Abstract
Terpenes and their derivatives have been used conventionally as potential dietary supplements to boost the nutritional value of endless food products. Several plant-based complex terpenoid and their derivatives have been reported for a wide range of medicinal and nutritional properties. However, their simple counterparts, whose production is relatively easy, sustainable, and economic from food-grade microbial sources, have not been studied yet for any such biological activities. The present study aimed to investigate the longevity-promoting property and neuromodulatory effects of 3,3-dimethylallyl alcohol (Prenol), one of the simplest forms of terpenoid and a constituent of fruit aroma, in the animal model Caenorhabditis elegans. Prenol supplementation (0.25 mM) augmented the lifespan of wild-type nematodes by 22.8% over the non-treated worms. Moreover, a suspended amyloid-β induced paralysis and reduced α-synuclein aggregation were observed in Prenol-treated worms. The lifespan extending properties of Prenol were correlated with ameliorated physiological parameters and increased stress (heat and oxidative) tolerance in C. elegans. In silico and gene-specific mutant studies showed that pro-longevity transcription factors DAF-16, HSF-1, and SKN-1 were involved in the improved lifespan and health-span of Prenol-treated worms. Transgenic green fluorescent protein-reporter gene expression analysis and relative mRNA quantification (using real-time PCR) demonstrated an increase in the expression of DAF-16, HSF-1, and SKN-1 transcription factors and their downstream target genes in Prenol-treated worms. Together, the findings suggest that small molecules, like Prenol, could be explored as a potential alternate to develop therapeutics against aging and age-related ailments.