scholarly journals RME-1 is required for lifespan extension and increased resistance to stresses associated with decreased insulin/IGF-1-like signaling in Caenorhabditis elegans

2017 ◽  
Vol 69 (3) ◽  
pp. 417-425
Author(s):  
Chul-Kyu Kim ◽  
Sang-Kyu Park
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Growth Factor ◽  
Heat Shock ◽  
Aging Effect ◽  
Lifespan Extension ◽  
Genetic Pathway ◽  
C Elegans ◽  
Age Related ◽  
Underlying Mechanisms

The insulin/insulin-like growth factor (IGF)-1 signaling (IIS) pathway is a conserved life span-modulating genetic pathway. Many genes involved in lifespan extension associated with decreased signaling of the IIS pathway have been identified. In the present study, we found a novel gene required for the effect of the IIS pathway on the stress response and aging in C. elegans. Receptor mediated endocytosis (RME)-1 is expressed ubiquitously and known to be involved in cellular endocytic transport. Knockdown of rme-1abolished the lifespan-extending effect caused by decreased IIS. In addition, resistance to oxidative stress, heat shock and ultraviolet irradiation were significantly decreased when the expression of RME-1 was blocked. The delayed age-related decline in motility observed in age-1 mutants with defects in the IIS pathway was also modulated by RME-1. The expression of sod-3, which is positively correlated with the remaining lifespan of an individual, was decreased by rme-1 knockdown. Our study demonstrates that RME-1 is required for the anti-aging effect associated with decreased IIS. We suggest that endocytic transport could be one underlying mechanisms for longevity via the IIS pathway.

scholarly journals Kynurenine Metabolism Lifespan Extension Mediated by Oxidative Stress Response and Hypoxic Response in C. elegans

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 684-684
Author(s):  
Raul Castro-Portuguez ◽  
Jeremy Meyers ◽  
Sam Freitas ◽  
Hope Dang ◽  
Emily Turner ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Transcription Factors ◽  
Stress Response ◽  
Aging Process ◽  
De Novo ◽  
Kynurenine Pathway ◽  
Oxidative Stress Response ◽  
Lifespan Extension ◽  
Hypoxic Stress ◽  
C Elegans

Abstract Aging is characterized by a progressive decline in the normal physiological functions of an organism, ultimately leading to mortality. Metabolic changes throughout the aging process disrupt the balance and homeostasis of the cell. The kynurenine metabolic pathway is the sole de novo biosynthetic pathway for producing NAD+ from ingested tryptophan. Altered kynurenine pathway activity is associated with both aging and a variety of age-associated diseases, and kynurenine-based interventions can extend lifespan in Caenorhabditis elegans. Our laboratory recently demonstrated knockdown of the kynurenine pathway enzymes kynureninase (KYNU) or 3-hydroxyanthranilic acid dioxygenase (HAAO) increases lifespan by 20-30% in C elegans. However, the mechanism of how these interventions may modulate response against different stressors during the aging process has yet to be explored. Fluorescent reporter strains show the stress-responsive transcription factors skn-1 (ortholog of NRF2/NFE2L2; oxidative stress response) and hif-1 (ortholog of HIF1A; hypoxic stress response) to be highly upregulated when the kynurenine pathway is inhibited. We also demonstrated the increase expression of gst-4 and gcs-1 (transcriptional targets skn-1), which are involved in production of the antioxidant glutathione (GSH), as well as upregulation of cysl-2 (transcriptional target of hif-1), a regulator of cysteine biosynthesis from serine. We hypothesize that lifespan extension resulting from kynurenine pathway inhibition is mediated, at least in part, by upregulation of these transcription factors, providing elevated defense against oxidative stress and hypoxic stress.

scholarly journals Mitochondrial sirtuins sir-2.2 and sir-2.3 regulate lifespan in C. elegans

2017 ◽  
Author(s):  
Sarah M. Chang ◽  
Melanie R. McReynolds ◽  
Wendy Hanna-Rose
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Drug Targets ◽  
Physiological Role ◽  
Oxidative Stress Response ◽  
Altered Expression ◽  
C Elegans ◽  
Mitochondrial Superoxide ◽  
Age Related ◽  
Extended Lifespan

