Regulation of lifespan and proteostasis by sensory neural activity and CaMK

The activity state of the nervous system can influence a wide variety of physiological processes, including lifespan. While the impact of neural activity on ageing and longevity remains a topic of debate, substantial evidence suggests that decreasing overall neural activity is linked to increased longevity in invertebrate and mammalian models. However, the specific neuronal groups and underlying mechanisms involved are not well understood. We investigated the role of the CaM kinase, cmk-1, in the nematode to address this knowledge gap. Strikingly, we found that the eliminating cmk-1 enhances lifespan and improves proteostasis by suppressing excitation in the thermosensory AFD neurons, particularly at elevated temperatures that trigger AFD hyperactivation. Furthermore, genetically reducing hyperactivation specifically in wild-type AFD neurons extends longevity and improves proteostasis, similar to the effects observed in cmk-1 mutant. These beneficial outcomes are attribute to the activation of DAF-16 in the intestine, likely through the release of the INS-1 neuropeptide from the thermosensory neural circuit. Our findings reveal a causal mechanism through which the activity of the sensory neural circuit regulates lifespan and proteostasis, highlighting the pivotal role of CaMK in shaping these processes by regulating neural activity.