Investigation of Environmental and Genetic Factors on Circadian Rhythm and Longevity

Studies of longevity and behavior have been facilitated by the genetically tractable model, Drosophila melanogaster (D. melanogaster). Disrupted circadian rhythms can be detrimental to health and lifespan by dysregulating the biological rhythms that guide behaviors such as sleeping and feeding. These stressors are associated with an increased risk for cancer and neurodegenerative diseases. Understanding how circadian biology is regulated by aging may inform novel interventions for age-related diseases. In this two-part study, we first characterize the lifespan of D. melanogaster under an extended light/dark cycle to determine whether dysregulated circadian rhythms affect longevity. The second study analyzes the effect of the longevity gene, methuselah (mth), on circadian periodicity. The mth mutant is a hypomorph with reduced mth expression, and flies harboring this mutation exhibit a ~35% prolonged lifespan. While the molecular mechanisms connecting aging and circadian biology remain unclear, our studies aim to understand if mth might influence the free-running clock and, if so, test whether this contributes to extended life. This study demonstrates how an extended light cycle can adversely affect longevity and the evidence that mth does not interfere with free-running clock rhythmicity.