Upcycled porcine whole-blood protein hydrolysate attenuates age-related sarcopenia-like phenotypes in Caenorhabditis elegans in an RSKS-1-dependent manner.

Abstract

Sarcopenia is an age-associated loss of muscle mass and function that increases the risk of frailty, disability, and mortality, yet there are no FDA-approved agents specifically indicated for sarcopenia. Porcine whole-blood protein hydrolysate (PWBPH), an upcycled protein resource from slaughter by-products, has been proposed to support muscle-related outcomes, but whether it mitigates functional deterioration during physiological aging and which regulatory programs are required remain unclear. PWBPH was enriched in essential amino acids and comprised low-molecular-weight peptides (<1 kDa). Here, we evaluated PWBPH in Caenorhabditis elegans as an in vivo model of muscle aging. Chronic exposure to a low dose of PWBPH (0.01%, w/v) from early adulthood attenuated age-dependent functional decline, as assessed by pharyngeal pumping, swimming performance, and locomotor activity. PWBPH mitigated age-associated myosin loss and preserved mitochondrial network integrity. Consistently, PWBPH maintained ATP content and mitochondrial DNA copy number (a proxy for mitochondrial content), and blunted the age-induced upregulation of mitochondrial stress-response transcripts. PWBPH also improved locomotor resistance to acute oxidative challenge (H2O2). Notably, these benefits were abolished in rsks-1 mutants, the C. elegans ortholog of ribosomal protein S6 kinase (S6K), indicating that RSKS-1/S6K is genetically required for PWBPH-mediated protection. Collectively, our findings show that PWBPH delays sarcopenia-like phenotypes in aging C. elegans, associated with preserved mitochondrial status and stress resilience, and support further evaluation of PWBPH as a food-derived, upcycled peptide ingredient for muscle health span.