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Cardiovascular behavioral medicine has significantly advanced the knowledge base regarding the mechanisms by which psychological and behavioral factors can impact cardiovascular function and has developed clear links between these factors and cardiovascular health and disease. More recent work has established numerous behavioral interventions that are efficacious, and in several cases demonstrated to be effective. However, despite these significant advances, translation to broad, real-world uptake and utilization has not been well studied, with consequential profound implications for health equity. The purpose of this article is to review what is known about effective implementation strategies to support the uptake of behavioral medicine interventions to improve cardiovascular health, to underscore the potential for developing additional implementation strategies for wide-scale uptake of effective cardiovascular behavioral medicine interventions, and to discuss the potential for developing additional implementation approaches while conducting early stage efficacy studies in this area. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
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Medicina de la Conducta , Terapia Conductista , Humanos , Ciencia de la ImplementaciónRESUMEN
Sleep deficiencies, which include insufficient or long sleep duration, poor sleep quality, and irregular timing of sleep, are disproportionately distributed among populations that experience health disparities in the United States. Sleep deficiencies are associated with a wide range of suboptimal health outcomes, high-risk health behaviors, and poorer overall functioning and well-being. This report focuses on sleep health disparities (SHDs), which is a term defined as differences in one or more dimensions of sleep health on a consistent basis that adversely affect designated disadvantaged populations. SHDs appear to share many of the same determinants and causal pathways observed for health outcomes with well-known disparities. There also appears to be common behavioral and biological mechanisms that connect sleep with poorer health outcomes, suggesting a link between SHDs and other health disparities observed within these designated populations. In 2018, the National Institute on Minority Health and Health Disparities, the National Heart, Lung, and Blood Institute, and the Office of Behavioral and Social Sciences Research convened a workshop with experts in sleep, circadian rhythms, and health disparities to identify research gaps, challenges, and opportunities to better understand and advance research to address SHDs. The major strategy to address SHDs is to promote integration between health disparity causal pathways and sleep and circadian-related mechanisms in research approaches and study designs. Additional strategies include developing a comprehensive, integrative conceptual model, building transdisciplinary training and research infrastructure, and designing as well as testing multilevel, multifactorial interventions to address SHDs.
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Trastornos Mentales , Sueño , Ritmo Circadiano , Disparidades en el Estado de Salud , Disparidades en Atención de Salud , Humanos , Factores de Riesgo , Estados Unidos/epidemiologíaRESUMEN
Recent discoveries demonstrate a critical role for circadian rhythms and sleep in immune system homeostasis. Both innate and adaptive immune responses - ranging from leukocyte mobilization, trafficking, and chemotaxis to cytokine release and T cell differentiation -are mediated in a time of day-dependent manner. The National Institutes of Health (NIH) recently sponsored an interdisciplinary workshop, "Sleep Insufficiency, Circadian Misalignment, and the Immune Response," to highlight new research linking sleep and circadian biology to immune function and to identify areas of high translational potential. This Review summarizes topics discussed and highlights immediate opportunities for delineating clinically relevant connections among biological rhythms, sleep, and immune regulation.
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Ritmo Circadiano/fisiología , Inmunidad , Sueño/fisiología , Animales , Diferenciación Celular , Ritmo Circadiano/inmunología , Educación , Humanos , Sistema Inmunológico , Microbiota/inmunología , National Institutes of Health (U.S.) , Sueño/inmunología , Linfocitos T , Estados UnidosRESUMEN
BACKGROUND: Dysfunctions in the serotonergic system have been implicated in several neurological disorders such as depression. Elderly individuals who have been diagnosed with clinical depression show elevated cases of neurodegenerative diseases. This has led to suggestions that modulating the serotonin (5-HT) system could provide an alternative method to current therapies for alleviating these pathologies. The neuroprotective effects of bilobalide in vitro have been documented. We aim to determine whether bilobalide affects the 5-HT system in the nematode C. elegans. The wild type worms, as well as well-characterized 5-HT mutants, were fed with bilobalide in a range of concentrations, and several 5-HT controlled behaviors were tested. RESULTS: We observed that bilobalide significantly inhibited 5-HT-controlled egg-laying behavior in a dose-dependent manner, which was blocked in the 5-HT receptor mutants (ser-4, mod-1), but not in the 5-HT transporter (mod-5) or synthesis (tph-1) mutants. Bilobalide also potentiated a 5-HT-controlled, experience-dependent locomotory behavior, termed the enhanced slowing response in the wild type animals. However, this effect was fully blocked in 5-HT receptor mod-1 and dopamine defective cat-2 mutants, but only partially blocked in ser-4 mutants. We also demonstrated that acetylcholine transmission was inhibited in a transgenic C. elegans strain that constitutively expresses Abeta, and bilobalide did not significantly affect this inhibition. CONCLUSION: These results suggest that bilobalide may modulate specific 5-HT receptor subtypes, which involves interplay with dopamine transmission. Additional studies for the function of bilobalide in neurotransmitter systems could aid in our understanding of its neuroprotective properties.
