Unveiling the Epigenetic Impact of Vegan vs. Omnivorous Diets on Aging: Insights from the Twins Nutrition Study (TwiNS)

Geroscience has emerged as a field focusing on interventions to attenuate molecular changes associated with aging. While lifestyle modifications, medications, and social factors are recognized influencers of the aging process, a comprehensive understanding of the intricate molecular mechanisms necessitates an in-depth exploration of the epigenetic landscape. Notably, the specific epigenetic clock and predictor effects of a vegan diet, compared to an omnivorous counterpart, remain inadequately explored, despite indications of potential impacts on aging-related outcomes. This study addresses this knowledge gap by examining the impact of an eight-week entirely plant-based or healthy omnivorous diet on blood DNA methylation in paired twins. Results show distinct responses, with the vegan cohort solely exhibiting significant decreases in overall epigenetic age acceleration (PC GrimAge, PC PhenoAge, DunedinPACE), including among specific systems (Inflammation, Heart, Hormone, Liver, and Metabolic), aligning with anti-aging effects of plant-based diets. Analyses of methylation surrogates of clinical, metabolite, and protein markers indicate diet-specific shifts, while exemplifying DNA methylation markers in predicting complex traits influenced by diet. Comprehensive epigenome-wide analysis unveils diet-specific differentially methylated loci, offering insights into influenced pathways. This study sheds light on the advantageous aging benefits of a healthy vegan diet, while providing a foundation for future personalized interventions using epigenetic age clocks in promoting overall well-being. ### Competing Interest Statement Dr. Dwaraka, Dr. Carreras-Gallo, Aaron Lin, Logan Turner, Dr. Mendez, Hannah Went, and Ryan Smith are all employees of TruDiagnostic Inc. Dr Gardner reported receiving funding from Beyond Meat outside the submitted work. Dr J. L. Sonnenburg is a Chan Zuckerberg Biohub investigator. No other disclosures were reported. ### Clinical Trial NCT05297825 ### Funding Statement The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study followed the ethical standards of the Declaration of Helsinki and was approved by the Stanford University Human Subjects Committee on March 9, 2022. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the presesnt study are available upon reasonable request to the corresponding authors.