ABSTRACTMitochondrial sirtuins regulate biochemical pathways and are emerging drug targets for metabolic and age-related diseases such as cancer, diabetes, and neurodegeneration. Yet, their functions remain unclear. Here, we uncover a novel physiological role for the C. elegans mitochondrial sirtuins, sir-2.2 and sir-2.3, in lifespan regulation. Using a genetic approach, we demonstrate that sir-2.2 and sir-2.3 mutants live 28-30% longer than controls when fed the normal lab diet of E. coli OP50. Interestingly, this effect is diet specific and is not observed when animals are fed the strain HT115, which is typically used for RNAi experiments. While decreased consumption of food is a known mechanism for lifespan extension, this does not account for the increased lifespan in the mitochondrial sirtuin mutants. sir-2.2 and sir-2.3 mutants display altered expression of genes involved in oxidative stress response, including increased expression of the mitochondrial superoxide dismutase sod-3 and decreased levels of catalases ctl-1 and ctl-2. Like their extended lifespan phenotype, these alterations in oxidative stress gene expression are diet dependent. The mitochondrial sirtuin mutants are more resistant to the lifespan extending effects of low levels of superoxide, suggesting that their increased lifespan involves a hormetic response. Our data suggest that sir-2.2 and sir-2.3 are not completely redundant in function and may possess overlapping yet distinct mechanisms for regulating oxidative stress response and lifespan.

scholarly journals Spatiotemporal regulation of autophagy during Caenorhabditis elegans aging

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Jessica T Chang ◽  
Caroline Kumsta ◽  
Andrew B Hellman ◽  
Linnea M Adams ◽  
Malene Hansen
Keyword(s):  
Caenorhabditis Elegans ◽  
Body Wall ◽  
Lifespan Extension ◽  
Autophagic Flux ◽  
Wild Type ◽  
C Elegans ◽  
Spatiotemporal Regulation ◽  
Age Related ◽  
Autophagic Activity ◽  
Underlying Mechanisms

Autophagy has been linked to longevity in many species, but the underlying mechanisms are unclear. Using a GFP-tagged and a new tandem-tagged Atg8/LGG-1 reporter, we quantified autophagic vesicles and performed autophagic flux assays in multiple tissues of wild-type Caenorhabditis elegans and long-lived daf-2/insulin/IGF-1 and glp-1/Notch mutants throughout adulthood. Our data are consistent with an age-related decline in autophagic activity in the intestine, body-wall muscle, pharynx, and neurons of wild-type animals. In contrast, daf-2 and glp-1 mutants displayed unique age- and tissue-specific changes in autophagic activity, indicating that the two longevity paradigms have distinct effects on autophagy during aging. Although autophagy appeared active in the intestine of both long-lived mutants, inhibition of intestinal autophagy significantly abrogated lifespan extension only in glp-1 mutants. Collectively, our data suggest that autophagic activity normally decreases with age in C. elegans, whereas daf-2 and glp-1 long-lived mutants regulate autophagy in distinct spatiotemporal-specific manners to extend lifespan.

scholarly journals The effect of intrinsic physiological traits on diapause survival and their underlying mechanisms in an annual bee species Bombus impatiens

2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Erin Treanore ◽  
Etya Amsalem
Keyword(s):  
Oxidative Stress ◽  
Life Stage ◽  
Mass Gain ◽  
Nutrient Acquisition ◽  
Bombus Impatiens ◽  
Factors Affecting ◽  
Age Related ◽  
The Face ◽  
Underlying Mechanisms ◽  
Age Range

