Non-pharmaceutical interventions and epigenetic aging in adults: Protocol for a scoping review

Introduction: Aging is the strongest risk factor for most chronic diseases. The rising burden of an aging population and non-communicable diseases (NCDs), contributes to escalating costs for society. Several non-pharmaceutical interventions can lower the risk of NCDs, including common mental disorders (CMDs), and may slow down biological aging, as evidenced by outcome markers such as epigenetic clocks. However, a comprehensive overview of whether and which non-pharmaceutical interventions may impact human epigenetic aging is missing. Synthesizing evidence of interventions on epigenetic aging that can be adopted by a wider population is key to guide healthy aging initiatives and to reduce the burden of NCDs and CMDs. This scoping review will identify and assess non-pharmaceutical interventions aimed to slow down epigenetic aging, including their intervention components, and the mode used for intervention delivery. Methods and analysis: This protocol will include single- and multicomponent intervention studies that target individuals ≥ 18 years of age and use epigenetic clocks as primary or secondary outcomes. Five electronic databases will be searched for studies between July 2011 until December 2023. The final search will include the search terms adults, non-pharmaceutical interventions, epigenetic aging and their respective synonyms. We will include randomized controlled trials, non-randomized controlled studies, cohort studies, and case-control studies. Additionally, the reference list of other reviews will be screened for relevant articles. Study selection is carried out based on the defined eligibility criteria by two authors. Quality and risk of bias for the included studies will be assessed using the Critical Appraisal Skills Programme (CASP) checklist. Data extraction will include generic key information such as the research question and results, the intervention components, and specific epigenetic outcome measures used. Further data regarding the delivery mode of the treatment protocol will be collected. Ethics and dissemination This scoping review will summarize the characteristics of non-pharmaceutical intervention studies on epigenetic aging. This review will be the first step to formally identify key intervention components and delivery modes to guide future research on healthy aging interventions. The results will be disseminated through a peer-reviewed publication and presented at relevant conferences. This review will synthesize information from available publications and does not require further ethical approval. Registration details Open Science Framework https://doi.org/10.17605/OSF.IO/FEHNB.