Silkworm-derived hexapeptide FKVPNM reverses d-galactose-induced cellular senescence and cognitive decline

Aging-associated cognitive decline is a growing global health burden, often linked to cellular senescence and neurodegeneration. Current treatments for conditions like Alzheimer's disease and Parkinson's disease offer limited efficacy, driving interest in naturally derived interventions. Bioactive peptides, particularly from dietary sources like silkworm pupa protein hydrolysate (SPPH), show promise in modulating neurological pathways. This study addresses the gap in understanding the specific antisenescence mechanisms and identifying key bioactive components within SPPH that could combat age-related cognitive impairment.

Researchers investigated silkworm pupa protein hydrolysate (SPPH) and its derived hexapeptide, FKVPNM (Ptd5), in both in-vitro and in-vivo models of senescence. For in-vitro studies, d-galactose-induced senescent PC-12 cells were treated with SPPH (1 mg/mL). Key endpoints included cell viability via CCK-8 assay and senescence-associated β-galactosidase (SA-β-gal) staining. In-vivo, d-galactose-aged mice received SPPH (200-800 mg/kg) daily via oral gavage for an unspecified duration. Spatial memory was assessed using the Morris water maze test, and hippocampal expression of senescence markers was analyzed via western blot.

In d-galactose-induced senescent PC-12 cells, SPPH (1 mg/mL) significantly increased cell viability from 73.5 ± 1.1% (model group) to 101.2 ± 0.4% (p < 0.01), indicating a reversal of cellular damage. It also effectively reduced the number of SA-β-gal-positive senescent cells. Further analysis revealed that the hexapeptide FKVPNM (Ptd5) significantly downregulated key senescence markers, including p53, p21, and γ-H2A.X expression. In the in-vivo mouse model, SPPH (800 mg/kg) markedly improved spatial memory in d-galactose-aged mice. The 800 mg/kg group showed a significant increase in platform crossings (5.8 ± 1.3 vs. 2.2 ± 0.4 in the model group; p < 0.01) and spent a longer time in the target quadrant at 72 hours post-training. > SPPH treatment also restored the expression of the hippocampal SIRT1/p53/p21 axis, suggesting a direct modulation of critical aging pathways in the brain. These findings collectively identify FKVPNM as a potent bioactive peptide contributing to SPPH's antisenescence and cognitive-enhancing effects.