Production and Optimization of Anti-Aging Peptides from Pleurotus eryngii Mushroom Feet: Mechanistic Insights via Integrated Transcriptomics and Metabolomics

This study established an optimized process for obtaining anti-aging peptides from <i>Pleurotus eryngii</i> mushroom feet (PEMFPeps). Using response surface methodology, high yields of protein (51.31 ± 3.00%) and peptides (48.71 ± 0.17% hydrolysis degree) were achieved. In a D-galactose-induced PC12 cell aging model, the simulated digests (SID-PEMFPeps) exhibited potent anti-aging effects at a concentration of 1 mg/mL. An integrated transcriptomic and metabolomic approach was employed to systematically investigate the underlying mechanisms. The results revealed that Integrated transcriptomic and metabolomic analyses showed that SID-PEMFPeps alleviated cellular senescence through multi-dimensional regulation of transcriptional and metabolic networks. This included modulating key pathways related to oxidative stress, synaptic function, and energy metabolism (e.g., glutamatergic synapse, pentose phosphate pathway, and TCA cycle), and reversing the aberrant expression of aging-associated genes (e.g., <i>Arap3, Grin2d and Npy1r</i>). Our findings demonstrate that SID-PEMFPeps are promising candidates for functional foods targeting age-related dysfunction though their efficacy and safety in vivo require further validation.