Astragaloside IV Extends Lifespan of Caenorhabditis elegans by Improving Age-Related Functional Declines and Triggering Antioxidant Responses

AbstractAging and fertility are two interconnected processes. From invertebrates to mammals, absence of the germline increases longevity. Here we show that loss of function of sul-2, the Caenorhabditis elegans steroid sulfatase (STS), raises the pool of sulfated steroid hormones, increases longevity and ameliorates protein aggregation diseases. This increased longevity requires factors involved in germline-mediated longevity (daf-16, daf-12, kri-1, tcer-1 and daf-36 genes) although sul-2 mutations do not affect fertility. Interestingly, sul-2 is only expressed in sensory neurons, suggesting a regulation of sulfated hormones state by environmental cues. Treatment with the specific STS inhibitor STX64, as well as with testosterone-derived sulfated hormones reproduces the longevity phenotype of sul-2 mutants. Remarkably, those treatments ameliorate protein aggregation diseases in C. elegans, and STX64 also Alzheimer’s disease in a mammalian model. These results open the possibility of reallocating steroid sulfatase inhibitors or derivates for the treatment of aging and aging related diseases.

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Random forest classification for predicting lifespan-extending chemical compounds

Scientific Reports ◽

10.1038/s41598-021-93070-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Sofia Kapsiani ◽

Brendan J. Howlin

Keyword(s):

Caenorhabditis Elegans ◽

Random Forest ◽

Molecular Descriptors ◽

Area Under The Curve ◽

Chemical Compounds ◽

Research Area ◽

Importance Measure ◽

Random Forest Algorithm ◽

Molecular Fingerprints ◽

Age Related

AbstractAgeing is a major risk factor for many conditions including cancer, cardiovascular and neurodegenerative diseases. Pharmaceutical interventions that slow down ageing and delay the onset of age-related diseases are a growing research area. The aim of this study was to build a machine learning model based on the data of the DrugAge database to predict whether a chemical compound will extend the lifespan of Caenorhabditis elegans. Five predictive models were built using the random forest algorithm with molecular fingerprints and/or molecular descriptors as features. The best performing classifier, built using molecular descriptors, achieved an area under the curve score (AUC) of 0.815 for classifying the compounds in the test set. The features of the model were ranked using the Gini importance measure of the random forest algorithm. The top 30 features included descriptors related to atom and bond counts, topological and partial charge properties. The model was applied to predict the class of compounds in an external database, consisting of 1738 small-molecules. The chemical compounds of the screening database with a predictive probability of ≥ 0.80 for increasing the lifespan of Caenorhabditis elegans were broadly separated into (1) flavonoids, (2) fatty acids and conjugates, and (3) organooxygen compounds.

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Early-life chronic di(2-ethylhexyl)phthalate exposure worsens age-related long-term associative memory decline associated with insulin/IGF-1 signaling and CRH-1/CREB in Caenorhabditis elegans

Journal of Hazardous Materials ◽

10.1016/j.jhazmat.2021.126044 ◽

2021 ◽

pp. 126044

Author(s):

Chun Ming How ◽

Ting-An Lin ◽

Vivian Hsiu-Chuan Liao

Keyword(s):

Caenorhabditis Elegans ◽

Associative Memory ◽

Early Life ◽

Memory Decline ◽

Phthalate Exposure ◽

Age Related ◽

Ethylhexyl Phthalate

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Guarana (Paullinia cupana) Extract Protects Caenorhabditis elegans Models for Alzheimer Disease and Huntington Disease through Activation of Antioxidant and Protein Degradation Pathways

Oxidative Medicine and Cellular Longevity ◽

10.1155/2018/9241308 ◽

2018 ◽

Vol 2018 ◽

pp. 1-16 ◽

Cited By ~ 15

Author(s):

Patrícia Ferreira Boasquívis ◽

Giovanna Melo Martins Silva ◽

Franciny Aparecida Paiva ◽

Rodrigo Marinho Cavalcanti ◽

Cecília Verônica Nunez ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Protein Misfolding ◽

