Degree

Doctor of Philosophy (PhD)

Department

Biological Sciences

Document Type

Dissertation

Abstract

The development of therapies that can be applied in human health care to promote longer and healthier lives is one of the main goals of aging research. However, many of the interventions currently available have serious adverse effects that limit their translational potential. Thus, new strategies are urgently needed to promote healthy aging in humans. Here, we reveal a functional interaction between the insulin signaling pathway and mTOR pathway that promotes healthy aging in C. elegans via lysosomal tubulation. Their respective transcription factors, DAF-16/FOXO and HLH-30/TFEB cooperate, to drive the formation of tubular lysosomes (TLs) under various contexts, which contributes to systemic health benefits in late age. Remarkably, lysosomal tubulation in C. elegans can be triggered on demand by overexpressing  DrosophilaSVIP (dSVIP), a previously characterized and potent stimulator of TLs. Mechanistically, intestinal overexpression of dSVIP leads to nuclear accumulation of DAF-16 and HLH-30 in the gut and adjacent tissues and triggers global gene expression changes, including induction of vps-34 and related lipid-metabolism genes that contribute to tubular-lysosome activity. Collectively this work identifies a cellular process under the control of DAF-16 and HLH-30 that could be fine-tuned to develop therapies aimed at extending healthspan.

Date

3-12-2026

Committee Chair

Dr. Alyssa Johnson

LSU Acknowledgement

1

LSU Accessibility Acknowledgment

1

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