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bioRxiv · 10.1101/2024.05.07.593041

Skin Collagen Actively Regulates the Aging of Cutaneous Sensory Neurons

Krishna, M.·Franitza, A. L.·E, L.
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Abstract

Despite advances in understanding molecular and cellular changes in the aging nervous system, the upstream drivers of these changes remain poorly defined. Here, we investigate the roles of non-neural tissues in neuronal aging, using the cutaneous PVD polymodal sensory neuron in Caenorhabditis elegans as a model. We demonstrate that during normal aging, PVD neurons progressively develop excessive dendritic branching, functionally correlated with age-related proprioceptive deficits. Our study reveals that decreased collagen expression, a common age-related phenomenon across species, triggers this process. Specifically, loss-of-function in dpy-5 or col-120, genes encoding cuticular collagens secreted to the epidermal apical surface, induces early-onset excessive dendritic branching and proprioceptive deficits. Adulthood-specific overexpression of dpy-5 or col-120 mitigates excessive branching in aged animals without extending lifespan, highlighting the specific role of these collagens in promoting neuronal healthspan. Notably, collagen reduction specifically drives excessive branching in select sensory neuron subclasses but does not contribute to dendritic beading, another aging-associated neurodegenerative phenotype distinctively associated with a different mechanosensitive dysfunction. Lastly, we identify that rig-3, an Immunoglobulin Superfamily member expressed in interneurons, acts upstream of collagen genes to maintain PVD dendritic homeostasis during aging, with downstream requirement of daf-16/FOXO. These findings reveal that age-related collagen reduction cues neuronal aging independently of collagens traditional structural support function, potentially involving bi-directional communication processes between neurons and non-neuronal cells. Our study also offers new insights into understanding selective neuron vulnerability in aging, emphasizing the importance of multi-tissue strategies to address the complexities of neuronal aging.

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Krishna, M., Franitza, A. L., E, L.. 2024-05-08. Skin Collagen Actively Regulates the Aging of Cutaneous Sensory Neurons. https://doi.org/10.1101/2024.05.07.593041

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