Evaluation of the Real Effects and Potential Mechanisms of Collagen Peptides in Improving Skin Health During the Senescence Process: Bioinformatics Analysis and A Meta-analysis of Randomized Controlled Trials

• CP significantly increased skin elasticity, hydration, and reduced roughness, with CP complexes enhancing elasticity more. • CP improved skin health in individuals under 48 years but showed reduced benefits with age, particularly for hydration and roughness, while still improving elasticity in those over 48. • Bioinformatics and network pharmacology identified epithelial cells and fibroblasts as key effector cells in skin aging, with accelerated aging genes disrupting their physiological functions through multiple aberrant pathway. • CP could target aging-related genes to reduce oxidative stress, inflammation and apoptosis and provide anti-aging protection. Collagen peptides (CP) are widely recognized as functional foods, yet their effects on skin aging remain debated. This study evaluates the effectiveness of CP supplementation on skin health during aging and investigates how accelerated aging may diminish its benefits. A meta-analysis of 16 randomized controlled trials (CP: 628 participants; control: 607 participants) showed that CP intake significantly increased skin elasticity (SMD = 0.32, P < 0.001), improved hydration (SMD = 0.33, P < 0.05), and reduced roughness (SMD = -0.71, P < 0.001), with CP complexes further enhancing skin elasticity (SMD = 0.70, P < 0.001). The included studies demonstrated low to moderate heterogeneity and good robustness. Subgroup analysis indicated that CP benefits skin elasticity, hydration, and roughness in individuals under 48 years, but its effects decline with age. In individuals over 48 years, CP improved elasticity but had no significant impact on other skin health indicators. Mendelian randomization analysis revealed a significant positive correlation between aging and skin aging biomarkers, suggesting that age-related biological changes accelerate skin aging. Bioinformatics and network pharmacology analyses identified epithelial cells and fibroblasts as key skin effector cells, showing a shift toward epithelial differentiation with aging, which leads to reduced cellular turnover. Accelerated aging genes promote skin aging by disrupting oxidative stress, inflammation, and cell proliferation. Mechanistically, CP was found to target both accelerated aging and anti-aging genes, exerting protective effects by inhibiting oxidative stress, inflammation, and apoptosis. Cross-validation with multiple machine learning models confirmed the reliability of these CP-target interactions. In summary, for individuals within specific age ranges, CP shows promise as a multifunctional bioactive ingredient in nutricosmetics or nutritional interventions, potentially improving skin aging via multiple molecular targets and pathways. A comprehensive study elucidating the effects of CP on skin health and the mechanisms underlying their role in mitigating skin aging. (A) Multi-database search and quantitative analysis of RCTs assessing the impact of CP supplementation on skin health parameters. (B) Subgroup analysis evaluating the influence of age on the effectiveness of CP in enhancing skin health. (C-F) Investigation of the potential mechanisms of CP in combating skin aging through Mendelian randomization, single-cell analysis, and transcriptomic profiling. (G) Cross-validation of the identified skin-aging-related targets of CP using 12 machine learning algorithms to assess their credibility.