VPS-34 INHIBITION AMELIORATES POSTURAL AGING BY REGULATING GABAERGIC MOTOR NEURON ACTIVITY IN C. ELEGANS - Abstract

Sep 29, 2026

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Motor aging involves multiple functional and postural changes, including slower movement and increased body stiffness and curvature, yet the neurobiological mechanisms and molecular pathways driving these phenotypes remain insufficiently understood. Using Caenorhabditis elegans as a model, aging worms showed reduced locomotor speed and increased curvature linked to altered neuromuscular junction activity. VPS-34 inhibition via PI3K VPS-34 mutation improved curvature defects by enhancing inhibitory GABAergic motor neuron activity, suggesting a protective mechanism for postural aging.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages2

Reading Time5 min

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Abstract

Model and phenotypes

Neural mechanisms at the neuromuscular junction

Role of VPS-34 inhibition and GABAergic activity

Innovation in Aging, 2025, Vol. 9, No. S2 749 Abstract citation ID: igaf122.2548 VPS-34 INHIBITION AMELIORATES POSTURAL AGING BY REGULATING GABAERGIC MOTOR NEURON ACTIVITY IN C. ELEGANS Xuhui Chen, Le Zhang, Shangbang Gao, and Cuntai Zhang, Huazhong University of Science and Technology, Wuhan, Hubei, China (People’s Republic) Motor aging encompasses various functional and postural phenotypes, including reduced movement speed and increased body stiffness and curvature. These phenotypes reflect physiological aging in multiple organs, such as bones (calcium loss, reduced collagen content and osteoporosis) and muscles (atrophy, decreased elasticity, reduced endurance and flexibility) . However, the 750 Innovation in Aging, 2025, Vol. 9, No. S2 neurobiological mechanisms regulating motor aging, particularly the specific molecular pathways and potential interventions, are not well understood. In this study, we used Caenorhabditis elegans to model motor aging. Aging worms exhibited reduced movement speed and increased body curvature, similar to human aging phenotypes. Investigations into synaptic morphology and neurotransmission function at C. elegans neuromuscular junction revealed that decreased excitatory motor neuron activity contributed to the reduction in movement speed. Notably, an imbalance between excitatory and inhibitory signaling resulted in the increased body curvature. Mutation of the phosphoinositide 3-kinase (PI3K) VPS-34, a key regulator of endosomal trafficking, alleviated the curvature defects associated with aging. This alleviation was linked to enhanced inhibitory GABAergic motor neuron activity, suggesting a protective role of VPS-34 inhibition in postural aging. Our findings demonstrate that different motor aging phenotypes are regulated by distinct neural mechanisms and VPS-34 regulates postural aging by modulating inhibitory motor neuron activity. These results thus offer new insights into VPS-34 inhibition as a potential neuro-intervention strategy for mitigating motor aging.

FAQs

What motor-aging phenotypes were observed in C. elegans?

Aging worms exhibited reduced movement speed and increased body curvature, mirroring key aspects of human motor aging phenotypes.

How did excitatory and inhibitory signaling relate to body curvature?

The study found an imbalance between excitatory and inhibitory signaling that contributed to the increased body curvature.

What effect did VPS-34 inhibition have on postural aging?

Mutation of PI3K VPS-34 alleviated age-associated curvature defects, and the improvement correlated with enhanced inhibitory GABAergic motor neuron activity.

Sep 29, 2026

Upload by Jake