Therapeutic Potential ◽

High Energy ◽

Protective Effects ◽

Independent Manner ◽

Paullinia Cupana ◽

Age Related ◽

Polyq Protein ◽

Underlying Mechanisms

Guarana (Paullinia cupana) is largely consumed in Brazil in high energy drinks and dietary supplements because of its stimulant activity on the central nervous system. Although previous studies have indicated that guarana has some protective effects in Parkinson’s (PD), Alzheimer’s (AD), and Huntington’s (HD) disease models, the underlying mechanisms are unknown. Here, we investigated the protective effects of guarana hydroalcoholic extract (GHE) in Caenorhabditis elegans models of HD and AD. GHE reduced polyglutamine (polyQ) protein aggregation in the muscle and also reduced polyQ-mediated neuronal death in ASH sensory neurons and delayed β-amyloid-induced paralysis in a caffeine-independent manner. Moreover, GHE’s protective effects were not mediated by caloric restriction, antimicrobial effects, or development and reproduction impairment. Inactivation of the transcription factors SKN-1 and DAF-16 by RNAi partially blocked the protective effects of GHE treatment in the AD model. We show that the protective effect of GHE is associated with antioxidant activity and modulation of proteostasis, since it increased the lifespan and proteasome activity, reduced intracellular ROS and the accumulation of autophagosomes, and increased the expression of SOD-3 and HSP-16.2. Our findings suggest that GHE has therapeutic potential in combating age-related diseases associated with protein misfolding and accumulation.

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Ferrous-glutathione coupling mediates ferroptosis and frailty in Caenorhabditis elegans

10.1101/594408 ◽

2019 ◽

Cited By ~ 1

Author(s):

Nicole L. Jenkins ◽

Simon A. James ◽

Agus Salim ◽

Fransisca Sumardy ◽

Terence P. Speed ◽

...

Keyword(s):

Cell Death ◽

Caenorhabditis Elegans ◽

Ferrous Iron ◽

Somatic Tissue ◽

Glutathione Depletion ◽

Death Process ◽

C Elegans ◽

Regulated Cell Death ◽

Age Related ◽

Ageing Rate

All eukaryotes require iron. Replication, detoxification, and a cancer-protective form of regulated cell death termed ferroptosis1, all depend on iron metabolism. Ferrous iron accumulates over adult lifetime in the Caenorhabditis elegans model of ageing2. Here we show that glutathione depletion is coupled to ferrous iron elevation in these animals, and that both occur in late life to prime cells for ferroptosis. We demonstrate that blocking ferroptosis, either by inhibition of lipid peroxidation or by limiting iron retention, mitigates age-related cell death and markedly increases lifespan and healthspan in C. elegans. Temporal scaling of lifespan is not evident when ferroptosis is inhibited, consistent with this cell death process acting at specific life phases to induce organismal frailty, rather than contributing to a constant ageing rate. Because excess age-related iron elevation in somatic tissue, particularly in brain3–5, is thought to contribute to degenerative disease6, 7, our data indicate that post-developmental interventions to limit ferroptosis may promote healthy ageing.

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

The Journals of Gerontology Series A ◽

10.1093/gerona/glab329 ◽

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.

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Secoisolariciresinol Diglucoside Delays the Progression of Aging-Related Diseases and Extends the Lifespan of Caenorhabditis elegans via DAF-16 and HSF-1

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/1293935 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13

Author(s):

Min Lu ◽

Lin Tan ◽

Xiao-Gang Zhou ◽

Zhong-Lin Yang ◽

Qing Zhu ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Body Movement ◽

Mrna Level ◽

Secoisolariciresinol Diglucoside ◽

Neuroprotective Effects ◽

Sesame Seeds ◽

C Elegans ◽

Age Related ◽

6 Hydroxydopamine ◽

And Oxidative Stress

Secoisolariciresinol diglucoside (SDG) is a phytoestrogen and rich in food flaxseed, sunflower seeds, and sesame seeds. Among the beneficial pharmacological activities of SDG on health, many are age related, such as anticancer, antidiabetes, antioxidant, and neuroprotective effects. Thus, we investigated if SDG had an effect on antiaging in Caenorhabditis elegans (C. elegans). Our results showed that SDG could extend the lifespan of C. elegans by up to 22.0%, delay age-related decline of body movement, reduce the lethality of heat and oxidative stress, alleviate dopamine neurodegeneration induced by 6-hydroxydopamine (6-OHDA), and decrease the toxicity of Aβ protein in C. elegans. SDG could increase the expression of the downstream genes of DAF-16, DAF-12, NHR-80, and HSF-1 at mRNA level. SDG could not extend the lifespan of mutants from genes daf-16, hsf-1, nhr-80, daf-12, glp-1, eat-2, and aak-2. The above results suggested that SDG might enhance the stress resistance, delay the progression of aging-related diseases, and extend the lifespan of C. elegans via DAF-16 and HSF-1.

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