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Conducta Animal/efectos de los fármacos , Ciclopentanos/farmacología , Furanos/farmacología , Ginkgólidos/farmacología , Serotonina/farmacología , Factores de Edad , Aldicarb/farmacología , Péptidos beta-Amiloides/genética , Péptidos beta-Amiloides/metabolismo , Animales , Animales Modificados Genéticamente , Conducta Animal/fisiología , Caenorhabditis elegans , Proteínas de Caenorhabditis elegans/genética , Canales de Cloruro/genética , Inhibidores de la Colinesterasa/farmacología , Dopamina/farmacología , Relación Dosis-Respuesta a Droga , Humanos , Locomoción/efectos de los fármacos , Locomoción/genética , Mutación , Piperazinas/farmacología , Piridinas/farmacología , Receptores de Serotonina/clasificación , Receptores de Serotonina/genética , Reproducción/efectos de los fármacos , Reproducción/genética , Antagonistas de la Serotonina/farmacologíaRESUMEN
Despite the omnipresence of artificial and natural light exposure, there exists little guidance in the United States and elsewhere on light exposure in terms of timing, intensity, spectrum, and other light characteristics known to affect human health, performance, and well-being; in parallel, there is little information regarding the quantity and characteristics of light exposure that people receive. To address this, the National Center on Sleep Disorders Research, in the Division of Lung Diseases, National Heart, Lung, and Blood Institute, held a workshop in August 2016 on circadian health and light. Workshop participants discussed scientific research advances on the effects of light on human physiology, identified remaining knowledge gaps in these research areas, and articulated opportunities to use appropriate lighting to protect and improve circadian-dependent health. Based on this workshop, participants put forth the following strategic intent, objectives, and strategies to guide discovery, measurement, education, and implementation of the appropriate use of light to achieve, promote, and maintain circadian health in modern society.
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Ritmo Circadiano , National Heart, Lung, and Blood Institute (U.S.) , Fotoperiodo , Animales , Entorno Construido , Corazón/efectos de la radiación , Humanos , Ratones , Salud Pública , Sueño , Estados UnidosRESUMEN
Study Objectives: Social isolation has a multitude of negative consequences on human health including the ability to endure challenges to the immune system, sleep amount and efficiency, and general morbidity and mortality. These adverse health outcomes are conserved in other social species. In the fruit fly Drosophila melanogaster, social isolation leads to increased aggression, impaired memory, and reduced amounts of daytime sleep. There is a correlation between molecules affected by social isolation and those implicated in sleep in Drosophila. We previously demonstrated that acute sleep loss in flies and mice induced the unfolded protein response (UPR), an adaptive signaling pathway. One mechanism indicating UPR upregulation is elevated levels of the endoplasmic reticular chaperone BiP/GRP78. We previously showed that BiP overexpression in Drosophila led to increased sleep rebound. Increased rebound sleep has also been demonstrated in socially isolated (SI) flies. Methods: D. melanogaster were used to study the effect of social isolation on cellular stress. Results: SI flies displayed an increase in UPR markers; there were higher BiP levels, increased phosphorylation of the translation initiation factor eIF2α, and increased splicing of xbp1. These are all indicators of UPR activation. In addition, the effects of isolation on the UPR were reversible; pharmacologically and genetically altering sleep in the flies modulated the UPR. Conclusions: The reduction in sleep observed in SI flies is a cellular stressor that results in UPR induction.
