Screening and Activity Profiling of Antisenescence Peptides from Silkworm Pupa Protein Hydrolysate: Discovery of a Bioactive Hexapeptide FKVPNM

Aging-associated cognitive decline has prompted interest in naturally derived interventions. This study investigated the antisenescence effects of silkworm pupa protein hydrolysate (SPPH) and its derived hexapeptide, FKVPNM (Ptd5). In d -galactose-induced senescent PC-12 cells, SPPH (1 mg/mL) increased cell viability from 73.5 ± 1.1% (model) to 101.2 ± 0.4% ( p < 0.01) and reduced SA-β-gal-positive cells. Ptd5 significantly downregulated p53, p21, and γ-H2A.X. In vivo, SPPH (200–800 mg/kg) improved spatial memory in d -galactose-aged mice, with the 800 mg/kg group showing increased platform crossings (2.2 ± 0.4 vs 5.8 ± 1.3 in model; p < 0.01) and a longer target quadrant time at 72 h. SPPH also restored hippocampal SIRT1/p53/p21 axis expression. These findings identify FKVPNM as a key bioactive peptide from SPPH with antisenescence activity and suggest SPPH as a candidate dietary intervention for age-related cognitive decline.