scholarly journals Elevated Trehalose Levels in C. elegans daf-2 Mutants Increase Stress Resistance, Not Lifespan

Metabolites ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 105
Author(s):  
Madina Rasulova ◽  
Aleksandra Zečić ◽  
Jose Manuel Monje Moreno ◽  
Lieselot Vandemeulebroucke ◽  
Ineke Dhondt ◽  
...  
Keyword(s):  
Growth Factor ◽  
Stress Resistance ◽  
Lifespan Extension ◽  
Insulin Like Growth Factor ◽  
Carbohydrate Accumulation ◽  
C Elegans ◽  
Metabolic Signature ◽  
Trehalose Accumulation

The C. elegans insulin/IGF-1 (insulin-like growth factor 1) signaling mutant daf-2 recapitulates the dauer metabolic signature—a shift towards lipid and carbohydrate accumulation—which may be linked to its longevity and stress resistance phenotypes. Trehalose, a disaccharide of glucose, is highly upregulated in daf‑2 mutants and it has been linked to proteome stabilization and protection against heat, cold, desiccation, and hypoxia. Earlier studies suggested that elevated trehalose levels can explain up to 43% of the lifespan extension observed in daf-2 mutants. Here we demonstrate that trehalose accumulation is responsible for increased osmotolerance, and to some degree thermotolerance, rather than longevity in daf-2 mutants. This indicates that particular stress resistance phenotypes can be uncoupled from longevity.

scholarly journals Antiaging Effects of Vicatia thibetica de Boiss Root Extract on Caenorhabditis elegans and Doxorubicin-Induced Premature Aging in Adult Mice

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Wenwen Liu ◽  
Yunhui Guan ◽  
Sicong Qiao ◽  
Jiqun Wang ◽  
Keting Bao ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Stress Resistance ◽  
Chinese Herb ◽  
Premature Aging ◽  
Lifespan Extension ◽  
Root Extract ◽  
Antioxidant Ability ◽  
C Elegans ◽  
Adult Mice ◽  
Heat Stress Resistance

The roots of Vicatia thibetica de Boiss are a kind of Chinese herb with homology of medicine and food. This is the first report showing the property of the extract of Vicatia thibetica de Boiss roots (HLB01) to extend the lifespan as well as promote the healthy parameters in Caenorhabditis elegans (C. elegans). For doxorubicin- (Doxo-) induced premature aging in adult mice, HLB01 counteracted the senescence-associated biomarkers, including P21 and γH2AX. Interestingly, HLB01 promoted the expression of collagen in C. elegans and mammalian cell systemically, which might be one of the essential factors to exert the antiaging effects. In addition, HLB01 was also found as a scavenger of free radicals, thereby performing the antioxidant ability. Lifespan extension by HLB01 was also dependent on DAF-16 and HSF-1 via oxidative stress resistance and heat stress resistance. Taken together, overall data suggested that HLB01 could extend the lifespan and healthspan of C. elegans and resist Doxo-induced senescence in mice via promoting the expression of collagen, antioxidant potential, and stress resistance.

Lifespan extension by reduction of the growth hormone‐insulin‐like growth factor‐1 axis: relation to caloric restriction

2003 ◽  
Vol 17 (9) ◽  
pp. 1108-1109 ◽  
Author(s):  
Isao Shimokawa ◽  
Yoshikazu Higami ◽  
Tomoshi Tsuchiya ◽  
Hiroshi Otani ◽  
Toshimitsu Komatsu ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Caloric Restriction ◽  
Lifespan Extension ◽  
Insulin Like Growth Factor

scholarly journals Deleting IGF-1 receptor from forebrain neurons confers neuroprotection during stroke and upregulates endocrine somatotropin

2016 ◽  
Vol 37 (2) ◽  
pp. 396-412 ◽  
Author(s):  
C Daniel De Magalhaes Filho ◽  
Laurent Kappeler ◽  
Joëlle Dupont ◽  
Julien Solinc ◽  
Sonia Villapol ◽  
...  
Keyword(s):  
Growth Factor ◽  
Stress Resistance ◽  
Hippocampal Neurons ◽  
Growth Factor Receptor ◽  
Growth Factor Signaling ◽  
Insulin Like Growth Factor ◽  
Age Related ◽  
Therapeutic Concepts ◽  
Forebrain Neurons ◽  
The Brain

