Chronic circadian disturbance by a shortened light-dark cycle increases mortality

Park, Noheon; Cheon, Solmi; Son, Gi Hoon; Cho, Sehyung; Kim, Kyungjin

doi:10.1016/j.neurobiolaging.2011.11.005

Cited by 58 publications

(51 citation statements)

References 39 publications

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“…In any case, the functional importance of clocks is attested by the numerous adverse effects of perturbing them on healthspan, both in insects [4–10] and rodents [11–16]. This ever-increasing list is consistent with the presence in all tissues of functional clocks, controlling up to 10% of the genes expressed in any given tissue [17].…”

Section: Introductionmentioning

confidence: 99%

Drosophila Clock Is Required in Brain Pacemaker Neurons to Prevent Premature Locomotor Aging Independently of Its Circadian Function

et al. 2017

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Circadian clocks control many self-sustained rhythms in physiology and behavior with approximately 24-hour periodicity. In many organisms, oxidative stress and aging negatively impact the circadian system and sleep. Conversely, loss of the clock decreases resistance to oxidative stress, and may reduce lifespan and speed up brain aging and neurodegeneration. Here we examined the effects of clock disruptions on locomotor aging and longevity in Drosophila. We found that lifespan was similarly reduced in three arrhythmic mutants (ClkAR, cyc0 and tim0) and in wild-type flies under constant light, which stops the clock. In contrast, ClkAR mutants showed significantly faster age-related locomotor deficits (as monitored by startle-induced climbing) than cyc0 and tim0, or than control flies under constant light. Reactive oxygen species accumulated more with age in ClkAR mutant brains, but this did not appear to contribute to the accelerated locomotor decline of the mutant. Clk, but not Cyc, inactivation by RNA interference in the pigment-dispersing factor (PDF)-expressing central pacemaker neurons led to similar loss of climbing performance as ClkAR. Conversely, restoring Clk function in these cells was sufficient to rescue the ClkAR locomotor phenotype, independently of behavioral rhythmicity. Accelerated locomotor decline of the ClkAR mutant required expression of the PDF receptor and correlated to an apparent loss of dopaminergic neurons in the posterior protocerebral lateral 1 (PPL1) clusters. This neuronal loss was rescued when the ClkAR mutation was placed in an apoptosis-deficient background. Impairing dopamine synthesis in a single pair of PPL1 neurons that innervate the mushroom bodies accelerated locomotor decline in otherwise wild-type flies. Our results therefore reveal a novel circadian-independent requirement for Clk in brain circadian neurons to maintain a subset of dopaminergic cells and avoid premature locomotor aging in Drosophila.

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Section: Introductionmentioning

confidence: 99%

Drosophila Clock Is Required in Brain Pacemaker Neurons to Prevent Premature Locomotor Aging Independently of Its Circadian Function

et al. 2017

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“…Circadian misalignment associated with aging has been implicated in the elevated risk of cancer (Reszka and Przybek, 2016, Smolensky et al, 2016b, Stevens, 2009), obesity (Gibson et al, 2009, Karatsoreos et al, 2011), diabetes (Kawakami et al, 2004, Spiegel et al, 2005), cardiovascular disease (Ha and Park, 2005, Kivimäki et al, 2006) and the onset of myocardial infarction and stroke (Malik et al, 1990, Scheer et al, 2009, Smolensky et al, 2016a, Tofler et al, 1987). Furthermore, circadian dysfunction accelerates cellular aging and mortality with period alterations shortening lifespan in animal models (Krishnan et al, 2012, Park et al, 2012). The decline in the robustness of the circadian system appears to arise earlier in peripheral tissues than the central brain (Gubin et al, 2016, Libert et al, 2012) underscoring the need for examination of circadian processes during middle age.…”

Section: Introductionmentioning

confidence: 99%

Aging and circadian dysfunction increase alcohol sensitivity and exacerbate mortality in Drosophila melanogaster

