The aging clock: circadian rhythms and later life
Suzanne Hood, Shimon Amir
Suzanne Hood, Shimon Amir
Published February 1, 2017
Citation Information: J Clin Invest. 2017;127(2):437-446. https://doi.org/10.1172/JCI90328.
View: Text | PDF
Review

The aging clock: circadian rhythms and later life

Abstract

Circadian rhythms play an influential role in nearly all aspects of physiology and behavior in the vast majority of species on Earth. The biological clockwork that regulates these rhythms is dynamic over the lifespan: rhythmic activities such as sleep/wake patterns change markedly as we age, and in many cases they become increasingly fragmented. Given that prolonged disruptions of normal rhythms are highly detrimental to health, deeper knowledge of how our biological clocks change with age may create valuable opportunities to improve health and longevity for an aging global population. In this Review, we synthesize key findings from the study of circadian rhythms in later life, identify patterns of change documented to date, and review potential physiological mechanisms that may underlie these changes.

Authors

Suzanne Hood, Shimon Amir

×

Figure 1

The molecular circadian clock.

Options: View larger image (or click on image) Download as PowerPoint
The molecular circadian clock. Heterodimers of the transcription factors...
Heterodimers of the transcription factors BMAL1 and CLOCK upregulate the expression of many target genes. Of these, the protein products of the Period (Per) and Cryptochrome (Cry) genes provide a feedback mechanism to inhibit the transcriptional activity of CLOCK-BMAL1. The activity of PER-CRY dimers is regulated at a posttranscriptional level via phosphorylation by kinases, including casein kinase 1ε (CKI). Other gene targets of CLOCK-BMAL1 include the nuclear receptors retinoid-related orphan receptor α (RORα) and REV-ERBα, which, respectively, promote and inhibit the transcription of Bmal1. In addition to these core components of the genetic clock, CLOCK-BMAL1 regulates the expression of a number of downstream targets that are referred to as clock-controlled genes (CCGs) (13, 14) P, phosphorylation.