Eugenol from Syzygium aromaticum enhances longevity and proteostasis in aged yeast

Abstract

Clove (Syzygium aromaticum) extracts promote longevity in several model systems, yet the underlying molecular mechanisms responsible for the pro-longevity remain poorly defined. This study utilized a Saccharomyces cerevisiae model to investigate how clove extracts modulate two primary hallmarks of cellular aging: oxidative damage and the decline of protein quality control systems. Clove extracts promoted increased chronological lifespan (CLS) of yeast cells. The change in longevity was associated with a reduction in both reactive oxygen species (ROS) levels and increased resistance to oxidant and thermal challenges. The appearance of protein aggregates was also limited with treatment with clove extract and is likely linked to induction of the autophagy pathway. Deletion of RAS2 abrogated the enhanced CLS from clove extracts. This observation suggests that the ability of clove extracts to extend the lifespan of S. cerevisiae is dependent on the Ras/PKA (Protein Kinase A) signaling pathway.These results indicate that the enhanced CLS from clove extracts are mediated through improving the maintenance of proteostasis rather than general antioxidant activity. Chemical profiling and comparative bioassays of major constituents identified eugenol as the principal bioactive compound, which successfully replicated the anti-aging and stress-reducing properties of clove extract. Our findings demonstrate that clove extracts, through the bioactive compound eugenol, promote survival in aged cells through reducing oxidative stress and damage and improving the clearance of aggregated proteins to limit proteotoxicity.