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- Title
Oligosaccharides from agar extends lifespan through activation of unfolded protein response via SIR-2.1 in Caenorhabditis elegans.
- Authors
Desaka, Natsumi; Nishikawa, Hitomi; Honda, Yuji; Matsumoto, Kenji; Matsuzaki, Chiaki; Mizushima, Katsura; Takagi, Tomohisa; Naito, Yuji; Higashimura, Yasuki
- Abstract
Purpose: Agaro-oligosaccharides (AGO), hydrolysis products of agarose, is known to have antioxidant and anti-inflammatory properties. Speculating that AGO is effective for preventing aging, we investigated the longevity-supporting effects of AGO and their mechanisms using Caenorhabditis elegans. Methods: Caenorhabditis elegans were fed AGO from young adulthood. The lifespan, locomotory activity, lipofuscin accumulation, and heat stress resistance of the worms were examined. To elucidate mechanisms of AGO-mediated longevity, we conducted comprehensive expression analysis using microarrays. Moreover, we used quantitative real-time PCR (qRT-PCR) to verify the genes showing differential expression levels. Furthermore, we measured the lifespan of loss-of-function mutants to determine the genes related to AGO-mediated longevity. Results: AGO extended the lifespan of C. elegans, reduced lipofuscin accumulation, and maintained vigorous locomotion. The microarray analysis revealed that the endoplasmic reticulum-unfolded protein response (ER-UPR) and insulin/insulin-like growth factor-1-mediated signaling (IIS) pathway were activated in AGO-fed worms. The qRT-PCR analysis showed that AGO treatment suppressed sir-2.1 expression, which is a negative regulator of ER-UPR. In loss-of-function mutant of sir-2.1, AGO-induced longevity and heat stress resistance were decreased or cancelled completely. Furthermore, the pro-longevity effect of AGO was decreased in loss-of-function mutants of abnormal Dauer formation (daf) -2 and daf-16, which are IIS pathway-related genes. Conclusion: AGO delays the C. elegans aging process and extends their lifespan through the activations of ER-UPR and the IIS pathway.
- Subjects
OLIGOSACCHARIDE analysis; POLYSACCHARIDES; CONNECTIVE tissue growth factor; CAENORHABDITIS elegans; CULTURE media (Biology); ANIMAL experimentation; ENDOPLASMIC reticulum; MICROARRAY technology; HYDROLASES; HELMINTHS; T-test (Statistics); GENE expression; CELLULAR signal transduction; OLIGOSACCHARIDES; KAPLAN-Meier estimator; DESCRIPTIVE statistics; LONGEVITY; POLYMERASE chain reaction; DATA analysis software
- Publication
European Journal of Nutrition, 2022, Vol 61, Issue 8, p4179
- ISSN
1436-6207
- Publication type
Article
- DOI
10.1007/s00394-022-02957-1