BioProject

As global life expectancy continues to increase, shifting our focus from solely extending lifespans to actively pursuing healthy ageing is crucial. More...

As global life expectancy continues to increase, shifting our focus from solely extending lifespans to actively pursuing healthy ageing is crucial. GSTA1-3 members of the alpha class of glutathione S-transferase are involved in diverse biological processes, including metabolism and immune regulation, indicating their influence on human health and lifespan. We used Caenorhabditis elegans as a model organism to examine the impact of gst-35, an orthologous gene of mammalian GSTA1, GSTA2, and GSTA3, on healthy ageing. Our findings indicated that gst-35 overexpression had deleterious effects on various physiological aspects of nematodes. The overexpression specifically caused a significant reduction in nematode lifespan, inhibited nematode development and growth, and substantially diminished reproduction, physical fitness, and stress resistance. Conversely, gst-35 knockout in nematodes showed a partial improvement in physical fitness and stress resistance. Comprehensive RNA-sequencing transcriptome analysis revealed that gst-35 overexpression perturbed metabolic homeostasis. Additionally, gst-35 overexpression induceds lysosomal dysfunction via pmk-1 and skr, affecting the process of healthy ageing. These findings unravel the intricate role of gst-35 in the ageing process, contributing to the expanding knowledge in the field of healthy ageing research. Overall design: To investigate the specific mechanism by which gst-35 affects the health cycle of nematodes, we used N2, PHX6971 (knockout), and PHX7528 (overexpression) nematode strains to detect changes in gene transcription levels on the fifth day of adult nematodes. Less...