Circadian Rhythms and Their Impact on Aging PDF
|Author||S. Michal Jazwinski|
|File size||2.76 MB|
|Category||Cardiovascular,Free Medical Books|
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Aging is a function of the passage of chronological time, as the organism proceeds from birth to death. This simple statement does not account for the fact that individuals present differently as their chronological age progresses, and there is substantial heterogeneity among members of a birth cohort in the time of survival. For these reasons, the concept of biological age has been advanced, in recognition of this marked individual variation. Biological age takes into account the departure of any given individual from the population average in terms of time to death as well as function ability (Kim and Jazwinski 2015). Indeed, function ability, expressed in various ways, is used as a metric of biological age.
Given these considerations, biological aging can be defined as a progressive loss of function over time, in as much as such loss is characteristic of most individuals in the population. This loss of function occurs at many levels. The so-called ‘hallmarks of aging’ express this loss at the molecular and cellular levels, and they include genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication (Lopez-Otin et al. 2013). Except for the last, these hallmarks are entirely cell-autonomous. Intercellular communication, on the other hand, conjures up integrated function of the organism, to which the cell-autonomous hallmarks undoubtedly also contribute. Thus, we may consider biological aging to be the reflection of the loss of integrated function. At a clinical level, loss of integrated function leads to a degradation of robustness and resilience, such that biological aging is associated with an increase in the incidence of chronic disorders and susceptibility to acute diseases. These are often called the diseases and disorders of aging.
The circadian system has a period of about 24 hours, by definition. It assures that physiological processes are performed at the appropriate time of day or night. The circadian system is composed of a central clock in the suprachiasmatic nucleus (SCN) of the brain and peripheral oscillators in individual cells and tissues that operate in an autonomous fashion using similar core molecular components (Panda et al. 2002; Reppert and Weaver 2002; Froy and Miskin 2010). The central clock responds to light and dark (photoperiod), temperature, and nutritional status (feeding behavior). The resulting entrainment is signaled by autonomic connections or circulating hormones to the peripheral oscillators. Entrainment synchronizes central and peripheral clocks, without which the endogenous rhythms free run with a period of approximately 24 h. The circadian clock through peripheral circadian oscillators affects virtually every aspect of physiology and behavior, including metabolic activity and gene expression (Panda et al. 2002; Reppert and Weaver 2002; Froy and Miskin 2010). Expression of clock genes oscillates in almost all mammalian cells, and they regulate more than 10% of the human transcriptome (Peirson et al. 2006; Storch et al. 2002).
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