NFYB-1 regulates mitochondrial function and longevity via lysosomal prosaposin

Tharyan, Rebecca George; Annibal, Andrea; Schiffer, Isabelle; Laboy, Raymond; Atanassov, Ilian; Weber, Anna Luise; Gerisch, Birgit; Antebi, Adam

doi:10.1038/s42255-020-0200-2

Cited by 37 publications

(29 citation statements)

References 58 publications

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“…Life span analysis. Life span analyses were performed at 20°C as previously reported 78,79 . Data were plotted to calculate mean, median, and maximum lifespans using Microsoft Excel 16.12 and GraphPad Prism 7 Software.…”

Section: Methodsmentioning

confidence: 99%

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Regulation of the one carbon folate cycle as a shared metabolic signature of longevity

et al. 2021

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The metabolome represents a complex network of biological events that reflects the physiologic state of the organism in health and disease. Additionally, specific metabolites and metabolic signaling pathways have been shown to modulate animal ageing, but whether there are convergent mechanisms uniting these processes remains elusive. Here, we used high resolution mass spectrometry to obtain the metabolomic profiles of canonical longevity pathways in C. elegans to identify metabolites regulating life span. By leveraging the metabolomic profiles across pathways, we found that one carbon metabolism and the folate cycle are pervasively regulated in common. We observed similar changes in long-lived mouse models of reduced insulin/IGF signaling. Genetic manipulation of pathway enzymes and supplementation with one carbon metabolites in C. elegans reveal that regulation of the folate cycle represents a shared causal mechanism of longevity and proteoprotection. Such interventions impact the methionine cycle, and reveal methionine restriction as an underlying mechanism. This comparative approach reveals key metabolic nodes to enhance healthy ageing.

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Section: Methodsmentioning

confidence: 99%

“…Worm RNAi was conducted as described previously 78 , 79 . Briefly, WT wild‐type worms were fed with HT115 (DE3) bacteria transformed with L4440 vector that expresses a double‐stranded RNA against the targeted gene.…”

Section: Methodsmentioning

confidence: 99%

Regulation of the one carbon folate cycle as a shared metabolic signature of longevity

et al. 2021

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“…Nevertheless, our finding is promising in view of the reported role of lysosomes in regulating lifespan in a cross-talk with mitochondrial function (Liu et al, 2020;Ramachandran et al, 2019;Tharyan et al, 2020).…”

Section: F I G U R Ementioning

confidence: 76%

Prohibitin depletion extends lifespan of a TORC2/SGK‐1 mutant through autophagy and the mitochondrial UPR

et al. 2021

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Mitochondrial function, nutrient signalling and autophagy regulate ageing across phyla. However, their exact mechanisms and interactions in lifespan modulation still remain elusive. The mitochondrial prohibitin (PHB) complex is a strongly evolutionarily conserved ring-like macromolecular structure (Artal-Sanz & Tavernarakis, 2009a), important for mitochondrial morphogenesis and membrane maintenance with a poorly understood biochemical function . PHB depletion severely perturbs mitochondrial homeostasis causing an induction of the mitochondrial unfolded protein response, UPR mt (Hernando-Rodriguez

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“…All strains were grown and maintained on NGM agar seeded with E. coli (OP50) at 20°C except for the glp-1(e2141)ts strain, which underwent a thermal shift to 25°C leading to germline loss. Standard procedures for culturing and maintaining strains were used 59 . Complete strain list is provided in the Supplementary Table 3.…”

Section: Methodsmentioning

confidence: 99%

Regulation of the one carbon folate cycle as a shared metabolic signature of longevity

Annibal

Tharyan

Schonewolff

et al. 2020

Preprint

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AbstractThe metabolome represents a complex network of biological events that reflects the physiologic state of the organism in heath and disease. Additionally, specific metabolites and metabolic signaling pathways have been shown to modulate animal ageing, but whether there are convergent mechanisms uniting these processes remains elusive. Here, we used high resolution mass spectrometry to obtain the metabolomic profiles of canonical longevity pathways in C. elegans and identify metabolites regulating life span. By leveraging the metabolomic profiles across pathways, we found that one carbon metabolism and the folate cycle were pervasively regulated in common. We observed similar changes in long lived mouse models of reduced insulin/IGF signaling. Genetic manipulation of pathway enzymes and supplementation with one carbon metabolites reveal that regulation of the folate cycle represents a shared causal mechanism of longevity and proteoprotection.

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NFYB-1 regulates mitochondrial function and longevity via lysosomal prosaposin

Cited by 37 publications

References 58 publications

Regulation of the one carbon folate cycle as a shared metabolic signature of longevity

Regulation of the one carbon folate cycle as a shared metabolic signature of longevity

Prohibitin depletion extends lifespan of a TORC2/SGK‐1 mutant through autophagy and the mitochondrial UPR

Regulation of the one carbon folate cycle as a shared metabolic signature of longevity

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