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

Rasulova, Madina; Zecic, Alexandra; Moreno, José Manuel Monje; Vandemeulebroucke, Lieselot; Dhondt, Ineke; Braeckman, Bart P.

doi:10.3390/metabo11020105

Cited by 14 publications

(23 citation statements)

References 62 publications

(114 reference statements)

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“…The IIS mutant daf-2, bearing a mutation in the insulin/IGF-1 receptor, is characterized by living about twice as long as the wild type and having about five-fold higher trehalose levels compared with the wild type [ 125 ]. Since trehalose function is not only circumscribed as a reserve carbohydrate but also as an important stress-protecting molecule in different organisms, Honda et al analyzed the effect of adding trehalose to the culture medium of C. elegans and found that 5 mM of trehalose extended the lifespan and thermotolerance and retarded aging independently of age state, apparently since trehalose prevents the formation of protein aggregates that normally accumulate with age [ 126 ].…”

Section: Impacts Of Carbohydrate Metabolism On Lifespanmentioning

confidence: 99%

Effects of High Dietary Carbohydrate and Lipid Intake on the Lifespan of C. elegans

Franco-Juárez

Gómez-Manzo

Hernández-Ochoa

et al. 2021

Cells

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Health and lifespan are influenced by dietary nutrients, whose balance is dependent on the supply or demand of each organism. Many studies have shown that an increased carbohydrate–lipid intake plays a critical role in metabolic dysregulation, which impacts longevity. Caenorhabditis elegans has been successfully used as an in vivo model to study the effects of several factors, such as genetic, environmental, diet, and lifestyle factors, on the molecular mechanisms that have been linked to healthspan, lifespan, and the aging process. There is evidence showing the causative effects of high glucose on lifespan in different diabetic models; however, the precise biological mechanisms affected by dietary nutrients, specifically carbohydrates and lipids, as well as their links with lifespan and longevity, remain unknown. Here, we provide an overview of the deleterious effects caused by high-carbohydrate and high-lipid diets, as well as the molecular signals that affect the lifespan of C. elegans; thus, understanding the detailed molecular mechanisms of high-glucose- and lipid-induced changes in whole organisms would allow the targeting of key regulatory factors to ameliorate metabolic disorders and age-related diseases.

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Section: Impacts Of Carbohydrate Metabolism On Lifespanmentioning

confidence: 99%

Effects of High Dietary Carbohydrate and Lipid Intake on the Lifespan of C. elegans

Franco-Juárez

Gómez-Manzo

Hernández-Ochoa

et al. 2021

Cells

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“…In C. elegans , endogenous glucose is stored in the form of trehalose, a non-reducing disaccharide, or glycogen, a branched polysaccharide [ 97 ]. Trehalose presumably acts as a stress protectant against multiple stresses [ 104 , 105 , 106 , 107 , 108 , 109 ] and as a longevity assurance sugar in C. elegans [ 107 , 110 , 111 ]. Although not to the same extent as daf-2 mutants, PHB depletion causes the accumulation of large amounts of trehalose.…”

Section: Phb Has a Broad Impact On The C Elegans Metabolomementioning

confidence: 99%

“…Moreover, trehalose supplementation from the YA stage significantly extends lifespan [ 107 ]. However, the requirement of trehalose for daf-2 longevity has been recently brought into question, because a deficiency in trehalose synthesis mildly shortened daf-2 lifespan [ 109 ], compared with previous studies [ 107 , 111 ]. Similar to trehalose supplementation, exogenous addition of lactate, which induces mitohormesis, leads to stress resistance and survival [ 112 ].…”

Section: Phb Has a Broad Impact On The C Elegans Metabolomementioning

confidence: 99%

The Mitochondrial Prohibitin (PHB) Complex in C. elegans Metabolism and Ageing Regulation

Lourenço

Artal‐Sanz

2021

Metabolites

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The mitochondrial prohibitin (PHB) complex, composed of PHB-1 and PHB-2, is an evolutionarily conserved context-dependent modulator of longevity. This extremely intriguing phenotype has been linked to alterations in mitochondrial function and lipid metabolism. The true biochemical function of the mitochondrial PHB complex remains elusive, but it has been shown to affect membrane lipid composition. Recent work, using large-scale biochemical approaches, has highlighted a broad effect of PHB on the C. elegans metabolic network. Collectively, the biochemical data support the notion that PHB modulates, at least partially, worm longevity through the moderation of fat utilisation and energy production via the mitochondrial respiratory chain. Herein, we review, in a systematic manner, recent biochemical insights into the impact of PHB on the C. elegans metabolome.

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“…Other processes occur in dauer larvae to maintain enzyme activity at higher temperatures. For example, in wild-type and daf-2 worms, the presence of exogenous or endogenously produced trehalose increased the thermotolerance of the worms (105,106). Trehalose has also been found to increase the thermal stability of enzymes in vitro (107).…”

Section: Mdh-1 and Mdh-2 Functions In C Elegans Dauer Larvaementioning

confidence: 99%

Kinetic characterization and thermostability ofC. eleganscytoplasmic and mitochondrial malate dehydrogenases

Thomas

Cassidy

Robinson

et al. 2021

Preprint

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Malate dehydrogenase (MDH) catalyzes the conversion of NAD+ and malate to NADH and oxaloacetate in the last step of the citric acid cycle. Eukaryotes have at least two MDH isozymes, one that is imported into the mitochondria and one that remains in the cytoplasm. We overexpressed and purified Caenorhabditis elegans cytoplasmic MDH-1 (F46E10.10) and mitochondrial MDH-2 (F20H11.3) in E. coli. Our goal was to compare the kinetic and structural properties of these enzymes because C. elegans can survive adverse environmental conditions, such as lack of food and elevated temperatures. In steady-state enzyme kinetics assays, we determined that the KM values for oxaloacetate were 54 and 52 μM, and the KM values for NADH were 61 and 107 μM, for MDH-1 and MDH-2, respectively. We partially purified endogenous MDH from a mixed population of worms and separated MDH-1 from MDH-2 using anion exchange chromatography. Both endogenous enzymes had a KM for oxaloacetate similar to that of the corresponding recombinant enzyme. The reaction velocities of the recombinant enzymes had slightly different temperature-dependencies: MDH-1 and MDH-2 had maximum activity at 40 °C and 35 °C, respectively. In a thermotolerance assay, MDH-1 was much more thermostable than MDH-2. Molecular homology modeling predicted that MDH-1 had more salt-bridges between the subunits than mammalian MDH1 enzymes, and these ionic interactions may contribute to its thermostability. In contrast, the MDH-2 homology model predicted fewer ionic interaction between the subunits compared to mammalian MDH2 enzymes. These results suggest that the increased structural stability of MDH-1 may facilitate its ability to remain active in adverse environmental conditions. In contrast, MDH-2 may use other strategies, such as protein binding partners, to function under similar conditions.

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

Cited by 14 publications

References 62 publications

Effects of High Dietary Carbohydrate and Lipid Intake on the Lifespan of C. elegans

Effects of High Dietary Carbohydrate and Lipid Intake on the Lifespan of C. elegans

The Mitochondrial Prohibitin (PHB) Complex in C. elegans Metabolism and Ageing Regulation

Kinetic characterization and thermostability ofC. eleganscytoplasmic and mitochondrial malate dehydrogenases

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