# Repeated activation of Gαq has a detrimental impact on C. elegans in an age-dependent manner

## TL;DR

Repeated activation of Gαq in C. elegans harms the worms more as they age, affecting stress granules and recovery.

## Contribution

This study reveals age-dependent effects of Gαq/PLCβ activation on stress granule dynamics and recovery in C. elegans.

## Key findings

- Single Gαq activation slightly increases lifespan in young C. elegans.
- Repeated activation leads to stress granule accumulation in middle-aged worms.
- Older worms show reduced stress granule dynamics and unresponsiveness to Gαq activation.

## Abstract

Gαq mediates signals from neurotransmitters to transduce calcium signals through the activation of phospholipase Cβ (PLCβ). In cultured neuronal cells, Gαq stimulation causes two different effects: a calcium-dependent retraction of neurites that requires PLCβ activity and a promotion of stress granules that sequester ATP5f1b that is independent of PLCβ activity. Here, we have investigated the effect of single and repeated activation of the Gαq/PLCβ pathway in young (Day 1), middle-aged (Day 4), and old (Day 8) Caenorhabditis elegans. While single activation has a slight increase in lifespan, repeated activation is detrimental. Worms that lack PLCβ show high mortality and indicate a need for calcium signaling in early adulthood. Using a combination of fluorescence imaging methods, we followed stress granule formation mediated by activation of Gαq/PLCβ. We find that activation of young worms does not cause the formation of stable stress granules that sequester ATP51fbl, but middle-aged worms assemble these stress granules. Disassembly of these particles is slow enough that repeated activation causes their accumulation. Older worms show a severely slowed stress granule dynamic and are largely unresponsive to Gαq/PLCβ activation in terms of stress granule assembly, locomotion, neuronal calcium signaling, and morphological recovery upon stimulation. Taken together, our studies show that PLCβ-mediated mechanisms in young worms are robust but progressively decline with age, which may lead to the accumulation of intracellular aggregates and reduced ability to be stimulated by neurotransmitters and recover after neurotransmitter stimulation.