Methionine transsulfuration pathway is upregulated in long-lived humans

Mota‐Martorell, Natàlia; Jové, Mariona; Borrás, Consuelo; Berdún, Rebeca; Òbis, Èlia; Sol, Joaquím; Cabré, Rosanna; Pradas, Irene; Galo-Licona, José Daniel; Puig, Josep; Viña, José; Pamplona, Reinald

doi:10.1016/j.freeradbiomed.2020.11.026

Cited by 28 publications

(29 citation statements)

References 99 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The copyright holder for this preprint this version posted February 28, 2022. ; https://doi.org/10.1101/2022.02.28.481982 doi: bioRxiv preprint Significantly, virtually all aspects of the DC profile increase with chronological age and age-related disease (Auro et al, 2014;Cheng et al, 2015;Marron et al, 2019;Menni et al, 2013;Mota-Martorell et al, 2021;Yeri et al, 2019). High isocitrate, aconitate and malate are associated with frailty, cardiovascular disease and mortality in humans (Cheng et al, 2015;Marron et al, 2019;Yeri et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Telomerase deficiency in humans is associated with systemic age-related changes in energy metabolism

James

Sagi‐Kiss

Bennett

et al. 2022

Preprint

View full text Add to dashboard Cite

SUMMARYUnderlying mechanisms of plasma metabolite signatures of human ageing and age-related diseases are not clear but telomere attrition and dysfunction are central to both. Dyskeratosis Congenita (DC) is associated with mutations in the telomerase enzyme complex (TERT, TERC, DKC1) and progressive telomere attrition. We show extracellular citrate is repressed by canonical telomerase function in vitro and associated with DC leukocyte telomere attrition in vivo; leading to the hypothesis that altered citrate metabolism detects telomere dysfunction. However, citrate and senescence factors only weakly distinguished DC patients from controls, whereas other tricarboxylic acid cycle metabolites, lactate and especially pyruvate distinguished them with high significance, consistent with further metabolism of citrate and lactate in the liver and kidneys. Citrate uptake in certain organs modulates age-related disease in mice and our data has similarities with age-related disease signatures in humans. Our results have implications for the early diagnosis of telomere dysfunction and anti-senescence therapeutics.HighlightsExtracellular citrate is regulated by telomere function in vitro and in vivo.Dyskeratosis Congenita (DC) is a human disease characterized by systemic telomere attrition, which showed an age-related plasma energetic profile, distinct from age-related disease and that of centenarians.The DC profile strikingly out-performed senescence factors in discriminating DC from controls, and pyruvate associated with a low lactate:pyruvate ratio is potentially a useful and cheap minimally invasive diagnostic aid for DC and telomere dysfunction.Mechanistically DC systemic metabolism is indicative of a shift to reduced pyruvate dehydrogenase activity, glycolysis and/or increased citrate and lactate production followed by further metabolism in the kidneys and liver.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Lactate and pyruvate levels are also associated with chronological ageing in humans (Auro et al, 2014; Menni et al, 2013; Mota-Martorell et al, 2021). Lactate and pyruvate metabolism takes place predominantly in the liver and kidneys (Jang et al, 2019) and increased plasma pyruvate was the most consistent change we observed in DC patients.…”

Section: Discussionmentioning

confidence: 99%

Telomerase deficiency in humans is associated with systemic age-related changes in energy metabolism

James

Sagi‐Kiss

Bennett

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Moreover, cbs-1 overexpression in the nematode intestine or body wall muscles extends lifespan at standard (20 °C) and high (25 °C) rearing temperatures [ 137 ]. A recent study reported a unique plasma metabolic profile of centenarians characterized by increased transsulfuration pathway intermediates such as Hcy, cystathionine, and taurine [ 138 ]. When cysteine is used instead of serine, the products of CBS catalysis are cystathionine and H 2 S. There is increasing evidence for the role of H 2 S on aging regulation, although its effects on different species are contradictory [ 60 , 139 , 140 ].…”

Section: One-carbon Metabolism In Agingmentioning

confidence: 99%

One-Carbon Metabolism: Pulling the Strings behind Aging and Neurodegeneration

Lionaki

Ploumi

Tavernarakis

2022

Cells

View full text Add to dashboard Cite

One-carbon metabolism (OCM) is a network of biochemical reactions delivering one-carbon units to various biosynthetic pathways. The folate cycle and methionine cycle are the two key modules of this network that regulate purine and thymidine synthesis, amino acid homeostasis, and epigenetic mechanisms. Intersection with the transsulfuration pathway supports glutathione production and regulation of the cellular redox state. Dietary intake of micronutrients, such as folates and amino acids, directly contributes to OCM, thereby adapting the cellular metabolic state to environmental inputs. The contribution of OCM to cellular proliferation during development and in adult proliferative tissues is well established. Nevertheless, accumulating evidence reveals the pivotal role of OCM in cellular homeostasis of non-proliferative tissues and in coordination of signaling cascades that regulate energy homeostasis and longevity. In this review, we summarize the current knowledge on OCM and related pathways and discuss how this metabolic network may impact longevity and neurodegeneration across species.

show abstract

“…It is worth noticing that methionine is one of the amino acids essential for human life, frequently found in food containing large proteins [ 12 ]. Methionine is involved in many important biochemical processes such as methionine cycle, trans-sulphuration pathway and polyamine biosynthesis [ 13 ]. In the course of the metabolic pathways, it undergoes many chemical transformations [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

“…Methionine is involved in many important biochemical processes such as methionine cycle, trans-sulphuration pathway and polyamine biosynthesis [ 13 ]. In the course of the metabolic pathways, it undergoes many chemical transformations [ 13 ]. Considering its applications for medical purposes, it is important to study its interactions with metal cations, in particular its effect on the reduction of various substances [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Electroreduction of Bi(III) Ions at a Cyclically Renewable Liquid Silver Amalgam Film Electrode in the Presence of Methionine

et al. 2021

View full text Add to dashboard Cite

The catalytic influence of methionine (Mt) on the electroreduction of Bi(III) ions on the novel, cyclically renewable liquid silver amalgam film electrode (R–AgLAFE) in a non-complexing electrolyte solution was examined. The presence of methionine leads to a multistep reaction mechanism, where the transfer of the first electron is the rate limiting step, which is the subject of catalytic augmentation. The catalytic activity of methionine is a consequence of its ability to remove water molecules from the bismuth ion coordination sphere, as well as to form active complexes on the electrode surface, facilitating the electron transfer process.

show abstract

Methionine transsulfuration pathway is upregulated in long-lived humans

Cited by 28 publications

References 99 publications

Telomerase deficiency in humans is associated with systemic age-related changes in energy metabolism

Telomerase deficiency in humans is associated with systemic age-related changes in energy metabolism

One-Carbon Metabolism: Pulling the Strings behind Aging and Neurodegeneration

Electroreduction of Bi(III) Ions at a Cyclically Renewable Liquid Silver Amalgam Film Electrode in the Presence of Methionine

Contact Info

Product

Resources

About