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.
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Abbreviations
- AD:
-
Alzheimer’s disease
- Aβ:
-
Amyloid-β
- BCP:
-
β-caryophyllene
- BLAST:
-
Basic local alignment search tool
- CI :
-
Chemotaxis index
- DR:
-
Dietary restriction
- FOXO:
-
Forkhead box protein O
- FUdR:
-
2′-Deoxy-5-fluorouridine
- GFP:
-
Green fluorescent protein
- GRAS:
-
Generally regarded as safe
- H2DCF-DA:
-
7-dichlorodihydrofluoresceindiacetate
- IIS:
-
Insulin/insulin like signaling
- NDs:
-
Neurodegenerative disorders
- NGM:
-
Nematode Growth Medium
- PD:
-
Parkinson’s disease
- ROS:
-
Reactive oxygen species
- TFs:
-
Transcription factors
- YFP:
-
Yellow fluorescent protein
- αS:
-
α-Synuclein
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Acknowledgments
The authors are grateful to the Caenorhabditis elegans Genetics Center (Minneapolis, MN, USA) for providing nematode strains. Authors also heartily acknowledge Director, CSIR-National Botanical Research Institute, Lucknow, Uttar Pradesh, India and Director, National Institute of Technology, Raipur, Chhattisgahr, India for their kind support. Authors also show their sincere gratitude to Ms. Neetu Phulara, Child Development Project Officer, Uttarakhand Govetment, Chakrata, Dehradun, Uttarakhand, India for critically reading the manuscript and providing grammar check.
Funding
SP was financially supported by Indian Council of Medical Research (ICMR), New Delhi, India (Grant Id- 45/11/2018-PHA/BMS/OL) through Senior Research Fellowship grant.
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SCP, SP, and VS conceived, designed, and performed in vivo and in vitro experiments; AJ performed in silico analysis; SCP, SP, and VS analyzed the data; PG and PSC contributed reagents/materials/analysis tools; SCP, SP, and AJ wrote the manuscript. PSC, VS, and PG critically reviewed and edited the manuscript. All authors have critically gone through the manuscript and approved it.
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Phulara, S.C., Pandey, S., Jha, A. et al. Hemiterpene compound, 3,3-dimethylallyl alcohol promotes longevity and neuroprotection in Caenorhabditis elegans. GeroScience 43, 791–807 (2021). https://doi.org/10.1007/s11357-020-00241-w
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DOI: https://doi.org/10.1007/s11357-020-00241-w