The Effects of a Disrupted Circadian Rhythm on C. Elegans Longevity and Egg Laying

Overview

Circadian rhythms exert broad control over the physiology and behavior of most organisms. These include intermediary metabolism, immune function, neuro-endocrine function, sleep-wake cycles, and optimal physical and mental productivity. Disruption of circadian rhythms is linked to abnormal behavior, increased disease risk, and reduced life span. The primary regulator, or zeitgeber (time-giver), for circadian rhythms is light. This investigation reports the effects of a disrupted circadian rhythm on the lifespan and egg-laying of the nematode C. elegans. Four groups were used: 1) a control group of wild type N2 worms exposed to 12h of light/12h of dark per day; 2) a long day (LD) group of wild type N2 worms exposed to 24h of light/0h of dark per day; 3) a long day hif-1 mutant worm group (LD-h) exposed to 24h of light/0h of dark per day; and 4) a long day group of N2 worms with an artificial insulin cycle (LD-i). Mutant hif-1 worms in the LD-h test group were used because hif-1 is a homolog of a human circadian gene associated with lipid metabolism and diabetes. The secretion of insulin in humans follows a circadian rhythm with higher daylight levels. The artificial insulin cycle in the LD-i test group was employed to test the effects of providing an additional zeitgeber, which the worms could in-turn use to adjust their circadian clock. All worms were entrained by a 12-hour light, 12-hour dark cycle for 3 days. Following the entrainment period, test groups were exposed to a continuous 24-hour daylight period. During the entrainment period, egg-laying followed a circadian cycle with more eggs laid during light hours than dark hours. Following the natural life cycle of C. elegans, egg production stopped after the 3-day entrainment period. Circadian rhythm disruption decreased the median lifespan of wild type C. elegans by 20.0%. The addition of insulin in the LD-i group decreased the negative effects of a disrupted circadian rhythm by 7 percentage points, resulting in a decreased median lifespan of 13%. Down regulation of the hif-1 gene increased the negative effects of a disrupted circadian rhythm by 13 percentage points, resulting in a decreased median lifespan of 33%. These results demonstrate that disruption of the circadian rhythm negatively affects health in C. elegans. These responses are exacerbated by changes in circadian gene expression and can be counteracted by additional circadian clock regulators, such as exogenous insulin.

Competition history

• AJAS 2019 Category not listed

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