MRNA-seq of ubiqutously and pan-neuronally reduce rpia-1 in Caenorhabditis elegans

ABSTRACT: Ribose-5-phosphate isomerase A (RPIA) is a rate-limiting enzyme, which connects oxidative phase to non-oxidative phase and mediates redox homeostasis in pentose phosphate pathway (PPP). Here, we report that spatially and temporally limited knockdown of rpia-1 prolongs lifespan and improves healthspan in C. elegans, reflecting the evolutionarily conserved phenotypes observed in Drosophila. We first confirmed that both ubiquitous (in N2) and pan-neuronal (in TU3401) knockdown of rpia-1 enhance tolerance to oxidative stress, reduce polyglutamine aggregation, and improve the deteriorated body bending rate caused by polyglutamine aggregation. Next, we observed that both rpia-1 knockdown conditions enhance lifespan. In addition, rpia-1 knockdown in glutamatergic or cholinergic neurons was sufficient to increase lifespan. Besides the regulation of healthspan through the elevation of NADPH levels, we also identified novel molecular mechanisms that contribute to the longevity effect. Our results showed that rpia-1 reduction was accompanied by induction of autophagic flux, activation of AMPK, and inhibition of TOR signaling. Importantly, the lifespan extension by rpia-1 knockdown required the activation of autophagy and AMPK pathways, and reduced TOR sig-naling. Moreover, the RNA-seq data from the two longlived rpia-1 knockdown strains supported our experimental findings and reveal potential downstream targets, which may play key roles in this intervention. Together, our data disclose the specific spatial and temporal conditions and the underlying molecular mechanisms of rpia-1 knockdown-mediated longevity in C. elegans. These findings may facilitate the development of translational medicine and the improvement of lon-gevity research.

ORGANISM(S): Caenorhabditis elegans

PROVIDER: GSE216697 | GEO | 2023/01/25

REPOSITORIES: GEO