We hypothesize that declining dynamic range and variation of environmental cues may contribute to health dysfunctions, and that judicious expansion of biologic dynamic ranges may be beneficial. Three disparate examples involving the endocrine, autonomic, and musculoskeletal systems are discussed. Daytime sheltering, optical shading, and nighttime use of artificial light may reduce circadian luminal variation. The resulting melatonin alterations may contribute to systemic dysfunctions.

The influence of light on biologic functions in humans is not fully understood, but recent research points to a potentially significant role. As one of the master clocks in the body, melatonin secretion, mediated by photoperiod variations, regulates temporal variation of many core systems in the body including the autonomic, endocrine, and immune systems [5] and [8]. Melatonin dysfunctions have been implicated in a wide range of diseases involving these systems [9]. Light exposure is thought to regulate pineal function primarily through circadian retinal photoreceptors [10], most likely involving ganglion cells [11] and the suprachiasmatic nucleus [12]. Melatonin regulation through pathways independent of ocular photoexposure such as skin photoexposure has also been speculated [13], and bilirubin absorption of light is also thought to play a role in circadian entrainment [14]. Skin exposure to light also modulates the immune system [15].

In this context, the changing pattern of light exposure associated with modern lifestyles may be an under-recognized source of biologic dysfunction. In general, attributes of modern lifestyle, such as indoor vocations, daytime sheltering, eyeglasses that shade light, and nighttime use of artificial light may narrow the dynamic range of circadian light exposure. As a result, modern humans may experience less luminal contrast between daytime and nighttime compared to our biologic predecessors, and duration of light exposure per day may be longer. Evidence suggests that biologic dysfunctions may occur as a result. For instance, poor daytime lighting conditions in institutionalized elderly patients, as well as increased nighttime light exposure, have been implicated in melatonin dysfunction and sleep disorders [16]. Conversely, daytime luminescence therapy, which negatively regulates daytime melatonin, improves nighttime sleep, suggesting a possible rebound elevation of nocturnal melatonin function [16] and [17].

Heart rate variability (HRV), a measure of dynamic range of autonomic function, can decline under various circumstances and lead to an increased risk of cardiac events and mortality [21]. High HRV connotes robust strength of the sympathetic and parasympathetic response systems, as the interaction between these systems determines HRV [22]. Input variables that can produce a decline in HRV include aging, chronic stress, and lack of exercise [23] and [24].

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We see the loss of variation of stressor inputs as a major source of autonomic dysfunction and dampened HRV. It is intuitively appealing to speculate that everyday lives of our biologic predecessors may have been characterized by a substantially greater variation of stressors due to predatory forces and unpredictability of the environment. These stressors were probably acute in nature and spaced by stress-free periods. Modern humans have substantially altered their own environment such that acute stressors and environmental uncertainties including predation may have declined while background chronic stressors such as traffic, smog, and high-density living have emerged.

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echnological innovations such as heating and cooling systems, as well as the emergence of apparel, have dramatically narrowed the range of thermal experience among modern humans. Although these systems provide comfort, it is unclear to what extent they undermine long-term health by removing a fluctuating input signal to the autonomic system and by under-utilizing compensatory mechanisms.

Declining variation of physical exertion during the modern age may negatively impact health by promoting autonomic dysfunction. Intermittent physical exertion was likely an intrinsic part of everyday life among our biologic predecessors, and the modern reduction of physical exertion has been directly linked to reduced HRV, increased autonomic dysfunction, and many systemic illnesses [21]. While exercise may increase HRV through pathways independent of sympathetic stimulation, the evidence generally supports the assertion that exercise-associated intermittent sympathetic challenge is a key determinant of high HRV [22], [29] and [30]. Even a single episode of sub-maximal exercise can increase HRV and promote vagal function [30]. The reduced dynamic range of exertion may be a key component of the output dysfunctions related to the autonomic and metabolic systems. Our hypothesis suggests that exercise regimens that emphasize variation of speed, power, and type may produce the optimal, non-linear input pattern of signals for the autonomic system and generate robust improvements in HRV. The benefits of intermittent exercise may also be related to the variation of dynamic blood flow to muscle, which may be a key part of maintaining normal endothelial function [31].

