4.4 Article

Hemiterpene compound, 3,3-dimethylallyl alcohol promotes longevity and neuroprotection inCaenorhabditis elegans

Journal

GEROSCIENCE
Volume 43, Issue 2, Pages 791-807

Publisher

SPRINGER
DOI: 10.1007/s11357-020-00241-w

Keywords

Prenol; Antiaging; C; elegans; Reactive oxygen species; Neuroprotection

Funding

  1. Indian Council ofMedical Research (ICMR), NewDelhi, India [Id45/11/2018-PHA/BMS/OL]

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The study demonstrated that Prenol could significantly extend the lifespan of C. elegans and alleviate protein aggregation. By activating specific genes and transcription factors, Prenol improved stress tolerance and health-span of the worms. These findings suggest that small molecules like Prenol could be explored as potential therapeutics against aging and age-related conditions.
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 modelCaenorhabditis 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-beta induced paralysis and reduced alpha-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 inC. 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.

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