Activating the vagus nerve-adrenal anti-inflammatory axis to delay aging: A randomized controlled trial protocol

Background: Aging is a primary risk factor for chronic diseases, yet safe and effective interventions remain limited. Traditional Chinese Medicine (TCM) highlights the role of acupuncture in health preservation, with ST36 (Zusanli) being a key acupoint for longevity. Preclinical studies suggest ST36 acupuncture modulates inflammation and oxidative stress, but robust clinical evidence is lacking. This trial aims to evaluate the efficacy of ST36 acupuncture in delaying aging and preventing age-related diseases through biomarkers and clinical outcomes. Methods: A single-center, randomized, single-blinded, controlled trial will enroll 120 healthy participants aged 45-70 years. Participants will be allocated to manual acupuncture, sham acupuncture, or blank control groups. The intervention involves 36 sessions over 12 weeks. Primary outcomes include aging biomarkers (DNA methylation, plasma cytokines) and 3D facial/thermal imaging for biological age estimation. Secondary outcomes assess quality of life (SF-36) and sleep quality (PSQI). Adverse events will be systematically documented. Discussion: This study will provide evidence on the anti-aging effects of ST36 acupuncture and its potential integration into preventive healthcare. Results may inform strategies to address global aging challenges and promote healthy longevity. Trial registration: Chinese Clinical Trial Registry ChiCTR2500101531. Registered on 27 April 2025.