Insulin-like growth factors control numerous processes, namely somatic growth, metabolism and stress resistance, connecting this pathway to aging and age-related diseases. Insulin-like growth factor signaling also impacts on neurogenesis, neuronal survival and structural plasticity. Recent reports demonstrated that diminished insulin-like growth factor signaling confers increased stress resistance in brain and other tissues. To better understand the role of neuronal insulin-like growth factor signaling in neuroprotection, we inactivated insulin-like growth factor type-1-receptor in forebrain neurons using conditional Cre-LoxP-mediated gene targeting. We found that brain structure and function, including memory performance, were preserved in insulin-like growth factor receptor mutants, and that certain characteristics improved, notably synaptic transmission in hippocampal neurons. To reveal stress-related roles of insulin-like growth factor signaling, we challenged the brain using a stroke-like insult. Importantly, when charged with hypoxia-ischemia, mutant brains were broadly protected from cell damage, neuroinflammation and cerebral edema. We also found that in mice with insulin-like growth factor receptor knockout specifically in forebrain neurons, a substantial systemic upregulation of growth hormone and insulin-like growth factor-I occurred, which was associated with significant somatic overgrowth. Collectively, we found strong evidence that blocking neuronal insulin-like growth factor signaling increases peripheral somatotropic tone and simultaneously protects the brain against hypoxic–ischemic injury, findings that may contribute to developing new therapeutic concepts preventing the disabling consequences of stroke.

scholarly journals Crotamiton derivative JM03 extends lifespan and improves oxidative and hypertonic stress resistance in Caenorhabditis elegans via inhibiting OSM-9

2021 ◽  
Author(s):  
Keting Bao ◽  
Jiali Feng ◽  
Wenwen Liu ◽  
Zhifan Mao ◽  
Tianyue Sun ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Animal Model ◽  
Caenorhabditis Elegans ◽  
Stress Resistance ◽  
Lifespan Extension ◽  
Aging Effects ◽  
Hypertonic Stress ◽  
C Elegans ◽  
Promising Application ◽  
Application Prospects

While screening our in-house 1,072 marketed drugs for their ability to extend the lifespan using Caenorhabditis elegans (C. elegans) as an animal model, crotamiton (N-ethyl-o-crotonotoluidide) showed anti-aging activity and was selected for further structural optimization. After replacing the ortho-methyl of crotamiton with ortho-fluoro, crotamiton derivative JM03 was obtained and showed better activity in terms of lifespan-extension and stress resistance than crotamiton. It was further explored that JM03 extended the lifespan of C. elegans through osmotic avoidance abnormal-9 (OSM-9). Besides, JM03 improves the ability of nematode to resist oxidative stress and hypertonic stress through OSM-9, but not osm-9/capsaicin receptor related-2 (OCR-2). Then the inhibition of OSM-9 by JM03 reduces the aggregation of Q35 in C. elegans via upregulating the genes associated with proteostasis. SKN-1 signaling was also found to be activated after JM03 treatment, which might contribute to proteostasis, stress resistance and lifespan extension. In summary, this study explored a new small molecule derived from crotamiton, which has efficient anti-oxidative, anti-hypertonic and anti-aging effects, and could further lead to promising application prospects.

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.

Stress resistance and lifespan extension of Caenorhabditis elegans enhanced by peptides from mussel (Mytilus edulis) protein hydrolyzate

2018 ◽  
Vol 9 (6) ◽  
pp. 3313-3320 ◽  
Author(s):  
Yue Zhou ◽  
Qinggang Xu ◽  
Xinghua Zhou ◽  
Shuang Song ◽  
Beiwei Zhu
Keyword(s):  
Caenorhabditis Elegans ◽  
Mrna Expression ◽  
Mytilus Edulis ◽  
Stress Resistance ◽  
Lifespan Extension ◽  
Protein Hydrolyzate ◽  
Lipofuscin Accumulation ◽  
C Elegans

