Abstract
The circadian clock system influences the biology of life by establishing circadian rhythms in organisms, tissues, and cells, thus regulating essential biological processes based on the day/night cycle. Circadian rhythms change over a lifetime due to maturation and aging, and disturbances in the control of the circadian system are associated with several age-related pathologies.However, the impact of chronobiology and the circadian system on healthy organ and tissue aging remains largely unknown. Whether aging-related changes of the circadian system’s regulation follow a conserved pattern across different species and tissues, hence representing a common driving force of aging, is unclear.Based on a cross-sectional transcriptome analysis covering 329 RNA-Seq libraries, we provide indications that the circadian system is subjected to aging-related gene alterations shared between evolutionarily distinct species, such as Homo sapiens, Mus musculus, Danio rerio, and Nothobranchius furzeri. We discovered differentially expressed genes by comparing tissue-specific transcriptional profiles of mature, aged, and old-age individuals and report on six genes (per2, dec2, cirp, klf10, nfil3, and dbp) of the circadian system, which show conserved aging-related expression patterns in four organs of the species examined. Our results illustrate how the circadian system and aging might influence each other in various tissues over a long lifespan and conceptually complement previous studies tracking short-term diurnal and nocturnal gene expression oscillations.
Highlights
The life of most organisms is, beyond other influences, controlled by two central biological events: Biological rhythms based on the timely regulation of physiological processes, and the biology of aging
Circadian rhythms (CRs)-related gene expression discriminates among species and tissues rather than age First, we evaluated the homogeneity of the analyzed transcriptomic data
We applied the tdistributed stochastic neighbor embedding (t-SNE) dimensionality reduction algorithm on the investigated RNA-Seq libraries based on the 46 selected CR-related genes
Summary
The life of most organisms is, beyond other influences, controlled by two central biological events: Biological rhythms based on the timely regulation of physiological processes, and the biology of aging. Circadian rhythms (CRs) are established by a genetically encoded circadian program, controlling a multitude of biological cycles and enabling an individual to adjust to periodic environmental changes during daytime, seasons, and lifetime. Its conserved nature allows to synchronize metabolic, endocrine, behavioral, and complex intracellular events across a 24-hour day/night cycle (for a recent review, see [1]). It is well established that aging interferes with the regulation of the circadian system, which, in return, contributes to the manifestation and progression of aging-related diseases (reviewed in [4, 5]). Ageindependent alterations of the circadian system can result in premature aging of vertebrates and invertebrates, suggesting a direct mutual interrelation between both processes [6]
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