Graduation Date

5-2019

Document Type

Master's Thesis

Degree

Master of Science

Program

Biological Science

Program Director

Meredith Protas, PhD

First Reader

Pankaj Kapahi, PhD

Second Reader

Mary Sevigny, PhD

Abstract

Aging is accompanied by a progressive loss of circadian rhythms. Lifespan-extending dietary paradigms such as dietary restriction (DR) enhance circadian amplitude and appear to extend lifespan in a clock-dependent fashion. However, the mechanisms by which DR amplifies circadian rhythms and why circadian rhythms decline with age have yet to be fully elucidated. Here we find that DR amplifies circadian amplitude by enhancing light sensitivity in the eye. We performed a circadian mRNA microarray in flies (Drosophila melanogaster) reared on DR or a high nutrient diet and found that DR increases the number of circadian transcripts and selectively amplifies the expression and circadian amplitude of genes involved in the phototransduction signaling cascade (e.g. trp, trpL, inac, etc.). Flies reared on DR have an enhanced response to light and delayed age-related visual decline, as measured by positive phototaxis. DR's ability to enhance light sensing and delay age-related visual decline appears to require molecular clocks within the eye. We identified that DR-dependent enhancements in circadian amplitude, both in the head and body, require circadian light cycles: DR fails to enhance the circadian amplitude of the molecular clock when flies are kept in constant darkness. Circadian optogenetic depolarization of photoreceptor cells augments circadian activity rhythms, and rescues peripheral circadian amplitude in flies maintained on a high-nutrient diet. These findings suggest that DR promotes a positive feed-forward loop between the circadian clock and the phototransduction cascade to enhance circadian physiology and maintain eye health.

Available for download on Sunday, May 15, 2022

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