A comparative study of the effects of high protein diets of soy and dairy on healthy aging by integrating multi-omics approaches

The global aging population necessitates optimal dietary protein strategies to mitigate age-related decline. However, few studies have linked soy and dairy protein intake to aging. This study investigated soy and dairy protein impacts on aging through epidemiological and animal analysis. Epidemiological data linked higher soy (not dairy) protein intake with slower biological aging. In animal experiments, the effects of 15 % and 30 % (protein energy supply ratios) casein diet (CPD) and soy protein diet (SPD) on aging-related health outcomes, aging phenotypes and its molecular mechanisms in middle-aged rats were explored. After 27 weeks feeding, compared to 15 % SPD, 30 % SPD significantly reduced adiposity, improved lipid profiles, enhanced memory and muscle performance, while 30 % CPD failed to demonstrate comparable improvements. Also, 30 % SPD alleviated liver and kidney impairment, decreased aging markers (p53, p16, p21) levels and SASP factors. Mechanically, 30 % SPD suppressed mTORC1 activation via decreased serum branched-chain amino acids. Furthermore, gut microbiota analysis revealed that SPD reshaped gut microbiota composition, enriched beneficial taxa such as Akkermansia and Duncaniella, and decreased pathogenic bacteria Fusobacterium, compared with CPD. Metabolomics further found that SPD specifically reduced phospholipid metabolites such as LPC 22:4-SN1, O-phosphatecholine, which were strongly correlated with behavioral index and SASP factors. Integrative analysis identified significant associations between SPD-enriched microbiota (Prevotellaceae_UCG-001 and Defluviitaleaceae_UCG-011) and metabolites and aging phenotypes. Collectively, soy protein exerts superior anti-aging effects over casein through coordinated suppression of mTORC1 driven senescence and modulation of gut microbiota-metabolite. This study provides a basis for prioritizing soy protein in healthy aging dietary strategies.