학술논문

Oligosaccharides from agar extends lifespan through activation of unfolded protein response via SIR-2.1 in Caenorhabditis elegans.
Document Type
Article
Source
European Journal of Nutrition. Dec2022, Vol. 61 Issue 8, p4179-4190. 12p. 2 Charts, 7 Graphs.
Subject
*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
Language
ISSN
1436-6207
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. [ABSTRACT FROM AUTHOR]