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Drosophila melanogaster/citología , Drosophila melanogaster/metabolismo , Sueño/fisiología , Aislamiento Social , Estrés Fisiológico , Respuesta de Proteína Desplegada/fisiología , Animales , Proteínas de Unión al ADN/genética , Proteínas de Drosophila/genética , Drosophila melanogaster/efectos de los fármacos , Drosophila melanogaster/genética , Chaperón BiP del Retículo Endoplásmico , Factor 2 Eucariótico de Iniciación/metabolismo , Femenino , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Masculino , Fosforilación , Empalme del ARN , Transducción de Señal , Sueño/efectos de los fármacos , Sueño/genética , Respuesta de Proteína Desplegada/efectos de los fármacos , Respuesta de Proteína Desplegada/genética , Regulación hacia ArribaRESUMEN
Oxidative stress has been associated with both the aging process and the development of age-dependent tissue degenerative pathologies. Beneficial effects of antioxidant therapies to abrogate the deleterious consequences of elevated free radicals are implicated in disease prevention and cost-effective strategy. Previous data have shown protective effects of the polyphenol green tea constituent epigallocatechin gallate (EGCG) and a classic natural antioxidant alpha-lipoic acid (LA) against oxidative stress and aging. In this study, EGCG and alpha-lipoic acid were applied to model Caenorhabditis elegans, and their ability to modulate the life span and several age-associated behavioral declines were examined, including: pharyngeal pumping, chemotaxic behavior and amyloid beta-associated pathological behavior. It was demonstrated that both antioxidants attenuated the levels of hydrogen peroxide in C. elegans, but their effects on age-dependent decline in behaviors were different. EGCG, but not alpha-lipoic acid, attenuated the rate of decline in pharyngeal pumping behavior in C. elegans. In contrast, alpha-lipoic acid, but not EGCG, extended mean and maximal life span in C. elegans. Both EGCG and alpha-lipoic acid were able to facilitate the chemotaxis index and this effect was additive. Furthermore, EGCG, but not alpha-lipoic acid, moderately alleviated an Abeta-induced pathological behavior in a transgenic C. elegans strain. These results indicate that natural antioxidants can protect against age-dependent behavioral declines. Other protective mechanisms, in addition to their antioxidant properties, may underlie their differential beneficial effects on aging and physiological behaviors.
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Envejecimiento/psicología , Antioxidantes/farmacología , Caenorhabditis elegans/efectos de los fármacos , Catequina/análogos & derivados , Ácido Tióctico/farmacología , Péptidos beta-Amiloides/toxicidad , Animales , Catequina/farmacología , Quimiotaxis/efectos de los fármacos , Peróxido de Hidrógeno/metabolismo , Esperanza de Vida , Faringe/fisiologíaAsunto(s)
Trastornos del Sueño-Vigilia , Sueño , Femenino , Humanos , National Institutes of Health (U.S.) , Estados UnidosRESUMEN
Alterations in the quality, quantity, and architecture of baseline and recovery sleep have been shown to occur during aging. Sleep deprivation induces endoplasmic reticular (ER) stress and upregulates a protective signaling pathway termed the unfolded protein response. The effectiveness of the adaptive unfolded protein response is diminished by age. Previously, we showed that endogenous chaperone levels altered recovery sleep in Drosophila melanogaster. We now report that acute administration of the chemical chaperone sodium 4-phenylbutyrate (PBA) reduces ER stress and ameliorates age-associated sleep changes in Drosophila. PBA consolidates both baseline and recovery sleep in aging flies. The behavioral modifications of PBA are linked to its suppression of ER stress. PBA decreased splicing of X-box binding protein 1 and upregulation of phosphorylated elongation initiation factor 2 α, in flies that were subjected to sleep deprivation. We also demonstrate that directly activating ER stress in young flies fragments baseline sleep and alters recovery sleep. Alleviating prolonged or sustained ER stress during aging contributes to sleep consolidation and improves recovery sleep or sleep debt discharge.
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Envejecimiento/fisiología , Estrés del Retículo Endoplásmico/fisiología , Homeostasis/fisiología , Sueño/fisiología , Envejecimiento/genética , Animales , Conducta Animal/efectos de los fármacos , Conducta Animal/fisiología , Proteínas de Unión al ADN/metabolismo , Drosophila melanogaster , Estrés del Retículo Endoplásmico/efectos de los fármacos , Homeostasis/efectos de los fármacos , Chaperonas Moleculares/fisiología , Factores de Iniciación de Péptidos/metabolismo , Fenilbutiratos/farmacología , Desplegamiento Proteico , Transducción de Señal/fisiología , Sueño/efectos de los fármacos , Sueño/genética , Privación de Sueño/genética , Privación de Sueño/fisiopatología , Regulación hacia Arriba/efectos de los fármacosRESUMEN
Bivalve molluscs are newly discovered models of successful aging. Here, we test the hypothesis that extremely long-lived bivalves are not uniquely resistant to oxidative stressors (eg, tert-butyl hydroperoxide, as demonstrated in previous studies) but exhibit a multistress resistance phenotype. We contrasted resistance (in terms of organismal mortality) to genotoxic stresses (including topoisomerase inhibitors, agents that cross-link DNA or impair genomic integrity through DNA alkylation or methylation) and to mitochondrial oxidative stressors in three bivalve mollusc species with dramatically differing life spans: Arctica islandica (ocean quahog), Mercenaria mercenaria (northern quahog), and the Atlantic bay scallop, Argopecten irradians irradians (maximum species life spans: >500, >100, and ~2 years, respectively). With all stressors, the short-lived A i irradians were significantly less resistant than the two longer lived species. Arctica islandica were consistently more resistant than M mercenaria to mortality induced by oxidative stressors as well as DNA methylating agent nitrogen mustard and the DNA alkylating agent methyl methanesulfonate. The same trend was not observed for genotoxic agents that act through cross-linking DNA. In contrast, M mercenaria tended to be more resistant to epirubicin and genotoxic stressors, which cause DNA damage by inhibiting topoisomerases. To our knowledge, this is the first study comparing resistance to genotoxic stressors in bivalve mollusc species with disparate longevities. In line with previous studies of comparative stress resistance and longevity, our data extends, at least in part, the evidence for the hypothesis that an association exists between longevity and a general resistance to multiplex stressors, not solely oxidative stress. This work also provides justification for further investigation into the interspecies differences in stress response signatures induced by a diverse array of stressors in short-lived and long-lived bivalves, including pharmacological agents that elicit endoplasmic reticulum stress and cellular stress caused by activation of innate immunity.
