Sitting less and moving more seems like an appropriate start, but severing cultural norms may be easier said than done. Some have advocated for modifications to the built environment, which may promote walkability and leisure time physical activity. However, targeting only that environment will likely be insufficient, because individual variations will still exist (7). A more personalized approach may therefore be required. Historically, many individual-level interventions have focused on promoting moderate to vigorous physical activity, on the assumption that exercise might indirectly reduce sedentary time. However, evidence would suggest otherwise. Reductions in sedentary time seem best achieved through interventions that specifically promote sedentary behavior avoidance rather than promoting exercise alone or a mixture of exercise and sedentary activities (8). In this regard, Diaz and colleagues' recommendation to limit sedentary episodes to fewer than 30 minutes at a time has face validity. Yet not all physical activity behaviors yield similar effects on mortality. For example, evidence has shown strong correlations among exercise intensity, cardiopulmonary fitness, and survival (9). Accordingly, time-reallocation interventions have gained interest in the literature, whereby daily sedentary time is substituted with various physical activities to optimize survival (3). Although the effectiveness of sedentary interventions awaits future research, one thing is almost certain: All interventions, regardless of composition, will likely require self-regulatory skills that facilitate tracking movement patterns and monitoring daily physical activity (and inactivity) behaviors to optimize self-management and outcomes (10). Observational studies, no matter how well-designed, cannot imply causality. The current study is no exception. Misclassification biases may have existed despite the use of accelerometers, and no degree of risk adjustment can remove the possibility of residual confounding. That said, Diaz and colleagues advance our understanding of sedentary behaviors and their associated effects on mortality. Daily sedentary time, uninterrupted sedentary bout length, and moderate to vigorous physical activity may each play an important and distinct role in long-term health behaviors and survival. Interventions with the greatest effect on population outcomes may be those that take each into account. Such interventions may require us to count the total number of hours we are sedentary per day, the total number of minutes we sit at a time, the total number of standing breaks we take per hour, the total number of steps we take per day, and the total metabolic equivalent of taskminute volume of exercise we achieve per week. Yikes! That sure is a lot of counting over the course of a lifetimeall to reverse the evolutionary patterns of a society gone lazy. Might it not just be easier to return to our origins as hunters and gatherers?