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Updated: May 26, 2026
Circadian Entrainment of Drosophila Melanogaster
Published on: June 3, 2020
Effects of aging on the molecular circadian oscillations in Drosophila
Kuntol Rakshit1, Natraj Krishnan, Elżbieta M Guzik
1Department of Zoology, Oregon State University, Corvallis, Oregon 97331, USA.
Abstract:
Circadian clocks maintain temporal homeostasis by generating daily output rhythms in molecular, cellular, and physiological functions. Output rhythms, such as sleep/wake cycles and hormonal fluctuations, tend to deteriorate during aging in humans, rodents, and fruit flies. However, it is not clear whether this decay is caused by defects in the core transcriptional clock, or weakening of the clock-output pathways, or both. The authors monitored age-related changes in behavioral and molecular rhythms in Drosophila melanogaster. Aging was associated with disrupted rest/activity patterns and lengthening of the free-running period of the circadian locomotor activity rhythm. The expression of core clock genes was measured in heads and bodies of young, middle-aged, and old flies. Transcriptional oscillations of four clock genes, period, timeless, Par domain protein 1ϵ, and vrille, were significantly reduced in heads, but not in bodies, of aging flies. It was determined that reduced transcription of these genes was not caused by the deficient expression of their activators, encoded by Clock and cycle genes. Interestingly, transcriptional activation by CLOCK-CYCLE complexes was impaired despite reduced levels of the PERIOD repressor protein in old flies. These data suggest that aging alters the properties of the core transcriptional clock in flies such that both the positive and the negative limbs of the clock are attenuated.
Insights
Aging disrupts fruit fly circadian clocks, impairing core clock gene transcription in heads. This suggests aging weakens both positive and negative regulatory pathways of the circadian transcriptional clock.
Area of Science:
- Chronobiology
- Molecular Biology
- Aging Research
Background:
- Circadian clocks regulate daily rhythms essential for temporal homeostasis.
- Age-related decline in output rhythms like sleep-wake cycles is observed across species.
- The precise cause of this decline—core clock defects versus weakened output pathways—remains unclear.
Purpose of the Study:
- To investigate age-related changes in behavioral and molecular rhythms in Drosophila melanogaster.
- To determine if aging affects the core transcriptional clock or clock-output pathways.
Main Methods:
- Monitoring of age-related changes in rest/activity patterns and circadian locomotor activity.
- Measurement of core clock gene expression (period, timeless, vrille, Par1) in fly heads and bodies at different ages.
- Analysis of Clock and cycle gene expression and their regulatory function.
Main Results:
- Aging flies exhibited disrupted rest/activity patterns and a lengthened circadian period.
- Significant reduction in transcriptional oscillations of key clock genes (period, timeless, vrille, Par1) was observed in heads, but not bodies, of aging flies.
- Impaired transcriptional activation by CLOCK-CYCLE complexes occurred despite reduced PERIOD repressor levels in older flies.
Conclusions:
- Aging in fruit flies leads to defects in the core transcriptional clock.
- Both positive and negative regulatory limbs of the circadian clock are attenuated with age.
- These findings suggest a fundamental alteration in the molecular clockwork mechanism during aging.
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