Regulation of inflammaging

Abstract

The non-neuronal cholinergic system plays an important role in the modulation of immunity and in particular the control of the inflammatory response. The cholinergic anti-inflammatory pathway is mediated principally by the α7-nicotinic acetylcholine receptor (α7-nAChR) and its receptor-specific chaperone, resistance to inhibitors of cholinesterase (RIC)-3 chaperone protein. The point is made in this writing that therapeutic stimulation of the non-neuronal cholinergic system via, for instance, transcutaneous vagal stimulation, pharmaco-therapeutic activation of α7-nAChR/RIC-3, or stimulation of the pathway by other means, including microRNA treatment interventions could down-regulate states of inflammation such as the cytokines storm and chronic systemic inflammation in aging - viz, inflammaging. It is possible and even likely that controlling inflammaging by intervening on the non-neuronal cholinergic system (NNCS) will be beneficial to a wide range of aging-related diseases, from type 2 diabetes and obesity to periodontal disease.

Keywords: Acetylcholine (ACh); MicroRNAs (miRs); caspase activation and recruitment domain (CARD); cholinergic anti-inflammatory pathway (CHAIP); cyclic GMP-AMP synthase linked to a stimulator of interferon genes (cGAS-STING); host cell-associated damage-associated molecular patterns (DAMPs); inflammasome; leucine-rich repeat (LRR); metalloproteinase-8 (MMP8); non-neuronal cholinergic system (NNCS); nucleotide leucine-rich repeat-containing receptors (NLRs); nucleotide-binding oligomerization domain (NOD); pathogen-associated molecular patterns (PAMPs); pattern recognition receptors (PRRs); pyrin "cell death fold" (PYD) domain; resistance to inhibitors of cholinesterase-3 (RIC-3); α7 nicotinic acetylcholine receptor (α7-nAChR).