Mussel (Mytilus edulis) peptides increased stress resistance and reduced endogenous ROS level and lipofuscin accumulation of C. elegans. Mussel peptides could contribute to healthspan extension of C. elegans through regulating the mRNA expression of daf-2 and daf-16.

scholarly journals Role of insulin/insulin-like growth factor-1 signaling pathway genes on the lifespan of Caenorhabditis elegans

2020 ◽  
Vol 11 (2) ◽  
Author(s):  
Siti Bazilah Zulkefli ◽  
Ahmad Nazrun Shuid ◽  
Goon Jo Aan
Keyword(s):  
Caenorhabditis Elegans ◽  
Growth Factor ◽  
Signaling Pathway ◽  
Model Organism ◽  
Insulin Like Growth Factor ◽  
C Elegans ◽  
Expression Of Genes ◽  
Differential Expression Of Genes

Aging process is influenced by the insulin/insulin-like growth factor-1 signaling (IIS) pathway or IGF-1 signaling pathway. Studies done on the genes of this pathway were found to affect longevity. However, no conclusive results have been drawn.The purpose of this systematic review is to summarize the function of genes involved in the IIS pathway of Caenorhabditis Elegans (C. elegans), a nematode commonly used as a model organism in molecular genetics and developmental biology. A literature search for relevant studies was done through PubMed and Scopus databases using MeSH keywords Caenorhabditis elegans, C. elegans, nematode, genes, RNA, DNA, IIS pathway, IGF pathway, lifespan, and longevity. The search was limited to studies that were published in the last ten years (2008-May 2018). After exclusion of duplicates, review papers, human, in vitro, and other organismal studies, a total of 76 research articles were selected for further assessments. Data relevant to the effects of IIS genes on the lifespan ofC. eleganswas independently extracted. Reduction of daf-2 and age-1 and overexpression of sir-2.1 were reported to promote increment of the lifespan of C. elegans.  Furthermore, differentially expressed genes that were involved in the protection against oxidative stress, pathogen attack, and toxicity includeins-18, numr-1/-2, sgk-1, and rgs-1. The knockdown of daf-2, age-1, and overexpression of sir-2.1 genes prolonged the lifespan of C. elegans while knockdown of daf-16, hsf-1, sir-2.1 as well as skn-1 shorten the lifespan of C. elegans.In conclusion, the differential expression of genes in the IIS pathway prolongs the lifespan of C. elegans.

scholarly journals ATF-4 and hydrogen sulfide signalling mediate longevity from inhibition of translation or mTORC1

2020 ◽  
Author(s):  
Cyril Statzer ◽  
Richard Venz ◽  
Monet Bland ◽  
Stacey Robida-Stubbs ◽  
Jin Meng ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Protein Synthesis ◽  
Hydrogen Sulfide ◽  
Stress Response ◽  
Stress Resistance ◽  
Lifespan Extension ◽  
C Elegans ◽  
Mechanistic Target Of Rapamycin ◽  
Therapeutic Benefits ◽  
Transcription Program

AbstractInhibition of mTORC1 (mechanistic target of rapamycin 1) slows ageing, but mTORC1 supports fundamental processes that include protein synthesis, making it critical to elucidate how mTORC1 inhibition increases lifespan. Under stress conditions, the integrated stress response (ISR) globally suppresses protein synthesis, resulting in preferential translation of the transcription factor ATF-4. Here we show in C. elegans that the ATF-4 transcription program promotes longevity and that ATF-4 upregulation mediates lifespan extension from mTORC1 inhibition. ATF-4 activates canonical anti-ageing mechanisms but also increases expression of transsulfuration enzymes to promote hydrogen sulfide (H2S) production. ATF-4-induced H2S production mediates longevity and stress resistance from C. elegans mTORC1 suppression, and ATF4 drives H2S production in mammalian dietary restriction. This H2S boost increases protein persulfidation, a protective modification of redox-reactive cysteines. Increasing H2S levels, or enhancing mechanisms that H2S modulates through persulfidation, may represent promising strategies for mobilising therapeutic benefits of the ISR or mTORC1 inhibition.

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