α- and β-Santalols Delay Aging in via Preventing Oxidative Stress and Protein Aggregation.

α- and β-Santalol (santalol isomers) are the most abundant sesquiterpenoids found in sandalwood, contributing to its pleasant fragrance and wide-spectrum bioactivity. This study aimed at identifying the antiaging and antiaggregation mechanism of α- and β-santalol using the genetic tractability of an model . The results showed that santalol isomers retard aging, improved health span, and inhibited the aggregation of toxic amyloid-β (Aβ) and polyglutamine repeats (Q35, Q40, and HtnQ150) in models for Alzheimer's and Huntington's disease, respectively. The genetic study, reporter gene expression, RNA-based reverse genetic approach (RNA interferences/RNAi), and gene expression analysis revealed that santalol isomers selectively regulate SKN-1/Nrf2 and EOR-1/PLZF transcription factors through the RTK/Ras/MAPK-dependent signaling axis that could trigger the expression of several antioxidants and protein aggregation inhibitory genes, ., 4, 1, 10, 1, 4, and 5, which extend longevity and help minimize age-induced protein oxidation and aggregation. We believe that these findings will further promote α- and β-santalol to become next-generation prolongevity and antiaggregation molecules for longer and healthier life.