title: The dynamic range of biologic functions and variation of many environmental cues may be declining in the modern age: implications for diseases and therapeutics.
abstract: 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. Loss of temporal variation of other hormones may contribute to biologic dysfunctions, especially those involving the hypothalamic-pituitary axis. Reduced variation of physical exertion, environmental stressors, and thermal gradients that characterize modern lifestyles may reduce the autonomic dynamic range resulting in lowered heart rate variability and a myriad of systemic dysfunctions. The health benefits of activities such as exercise, meditation, acupuncture, coitus, and laughter may operate through increasing autonomic variability. Reduced physical exertion also accounts for declining dynamic range of musculoskeletal function. The resulting muscle atrophy, fat infiltration, and sarcomere shortening may not only have deleterious local effects, but may also be involved in systemic metabolic dysfunctions such as insulin resistance. The extent to which our endogenous systems rely on environmental variation for self-tuning and the impact that under-utilization of compensatory mechanisms has on biologic function are not well understood. Modern therapeutic approaches generally result in reversion to the mean of physiologic functions and may buffer against variation. For example, beta-blockers are given to reduce adrenergic excess, insulin to treat insulin insufficiency, serotonin-reuptake inhibitors for depression, and refractive lenses for myopia. By undermining the demand for native compensatory functions, such therapeutic strategies may actually impair future ability to respond to biologic disequilibria. Generalizing from these observations, we anticipate benefits of therapeutic and lifestyle approaches that expand, rather than reduce, the dynamic range of many biologic experiences.
authors.affiliation: Department of Radiology, Stanford University, 470 University Avenue, Palo Alto, CA 94301, USA. ayun@stanford.edu
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Yun
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Bazar
authors.forename: Anthony
authors.initials: A
authors.lastname: Gerber
authors.forename: Patrick Y
authors.initials: PY
authors.lastname: Lee
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Daniel
mesh_terms: D000818:Animals; D001341:Autonomic Nervous System / Q000502:physiology; D001683:Biological Clocks / Q000235:genetics / Q000502:physiology; D002940:Circadian Rhythm / Q000235:genetics / Q000502:physiology; D004194:Disease; D004358:Drug Therapy; D004777:Environment; D014644:Genetic Variation; D006801:Humans; D008019:Life Style; D008550:Melatonin / Q000502:physiology; D008954:Models, Biological
chemical_list: D008550:Melatonin