Circadian Rhythms and Their Impact on Aging

Abstract

This book examines the role of circadian rhythms in aging, an emerging area of biology. Although implicated in aging and longevity for over forty years, the richness of the ways in which the circadian system impacts aging has become evident only more recently. The circadian system consists of a central pacemaker and a multitude of peripheral clocks, located in most cells throughout the organism. These clocks keep metabolic, physiological, and behavioral patterns in tune with the twenty-four hour day/night cycle and with each other. Disruptions of the circadian system, such as the presence of light at night, can have profound pathological implications. The core circadian oscillator consists of a multicomponent transcriptional feedback loop that regulates the periodicity of expression of some ten percent of the genes in the human genome. This easily explains the broad influence of the circadian system. The chapters in this volume fall into four sections that follow a brief introduction. They are written by experts performing the research in this field. The first section/chapter surveys the operation of the aging circadian system with a focus on melatonin signaling. In the second section, this theme is amplified through a discussion of the aging lung, bone, and gastrointestinal system. A section composed of eight chapters explores in detail cellular and molecular mechanisms associated with circadian system aging, in a range of experimental models. The studies reviewed include genetic, epigenetic, molecular, cell biological, metabolic, and physiologic approaches. The final section details the effects of sleep disruption on mortality risk in older adults and the effects of physical activity on circadian rhythms in the elderly, adding to the earlier discussion of the potential of chronotherapeutics. Advanced undergraduates and graduate students will find this book both a suitable introduction and a definitive treatment of the impact of circadian rhythms on aging. Instructors and researchers in circadian biology and in aging biology will discover this to be a valuable reference work, which brings these fields into juxtaposition and merger. This volume will contribute to further advances in this important interdisciplinary area. ""Contents""; ""Introduction""; ""1 Circadian Dysregulation and Melatonin Rhythm Suppression in the Context of Aging""; ""Abstract""; ""1.1 Introduction""; ""1.2 Hallmarks of Aging: Effects of Melatonin""; ""1.3 Consequences of Disruption of Circadian Rhythms""; ""1.4 Cellular Aging: The Case of Stem Cell Senescence""; ""1.5 Circadian Disruption and Age-Related Diseases""; ""1.6 Concluding Remarks and Perspectives""; ""References""; ""2 Pulmonary Diseases, a Matter of Time""; ""Abstract""; ""2.1 Introduction""; ""2.2 Chronobiology of the Lung""; ""2.3 A Time for Pulmonary Diseases"" ""2.3.1 Chronic Obstructive Pulmonary Disease (COPD)""""2.3.2 Idiopathic Pulmonary Fibrosis (IPF)""; ""2.3.3 Obstructive Sleep Apnea (OSA)""; ""2.3.4 Infectious Disease and Vaccine Efficacy in the Elderly""; ""2.3.5 Lung Cancer""; ""2.3.6 Asthma""; ""2.4 The Circadian Clock Regulates the Markers of Aging. Implications for the Pathophysiology of Age-Related Lung Disease""; ""2.4.1 Telomere Attrition""; ""2.4.2 Genomic Instability""; ""2.4.3 Epigenetic Alterations""; ""2.4.4 Loss of Proteostasis""; ""2.4.5 Deregulated Nutrient Sensing""; ""2.4.6 Mitochondrial Dysfunction and Oxidative Stress"" ""2.4.7 Cellular Senescence""""2.4.8 Stem Cell Exhaustion""; ""2.4.9 Intercellular Communication""; ""2.5 Chrono-Therapy for Age-Related Lung Diseases""; ""2.6 Future Directions""; ""Acknowledgements""; ""References""; ""3 Circadian Regulation of Bone""; ""Abstract""; ""3.1 Introduction""; ""3.2 Circadian Rhythms and Bone""; ""3.2.1 Circadian Regulation of Clock Genes Expressed in Bone""; ""3.2.2 Circadian Regulation of Osteoblast- and Osteoclast-Specific Genes""; ""3.2.3 Mechanisms Underlying Clock-Mediated Regulation of Bone"" ""3.3 Humoral Effects of Bone Rhythms: Melatonin, Estrogen and Cortisol""""3.3.1 Melatonin Effects on Bone and Bone Rhythms""; ""3.3.2 Estrogen and Progesterone Effects on Bone and Bone Rhythms""; ""3.3.3 Cortisol Effects on Bone and Bone Rhythms""; ""3.3.3.1 Circadian Variation of Cortisol and Glucocorticoid Signaling in Bone""; ""3.3.3.2 Cortisol Effects on Clock Genes Expressed in Osteoblasts and Osteoclasts""; ""3.3.3.3 Effect of Lifestyle, Light Exposure and Environment on Cortisol Levels""; ""3.4 Strategies to Prevent Bone Loss Caused by Circadian Disruption""; ""References"" ""4 Aging and the Circadian Control of the Gastrointestinal System: From the Brain to the Gut Microbiome (and Back)""""Abstract""; ""4.1 Introduction""; ""4.2 Peripheral Circadian Clocks and the Gastrointestinal System""; ""4.3 Aging and Circadian Clocks""; ""4.4 Gastrointestinal Melatonin""; ""4.5 Aging, Circadian Rhythms, and the Gastrointestinal Microbiome""; ""4.6 Conclusion and Prospectus""; ""Acknowledgements""; ""References""; ""5 Circadian System and Aging in Rodent Models""; ""Abstract""; ""5.1 Introduction""; ""5.2 Mammalian Circadian System""