Transient receptor potential ankyrin 1 (TRPA1) channels detect noxious cold and inflammatory mediators in mammals; yet their evolutionary origins and roles in neuro-immune integration remain unclear. Here, we investigated TRPA1 in Hydra vulgaris, an early metazoan with a simple nervous system, exposing polyps to noxious cold and Pseudomonas aeruginosa lysate. Using Western blotting, pharmacological modulation, and gene expression analyses, we demonstrated that TRPA1 mediates upregulation of nociceptive markers (Nrf2, NOS, SOD) and immune effectors (NF-κB, NOS, periculin, hydramacin). TRPA1 antagonism significantly reduced these responses, indicating its role as an amplifier of both nociceptive and innate immune signaling. These findings suggest that TRPA1-dependent coupling of nociceptive-like and immune responses is an ancient, conserved mechanism, providing insights into the molecular basis of integrated threat detection and offering potential avenues for targeting pain and inflammation-associated pathologies.

Organismal aging is not inevitable in multicellular animals, as early-branching metazoan lineages, such as cnidarians, display negligible senescence under defined conditions, despite conserved cellular pathways. Contrasting longevity phenotypes in Hydra species reveal distinct regulatory mechanisms underlying aging. A comparison between Hydra vulgaris and Hydra oligactis suggests that sustained telomerase activity, autophagy regulation, and microbiome stability in H. vulgaris are associated with stem cell renewal and long-term tissue homeostasis, whereas cold-induced stress in H. oligactis is accompanied by a disruption of these pathways, leading to rapid somatic decline, where autophagy dysfunction and microbiome dysbiosis may act as contributing or amplifying factors. Environmental sensing via conserved pathways may integrate these regulatory mechanisms. These observations suggest that aging in early-branching metazoans is a regulated, context-dependent process characterized by substantial lineage-specific variation rather than an inevitable, universal consequence of cellular senescence. Further mechanistic studies may provide evolutionary insights into longevity mechanisms and identify potential targets for modulating aging, although direct experimental validation remains necessary.