Study Identifies Hydroxyproline and Branched-Chain Amino Acid Synergy in Extending C. elegans Lifespan

A preclinical study shows that combining hydroxyproline with branched-chain amino acids enhances lifespan and healthspan-related phenotypes in Caenorhabditis elegans, accompanied by metabolic and microbial remodeling.

Researchers found that combinations of collagen-associated hydroxyproline (Hyp) and branched-chain amino acids (BCAAs) improved lifespan- and healthspan-related phenotypes in C. elegans in a BCAA- and dose-dependent manner.

The strongest combined treatments enhanced resistance to thermal and oxidative stress, preserved age-associated motility and muscle structure, and increased ATP-related readouts.

Multi-omics profiling demonstrated that these effects were accompanied by distinct microbiota signatures, altered NAD precursor-related metabolites including nicotinic acid ribonucleoside (NaR), and transcriptional enrichment in energy metabolism, proteostasis, and extracellular-matrix remodeling.

The combination of Hyp and BCAAs addresses both structural (extracellular-matrix) and metabolic (energy metabolism, proteostasis) pathways, suggesting a multi-layered approach to addressing age-related decline.

The positive correlation identified between Rhodococcus abundance and NaR levels provides a candidate pathway for microbiome-mediated NAD precursor regulation.

The findings may inform the development of longevity-focused nutritional formulations, although clinical utility remains unproven as the study was limited to nematode models under specific culture conditions.

This early-stage research highlights growing scientific interest in the interaction between specific amino acid profiles, the gut microbiome, and cellular energetics.

Whether the synergistic effects of hydroxyproline and branched-chain amino acids on lifespan, muscle integrity, and NAD precursor levels can be replicated in mammalian models.