Abstract In the face of insect declines, identifying phases of the life cycle when insects are particularly vulnerable to mortality is critical to conservation efforts. For numerous annual insect groups, diapause is both a key adaptation that allows survival of inhospitable conditions and a physiologically demanding life stage that can result in high rates of mortality. As bees continue to garner attention as a group experiencing high rates of decline, improving our understanding of how annual bees prepare for diapause and identifying factors that reduce survival is imperative. Here, we studied factors affecting diapause survival length and their underlying mechanisms using an economically and ecologically important annual bee species, Bombus impatiens. We examined how age and mass upon diapause onset correlate with diapause survival length, and the mechanistic role of nutrient acquisition and oxidative stress post pupal eclosion in mediating these effects. Our findings show that both age and mass were strong predictors of diapause survival length. Heavier queens or queens in the age range of ~6–17 days survived longer in diapause. Mass gain was attributed to increases in lipid, protein and glycerol amounts following pupal eclosion, and the ability to deal with oxidative stress was significantly compromised in older pre-diapause queens. Our results demonstrate that age-related shifts in bee physiology and timing of nutrient acquisition may both be critical factors driving diapause survival.

Rubidium chloride increases lifespan through an AMPK/FOXO-dependent pathway in Caenorhabditis elegans

2021 ◽  
Author(s):  
Mengjiao Hao ◽  
Zhikang Zhang ◽  
Yijun Guo ◽  
Huihao Zhou ◽  
Qiong Gu ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Stress Responses ◽  
Aging Effect ◽  
Stress Effect ◽  
Neuroprotective Effects ◽  
C Elegans ◽  
Cycle Arrest ◽  
Age Related ◽  
Promising Target ◽  
Amp Activated Protein Kinase

Abstract AMP-activated protein kinase (AMPK) is involved in life span maintenance, stress responses, and germ cell cycle arrest upon dauer entry. AMPK is currently considered a promising target for preventing age-related diseases. Rubidium is one of the trace elements in human body. As early as the 1970s, RbCl has been was reported to have neuroprotective effects. In this work, we report the anti-aging effect of RbCl in Caenorhabditis elegans. Specifically, we reveal that (1) RbCl does increase the lifespan and enhance stress resistance in C. elegans without disturbing their fecundity. (2) RbCl induces superoxide dismutase (SOD) expression, which is essential for its anti-aging and anti-stress effect. (3) AAK-2 and DAF-16 are essential to the anti-aging efficacy of RbCl, and RbCl can promote DAF-16 translocating into the nucleus, suggesting that RbCl delays aging through regulating AMPK/FOXO pathway. RbCl can be a promising agent against aging related diseases.

scholarly journals Epigallocatechin gallate prevents senescence by alleviating oxidative stress and inflammation in WI-38 human embryonic fibroblasts

RSC Advances ◽  
2019 ◽  
Vol 9 (46) ◽  
pp. 26787-26798 ◽  
Author(s):  
Qiao Zhang ◽  
Yuqing Wu ◽  
Yue Guan ◽  
Fan Ling ◽  
Ying Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Aging Process ◽  
Epigallocatechin Gallate ◽  
Embryonic Fibroblasts ◽  
Age Related ◽  
Underlying Mechanisms ◽  
Human Embryonic Fibroblasts

Increased levels of oxidative stress and inflammation are the underlying mechanisms behind the aging process and age-related diseases.

scholarly journals Fine Particulate Matter Leads to Unfolded Protein Response and Shortened Lifespan by Inducing Oxidative Stress in C. elegans

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Yunli Zhao ◽  
Ling Jin ◽  
Yuxin Chi ◽  
Jing Yang ◽  
Quan Zhen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Particulate Matter ◽  
Fine Particulate Matter ◽  
Metabolic Enzyme ◽  
C Elegans ◽  
Unfolded Protein ◽  
Fine Particulate ◽  
Underlying Mechanisms ◽  
Protein Response ◽  
Phenylbutyric Acid

