Calcineurin Inhibition Enhances Caenorhabditis elegans Lifespan by Defecation Defects-Mediated Calorie Restriction and Nuclear Hormone Signaling

Authors

Priyanka Das
Alejandro Aballay
Jogender Singh

Publication Date

11-1-2024

Journal

eLife

DOI

10.7554/eLife.89572

PMID

39485281

PMCID

PMC11530235

PubMedCentral® Posted Date

11-1-2024

PubMedCentral® Full Text Version

Post-print

Abstract

Calcineurin is a highly conserved calcium/calmodulin-dependent serine/threonine protein phosphatase with diverse functions. Inhibition of calcineurin is known to enhance the lifespan of Caenorhabditis elegans through multiple signaling pathways. Aiming to study the role of calcineurin in regulating innate immunity, we discover that calcineurin is required for the rhythmic defecation motor program (DMP) in C. elegans. Calcineurin inhibition leads to defects in the DMP, resulting in intestinal bloating, rapid colonization of the gut by bacteria, and increased susceptibility to bacterial infection. We demonstrate that intestinal bloating caused by calcineurin inhibition mimics the effects of calorie restriction, resulting in enhanced lifespan. The TFEB ortholog, HLH-30, is required for lifespan extension mediated by calcineurin inhibition. Finally, we show that the nuclear hormone receptor, NHR-8, is upregulated by calcineurin inhibition and is necessary for the increased lifespan. Our studies uncover a role for calcineurin in the C. elegans DMP and provide a new mechanism for calcineurin inhibition-mediated longevity extension.

Keywords

Animals, Caenorhabditis elegans, Longevity, Caenorhabditis elegans Proteins, Calcineurin, Signal Transduction, Caloric Restriction, Defecation, Receptors, Cytoplasmic and Nuclear, Calcineurin Inhibitors, Immunity, Innate, Basic Helix-Loop-Helix Transcription Factors, C. elegans

Published Open-Access

yes

Recommended Citation

Priyanka Das, Alejandro Aballay, and Jogender Singh, "Calcineurin Inhibition Enhances Caenorhabditis elegans Lifespan by Defecation Defects-Mediated Calorie Restriction and Nuclear Hormone Signaling" (2024). Faculty, Staff and Student Publications. 2482.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/2482