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In addition to exercise, hot–cold baths, meditation, acupuncture, caffeine, alcohol, mood variation, stress variation, coitus, poetry reading, rhythmic breathing, crying, and laughter are among the many activities that may offer health benefits by challenging the autonomic system and expanding its dynamic range [32] and [33]. Laughter has been called “the best medicine” and the enhancement of HRV through intermittent acceleration of heart rate and respiration represents a plausible mechanism by which health benefits may accrue [32] and [33].

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Muscle stretching

In addition to dampening the dynamic range of the autonomic system, reduced physical exertion during modernity may also impair health by narrowing the kinesiologic range of the musculoskeletal system. It is well known that the range of motion (ROM) of many joints declines during aging [34]. The ROM of the jaw decreases with aging, independent of temporomandibular joint dysfunction [35]. The hip joint also demonstrates reduced ROM with advancing age [36].

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Whatever its inciting cause, reduced ROM elicits secondary changes, such as muscle atrophy, fatty deposition, and inhibition of protein synthesis, which may promote systemic disturbances [39], [41] and [42]. For instance, conversion of muscle, a large consumer of insulin and glucose, to adipose tissue can have undesirable metabolic consequences such as increased insulin resistance [43]. Indeed, computed tomographic evaluation of muscle composition suggests that fat content within muscles, which increases with aging, under-use, and decreased ROM [37], [38], [39] and [44], correlates strongly with systemic insulin resistance [45]. These concepts may help elucidate the unexplained improvement of diabetes among patients who participate in yoga [46], a form of exercise focused on muscle stretching. Sarcopenia could be an indicator of catabolic state, and may participate in the pathogenesis of many other systemic dysfunctions [47]. It appears that musculoskeletal dysfunction such as atrophy, loss of strength, imbalance, and joint pain associated with under-use or misuse may be independent contributing factors in the pathogenesis of osteoarthritis, which has traditionally been thought to result from accumulated structural damage [48].

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Empiric observation suggests that the perceived variation of many other environmental features may be potentially diminishing in modern times. For example, the foraging behaviors of many species follow circadian patterns and alternate between states of hunger and satiety, which are intertwined by a complex network of gut–brain hormones that also modulate metabolic function in reciprocal fashion [49]. It is unknown whether modern feeding patterns which reduce the dynamic range of hunger–satiety cycles, such as the extreme example of continuous 24-h feeding in the intensive care unit, are contributing to metabolic dysfunctions. Furthermore, while industrialization of the food industry has diversified the modern diet in some ways, nutrition may actually be becoming more homogeneous as processed foods become more ubiquitous.

We anticipate potential benefits from therapeutic and lifestyle approaches that expand, rather than reduce, the dynamic range of many biologic experiences.

Ironically, many current therapeutic approaches generally result in reversion to the mean of physiologic functions and may buffer against natural variations. For example, beta-blockers are given for adrenergic excess, serotonin reuptake inhibitors for serotonin pathway deficits, refractive lenses for myopia, and insulin for insulin insufficiency [24]. These approaches, augmenting a deficit and blocking an overactive pathway, may not only narrow the system dynamic range, but may also induce tachyphylaxis [24]. Perhaps a paradoxical approach which expands the biologic dynamic range and relies on compensatory mechanisms, rather than drug effects, may be useful in the treatment of diseases [24]. The ideal solution may involve asynchronous or alternating administration of drugs that have opposing mechanisms to widen the dynamic range and strengthen compensatory mechanisms in both directions. Thoughtful integration into native chronobiologic patterns may be necessary. The goal is to enable eventual withdrawal of all drugs while restoring the normal dynamic range of physiologic functions.

Beyond individuals, the dynamic range of parameters at the population level may also be changing during modern times. Since the advent of mass transportation, a global melting pot has emerged and the variation of human genotypes and phenotypes may be declining. Modern trends in agriculture have narrowed the genotypic variation of many plant species. Whereas speciation enables greater genotype variation in a population over time through reproductive isolation, extinction of species (de-speciation) that occurs as humans overrun natural habitats may be contributing to an earth-wide loss of genotypic dynamic range. Advances in telecommunications have enabled unprecedented sharing of knowledge, but the collective dynamic range of esoteric ideas and skills that had accrued over thousands of years of human evolution may be declining with the emergence of a global information consensus.