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Acupuncture and its modalities in the modulation of inflammaging: a scoping review of mechanisms, biomarkers, and clinical outcomes in chronic and degenerative diseases

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Abstract

This project consists of a scoping review aimed at mapping and synthesizing the available evidence on the effects of acupuncture and its modalities on inflammaging-related mechanisms, inflammatory biomarkers, and clinical outcomes in chronic and degenerative diseases associated with ageing. Population ageing is a major global public health challenge and is accompanied by an increasing prevalence of chronic and degenerative conditions, including osteoarthritis, sarcopenia, neurodegenerative diseases, vascular cognitive impairment, and other disorders associated with functional decline. A growing body of evidence indicates that many of these conditions share a common biological substrate known as inflammaging, a state of chronic, systemic, low-grade inflammation that develops progressively with advancing age. Inflammaging is characterized by persistent activation of inflammatory pathways, elevated levels of pro-inflammatory cytokines, immune dysregulation, and alterations in molecular mechanisms such as the NLRP3 inflammasome, NF-κB signaling, and p38 MAPK pathways. Acupuncture and its derived modalities have been increasingly investigated as potential non-pharmacological interventions capable of modulating inflammatory and neuroimmune processes. Experimental and clinical studies suggest that acupuncture may regulate inflammatory cytokines, influence immune cell activity, activate vagal anti-inflammatory pathways, and modulate molecular signaling pathways involved in chronic inflammation. However, the available evidence remains scattered across different diseases, populations, acupuncture modalities, and outcome measures, making it difficult to obtain a comprehensive understanding of its role in the modulation of inflammaging. The objective of this scoping review is to systematically identify, map, and synthesize the available evidence regarding the effects of acupuncture and its modalities on mechanisms and biomarkers related to inflammaging, as well as associated clinical outcomes in chronic and degenerative diseases linked to ageing. The review will consider human studies involving older adults and individuals with age-related chronic diseases, as well as experimental studies using animal models of ageing and senescence. The review will be conducted according to the methodological guidance of the Joanna Briggs Institute (JBI) and reported following the PRISMA Extension for Scoping Reviews (PRISMA-ScR). Searches will be performed in multiple electronic databases, including PubMed/MEDLINE, Embase, Scopus, Web of Science, and the Cochrane Library, as well as selected sources of grey literature. Eligible studies will include experimental, quasi-experimental, observational, and evidence synthesis studies investigating acupuncture modalities such as manual acupuncture, electroacupuncture, moxibustion, fire needling, needle-knife therapy, and related interventions. Data extraction will focus on study characteristics, participant characteristics, acupuncture intervention details, inflammatory biomarkers, molecular pathways, and clinical outcomes. Particular attention will be given to biomarkers and mechanisms associated with inflammaging, including cytokines such as IL-1β, IL-6, TNF-α, and IL-10, as well as pathways involving NLRP3 inflammasome activation, NF-κB signaling, p38 MAPK, and other relevant inflammatory and immunological processes. The expected outcomes of this project include: (1) a comprehensive mapping of the existing literature on acupuncture and inflammaging; (2) identification of the molecular mechanisms and inflammatory biomarkers most frequently investigated; (3) characterization of the acupuncture modalities and treatment protocols used across studies; (4) synthesis of reported clinical outcomes related to chronic and degenerative diseases associated with ageing; and (5) identification of knowledge gaps and research priorities for future experimental and clinical investigations. By providing an integrated overview of current evidence, this review is expected to contribute to a better understanding of the role of acupuncture in modulating age-related chronic inflammation and support the development of evidence-informed strategies aimed at promoting healthy ageing and improving the management of chronic degenerative diseases.