Oxidative stress has been proven as one of the most critical regulatory mechanisms involved in fine Particulate Matter- (PM2.5-) mediated toxicity. For a better understanding of the underlying mechanisms that enable oxidative stress to participate in PM2.5-induced toxic effects, the current study explored the effects of oxidative stress induced by PM2.5 on UPR and lifespan in C. elegans. The results implicated that PM2.5 exposure induced oxidative stress response, enhanced metabolic enzyme activity, activated UPR, and shortened the lifespan of C. elegans. Antioxidant N-acetylcysteine (NAC) could suppress the UPR through reducing the oxidative stress; both the antioxidant NAC and UPR inhibitor 4-phenylbutyric acid (4-PBA) could rescue the lifespan attenuation caused by PM2.5, indicating that the antioxidant and moderate proteostasis contribute to the homeostasis and adaptation to oxidative stress induced by PM2.5.

scholarly journals A Hot Water Extract of Sideritis scardica Prolongs Life Span and Enhances Heat Shock Resistance in Caenorhabditis elegans

2020 ◽  
Vol 15 (4) ◽  
pp. 1934578X2091728
Author(s):  
Yoshihiko Nishioka ◽  
Seiya Nishikawa ◽  
Toshiyuki Shibata
Keyword(s):  
Heat Stress ◽  
Caenorhabditis Elegans ◽  
Stress Response ◽  
Heat Shock ◽  
Life Span ◽  
Water Extract ◽  
Hot Water ◽  
Control Group ◽  
C Elegans ◽  
Hot Water Extract

Sideritis scardica is a Lamiaceae plant that is endemic to the alpine zone of the Balkan Peninsula. The tea of S. scardica has been handed down as a “tea of longevity” in the Rhodope region of Bulgaria for an unknown amount of time. In this study, we prepared a hot water extract of S. scardica (SHWE) and examined its effects on both life span and stress response in living tissue using Caenorhabditis elegans and its transgenic mutants. The life span of wild-type N2 worms was prolonged by approximately 15% at the SHWE concentration of 5 µg/mL and approximately 22% at the SHWE concentration of 50 µg/mL, as compared with the control group. The effect of SHWE on the expression of heat shock protein 16.2 (HSP-16.2) under heat stress was investigated using TJ375 worms, a transgenic mutant of C. elegans. In the TJ375 worms pretreated with SHWE, the fluorescence intensity of green fluorescent protein fluorescence, which indicates the expression of HSP-16.2, was significantly increased. In the assay using TJ356 worms, the worms pretreated with SHWE did not show the translocation of DAF-16, a forkhead transcription factor class O homolog, from the cytoplasm to nucleus under heat stress. Additionally, under heat stress, the pretreatment of SHWE improved the survival rate of GR1307 worms, a knockout mutant of daf-16. These results indicate that SHWE enhances HSP-16.2 expression through a stress-response pathway (eg, HSF-1 pathway) other than the DAF-16 pathway, resulting in a prolonged life span of C. elegans under heat stress.

scholarly journals Carotenoids: How Effective Are They to Prevent Age-Related Diseases?

Molecules ◽  
2019 ◽  
Vol 24 (9) ◽  
pp. 1801 ◽  
Author(s):  
Bee Ling Tan ◽  
Mohd Esa Norhaizan
Keyword(s):  
Oxidative Stress ◽  
Healthy Aging ◽  
The Elderly ◽  
Antioxidant Systems ◽  
Potential Intervention ◽  
Healthy Longevity ◽  
Age Related ◽  
Underlying Mechanisms ◽  
Endogenous Antioxidant

Despite an increase in life expectancy that indicates positive human development, a new challenge is arising. Aging is positively associated with biological and cognitive degeneration, for instance cognitive decline, psychological impairment, and physical frailty. The elderly population is prone to oxidative stress due to the inefficiency of their endogenous antioxidant systems. As many studies showed an inverse relationship between carotenoids and age-related diseases (ARD) by reducing oxidative stress through interrupting the propagation of free radicals, carotenoid has been foreseen as a potential intervention for age-associated pathologies. Therefore, the role of carotenoids that counteract oxidative stress and promote healthy aging is worthy of further discussion. In this review, we discussed the underlying mechanisms of carotenoids involved in the prevention of ARD. Collectively, understanding the role of carotenoids in ARD would provide insights into a potential intervention that may affect the aging process, and subsequently promote healthy longevity.

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