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Bivalvos/genética , Daño del ADN , Longevidad/genética , Animales , Bivalvos/fisiología , FenotipoRESUMEN
The endoplasmic reticulum(ER) is a multifunctional organelle within which protein folding, lipid biosynthesis, and calcium storage occurs. Perturbations such as energy or nutrient depletion, disturbances in calcium or redox status that disrupt ER homeostasis lead to the misfolding of proteins, ER stress and up-regulation of several signaling pathways coordinately called the unfolded protein response (UPR). The UPR is characterized by the induction of chaperones, degradation of misfolded proteins and attenuation of protein translation. The UPR plays a fundamental role in the maintenance of cellular homeostasis and thus is central to normal physiology. However, sustained unresolved ER stress leads to apoptosis. Aging linked declines in expression and activity of key ER molecular chaperones and folding enzymes compromise proper protein folding and the adaptive response of the UPR. One mechanism to explain age associated declines in cellular functions and age-related diseases is a progressive failure of chaperoning systems. In many of these diseases, proteins or fragments of proteins convert from their normally soluble forms to insoluble fibrils or plaques that accumulate in a variety of organs including the liver, brain or spleen. This group of diseases, which typically occur late in life includes Alzheimer's, Parkinson's, type II diabetes and a host of less well known but often equally serious conditions such as fatal familial insomnia. The UPR is implicated in many of these neurodegenerative and familial protein folding diseases as well as several cancers and a host of inflammatory diseases including diabetes, atherosclerosis, inflammatory bowel disease and arthritis. This review will discuss age-related changes in the ER stress response and the role of the UPR in age-related diseases.
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Oxidative stress has been linked to various physiological and pathological processes such as aging and neurological disorders. Recent evidence has now implicated a role for oxidative stress in sleep and sleep loss. Studies suggest that wakefulness results in an oxidative burden and sleep provides a protective mechanism against these harmful effects. Prolonged wakefulness/sleep deprivation activates an adaptive stress pathway termed the unfolded protein response (UPR), which temporarily guards against the deleterious consequences of reactive oxygen species. The UPR affects the function of the endoplasmic reticulum, which is the site for integral and secretory membrane processing and folding. Several downstream effectors of the UPR operate in an antioxidant capacity to reduce the load of these toxic species; a process that may be important in delaying the progression of neurodegenerative diseases. This review will highlight the molecular components of the UPR that ameliorate the accumulation of oxidative stress and may therefore provide potential therapeutic targets.
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Antioxidantes/metabolismo , Privación de Sueño/metabolismo , Privación de Sueño/fisiopatología , Sueño/fisiología , Respuesta de Proteína Desplegada/fisiología , Animales , Retículo Endoplásmico/metabolismo , Retículo Endoplásmico/patología , Humanos , Estrés OxidativoRESUMEN
Alzheimer's disease (AD) is rapidly reaching epidemic proportions in the United States, currently affecting more than 5 million individuals and predicted to affect 14 million by 2050. Despite a general consensus that the amyloid-beta (Abeta) protein plays a significant role in disease progression, the underlying pathology of the disease is not entirely clear. Caenorhabditis elegans is a simple organism that has been used as a model for basic mechanistic studies on the underlying pathological processes involved in AD. Previous studies from our labs demonstrated that transgenic C. elegans with muscle specific expression of human Abeta undergo rapid paralysis, and worms with neuronal expression of Abeta show deficits in chemotaxis to volatile chemicals. In this study, we evaluate the effect of neuron specific expression of Abeta on multiple neuronally controlled behaviors in a transgenic C. elegans. These worms demonstrate deficits in odorant preference associative learning behavior, and the serotonin-controlled behaviors experience-dependent learning and egg laying. These newly identified learning-deficit behavioral phenotypes in the neuronal Abeta C. elegans suggest that the model may be used to elucidate underlying pathological events related to development of AD and for pharmaceutical intervention.