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      Circle(s) of Life: The Circadian Clock from Birth to Death

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      Biology
      MDPI AG

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          Abstract

          Most lifeforms on earth use endogenous, so-called circadian clocks to adapt to 24-h cycles in environmental demands driven by the planet’s rotation around its axis. Interactions with the environment change over the course of a lifetime, and so does regulation of the circadian clock system. In this review, we summarize how circadian clocks develop in humans and experimental rodents during embryonic development, how they mature after birth and what changes occur during puberty, adolescence and with increasing age. Special emphasis is laid on the circadian regulation of reproductive systems as major organizers of life segments and life span. We discuss differences in sexes and outline potential areas for future research. Finally, potential options for medical applications of lifespan chronobiology are discussed.

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          The Hallmarks of Aging

          Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. This deterioration is the primary risk factor for major human pathologies, including cancer, diabetes, cardiovascular disorders, and neurodegenerative diseases. Aging research has experienced an unprecedented advance over recent years, particularly with the discovery that the rate of aging is controlled, at least to some extent, by genetic pathways and biochemical processes conserved in evolution. This Review enumerates nine tentative hallmarks that represent common denominators of aging in different organisms, with special emphasis on mammalian aging. These hallmarks are: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. A major challenge is to dissect the interconnectedness between the candidate hallmarks and their relative contributions to aging, with the final goal of identifying pharmaceutical targets to improve human health during aging, with minimal side effects. Copyright © 2013 Elsevier Inc. All rights reserved.
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            Social jetlag: misalignment of biological and social time.

            Humans show large differences in the preferred timing of their sleep and activity. This so-called "chronotype" is largely regulated by the circadian clock. Both genetic variations in clock genes and environmental influences contribute to the distribution of chronotypes in a given population, ranging from extreme early types to extreme late types with the majority falling between these extremes. Social (e.g., school and work) schedules interfere considerably with individual sleep preferences in the majority of the population. Late chronotypes show the largest differences in sleep timing between work and free days leading to a considerable sleep debt on work days, for which they compensate on free days. The discrepancy between work and free days, between social and biological time, can be described as 'social jetlag.' Here, we explore how sleep quality and psychological wellbeing are associated with individual chronotype and/or social jetlag. A total of 501 volunteers filled out the Munich ChronoType Questionnaire (MCTQ) as well as additional questionnaires on: (i) sleep quality (SF-A), (ii) current psychological wellbeing (Basler Befindlichkeitsbogen), (iii) retrospective psychological wellbeing over the past week (POMS), and (iv) consumption of stimulants (e.g., caffeine, nicotine, and alcohol). Associations of chronotype, wellbeing, and stimulant consumption are strongest in teenagers and young adults up to age 25 yrs. The most striking correlation exists between chronotype and smoking, which is significantly higher in late chronotypes of all ages (except for those in retirement). We show these correlations are most probably a consequence of social jetlag, i.e., the discrepancies between social and biological timing rather than a simple association to different chronotypes. Our results strongly suggest that work (and school) schedules should be adapted to chronotype whenever possible.
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              Resetting of circadian time in peripheral tissues by glucocorticoid signaling.

              In mammals, circadian oscillators reside not only in the suprachiasmatic nucleus of the brain, which harbors the central pacemaker, but also in most peripheral tissues. Here, we show that the glucocorticoid hormone analog dexamethasone induces circadian gene expression in cultured rat-1 fibroblasts and transiently changes the phase of circadian gene expression in liver, kidney, and heart. However, dexamethasone does not affect cyclic gene expression in neurons of the suprachiasmatic nucleus. This enabled us to establish an apparent phase-shift response curve specifically for peripheral clocks in intact animals. In contrast to the central clock, circadian oscillators in peripheral tissues appear to remain responsive to phase resetting throughout the day.
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                Author and article information

                Contributors
                (View ORCID Profile)
                (View ORCID Profile)
                Journal
                BBSIBX
                Biology
                Biology
                MDPI AG
                2079-7737
                March 2023
                February 28 2023
                : 12
                : 3
                : 383
                Article
                10.3390/biology12030383
                36979075
                4be8e600-2514-4de2-b3a3-2b2a80c4db6c
                © 2023

                https://creativecommons.org/licenses/by/4.0/

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