Nobrega

Mellers

Lyons

2017

Experimental Gerontology

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Alcohol abuse is a rising problem in middle-aged and older individuals resulting in serious health, family and economic consequences. Effective treatment necessitates the identification of factors influencing alcohol toxicity with aging. We investigated the interaction between aging, alcohol toxicity and circadian function using Drosophila as a model system. We found as wild type flies age, sensitivity to alcohol increases and circadian regulation of alcohol-induced behaviors weakens. Decreased circadian modulation is correlated with significantly greater alcohol sensitivity during the subjective day. The circadian clock modulates alcohol-induced mortality in younger flies with increased mortality following alcohol exposure at night. Older flies exhibit significantly longer recovery times following alcohol-induced sedation and increased mortality following binge-like or chronic alcohol exposure. Flies rendered arrhythmic either genetically or environmentally exhibit significantly increased alcohol sensitivity, longer recovery times and increased mortality. We hypothesize that the circadian clock phase specifically buffers behavioral and cellular alcohol sensitivity with this protection diminishing as the circadian clock weakens with age.

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“…The SCN itself and the paraventricular nucleus stay, however, locked to the LD cycle (Salgado-Delgado et al 2010). Desynchronization between clock and the LD cycle is thus unfavorable or even increases mortality (Park et al 2012).…”

Section: Significance Of Light and The Circadian Clock In Shift Work mentioning

confidence: 99%

How Light Resets Circadian Clocks

2014

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The daily revolutions of the earth around its axis are responsible for day and night and its annual orbit around the sun for the seasons with their fluctuations in day length. Most organisms have adapted to these diurnal and annual cycles. The strategies and mechanisms used are quite delicate and complicated.It came as a surprise that photosynthesis and many other processes are, however, additionally controlled by internal clocks. Thus, photosynthesis fluctuates not only during the daily light-dark cycle (=LD; see the List of Abbreviations and http://www.circadian.org/dictionary.html) but also when the plants are kept under LL and constant temperature (Hennessey and Field 1991). However, the period length (period for short) of this rhythmic event then deviates from exactly 24 h and is therefore called circadian (from Latin circa, about, and dies, day). If in the absence of LD and temperature cycles other 24 h time cues (also called zeitgeber, German for time giver) would control the rhythm, it should show an exact 24 h rhythm. This is not the case, demonstrating the endogenous nature of a clock that is locked to light signals (see Fig. 18.1). Spectrum of RhythmsEndogenous rhythms of organisms are not only tuned to the daily cycle of 24 h. The range of rhythms found in organisms covers ultradian (with periods of several hours to very short ones), circadian, and annual (with periods of about a year) rhythms. Other rhythms such as tidal, 14-day, and monthly ones cope with influences of the moon on the earth, mainly on the water movements of the oceans, and they are therefore found in organisms at the coasts and in the sea. Annual rhythms interact with the day-length changes during the year (see below). There are furthermore rhythms with periods covering several years. The following discussion of a "biological clock" is restricted to circadian rhythms. Even they are often not just composed of one clock type but form a "circadian system" consisting of two or more clocks with different prop- Function of Circadian ClocksThe term "clock" usually implies a time-measuring device or function. For instance, the day length (or night length) can be determined by an organism. Since day length is a function of the time of the year (long days in summer, short days in winter), it can be used to time certain events such as flowering or tuber formation of a plant or breeding of birds and mammals during the most appropriate season. These processes are denoted photoperiodism (see Chap. 19).However, a clock can also be used to set a certain temporal order. For instance, the circadian control of our sleepwake cycle ensures that we rise in the morning and fall asleep in the evening at a preferred time. Food intake and digestion are likewise controlled by this clock and gated to certain times of the day (Silver et al. 2011;Duguay and Cermakian 2009;Forsgren 1935). The circadian clock will time these events also under constant conditions. Furthermore, circadian clocks can serve as alarm clocks.

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Chronic circadian disturbance by a shortened light-dark cycle increases mortality

Cited by 58 publications

References 39 publications

Drosophila Clock Is Required in Brain Pacemaker Neurons to Prevent Premature Locomotor Aging Independently of Its Circadian Function

Drosophila Clock Is Required in Brain Pacemaker Neurons to Prevent Premature Locomotor Aging Independently of Its Circadian Function

Aging and circadian dysfunction increase alcohol sensitivity and exacerbate mortality in Drosophila melanogaster

How Light Resets Circadian Clocks

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