Circadian Rhythms and Their Impact on Aging

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 ofthe 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.

Auteur
S. Michal Jazwinski, Ph.D. is the John W. Deming, M.D. Regents Chair in Aging, Professor of Medicine, and Director of the Tulane Center for Aging at Tulane University. His research on various aspects of aging has been funded by the National Institute on Aging (NIH) and private foundations, and it spans over thirty years. It includes genetic studies in model organisms and multidisciplinary studies in humans. Victoria P. Belancio, Ph.D. is an Associate Professor of Structural and Cellular Biology at Tulane University. Her research on retrotransposon-associated genomic instability has been funded by the National Institute on Aging (NIH) and private foundations. It includes projects investigating how circadian disruption impacts DNA damage induced by retroelements and whether this damage influences mammalian aging.

Steven M. Hill, Ph.D. is the Edmond and Lily Safra Chair for Breast Cancer Research, Professor of Structural & Cellular Biology, and Director of the Tulane Center for Circadian Biology at Tulane University. His research on various aspects of circadian biology and breast cancer has been funded by the National Cancer Institute (NIH), the Army Department of Defense Breast Cancer Program, and private foundations, and spans over 25 years. His recent research efforts have focused on the impact of circadian/melatonin disruption by light at night on human breast cancer progression, metastasis, and drug resistance.

Résumé
Biological rhythms time the ebb and flow of virtually every physiological process, and their mutual coordination guarantees the integrity of the organism over space and time. Aging leads to the disintegration of this coordination, as well as to changes in the amplitude and/or frequency of the underlying rhythms. The results of this are accelerated loss of health during aging, and in experimental model systems curtailed lifespan occurs. This book will examine the machinery that constitutes circadian systems and how they impact physiologic processes. It will also discuss how disturbances of circadian rhythms can lead to complex diseases associated with aging. Much of this treatment will focus on metabolism and genome stability. Importantly, the chapters in this book will encompass work in several different models, in addition to human. The book will conclude with a discussion of modeling approaches to biologic cycles and chronotherapy, for future research and translation.

Contenu

Circadian dysregulation and melatonin rhythm suppression in the context of aging.- Pulmonary diseases, a matter of time.- Circadian regulation of bone.- Aging and the circadian control of the gastrointestinal system: from the brain to the gut microbiome (and back).- Circadian system and aging in rodent models.- The circadian system and aging of Drosophila.- Circadian control of mitochondrial dynamics.- Circadian rhythms and proteostasis in aging.- Circadian clocks and mTOR signaling.- Aging and the biological clock.- Developing circadian therapeutics against age-related metabolic decline.- The possible role of epigenetics in the memory impairment elicited by circadian rhythm disruption.- Circadian sleep-wake activity patterns during aging.- Effects of physical activity on circadian rhythms in the elderly.