4.6 Article

Age-dependent expression changes of circadian system-related genes reveal a potentially conserved link to aging

Journal

AGING-US
Volume 13, Issue 24, Pages 25694-25716

Publisher

IMPACT JOURNALS LLC

Keywords

aging; circadian clock system; circadian rhythm; inter-species comparison; longevity; RNA-Seq

Funding

  1. 'Else-KronerFresenius-Stiftung' (EKFS)
  2. Deutsche Forschungsgemeinschaft (DFG, German Research Foundation-Clinician Scientist-Program OrganAge) [WI 830/12-1]
  3. Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) [MA5082/15-1]
  4. Ministry for Economics, Sciences and Digital Society of Thuringia (TMWWDG) [RegenerAging-52-5581-413-FSU-I-03/14, RegenerAging-52-5581-413-FSU-I-03/15, DigLeben-5575/10-9]
  5. Interdisciplinary Center for Clinical Research of the Medical Faculty Jena [FF01, MSP09]

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Research indicates that the circadian clock system is influenced by aging-related gene alterations across different species and tissues, showing consistent aging-related expression patterns. These findings help to elucidate how the circadian system and aging interact with each other and why this interaction is crucial during a long lifespan.
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 (pert, 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.

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