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Regulation of inflammaging.

Francesco Chiappelli1,2, Lily Fotovat3, Allen Khakshooy4

  • 1Dental Group of Sherman Oaks, Sherman Oaks, CA 91403.

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|July 10, 2025
PubMed
Summary
This summary is machine-generated.

Stimulating the non-neuronal cholinergic system can reduce inflammation and potentially treat aging-related diseases. This pathway, involving the alpha7-nicotinic acetylcholine receptor, offers a novel therapeutic target for conditions like inflammaging.

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)inflammasomeleucine-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) domainresistance to inhibitors of cholinesterase-3 (RIC-3)α7 nicotinic acetylcholine receptor (α7-nAChR)

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Area of Science:

  • Immunology
  • Neuroscience
  • Gerontology

Background:

  • The non-neuronal cholinergic system (NNCS) modulates immunity and inflammation.
  • The cholinergic anti-inflammatory pathway relies on the alpha7-nicotinic acetylcholine receptor (α7-nAChR) and RIC-3 chaperone.
  • Inflammaging, chronic inflammation in aging, contributes to age-related diseases.

Purpose of the Study:

  • To explore therapeutic strategies targeting the NNCS for inflammation control.
  • To investigate the potential of NNCS modulation in combating inflammaging and related diseases.

Main Methods:

  • Review of existing literature on the NNCS and cholinergic anti-inflammatory pathways.
  • Discussion of therapeutic interventions including transcutaneous vagal stimulation and pharmacotherapy.
  • Consideration of novel approaches like microRNA interventions.

Main Results:

  • Therapeutic stimulation of the NNCS can down-regulate inflammatory responses.
  • Targeting the α7-nAChR/RIC-3 complex is a key mechanism.
  • Interventions show promise in reducing cytokine storms and chronic inflammation.

Conclusions:

  • Modulating the NNCS offers a promising strategy to control inflammaging.
  • NNCS-based therapies could benefit a wide range of aging-related conditions, including diabetes, obesity, and periodontal disease.
  • Further research into NNCS interventions is warranted for age-related disease management.