Methionine transsulfuration pathway is upregulated in long-lived humans
Abstract
Available evidences point to methionine metabolism as a key target to study the molecular adaptive mechanisms underlying differences in longevity. The plasma methionine metabolic profile was determined using a LC-MS/MS platform to systematically define specific phenotypic patterns associated with genotypes of human extreme longevity (centenarians). Our findings demonstrate the presence of a specific plasma profile associated with human longevity characterized by an enhanced transsulfuration pathway and tricarboxylic acid (TCA) cycle intermediates, as well as a reduced content of specific amino acids. Furthermore, our work reveals that centenarians maintain a strongly correlated methionine metabolism, suggesting an improved network integrity, homeostasis and more tightly regulated metabolism. We have discovered a particular methionine signature related to the condition of extreme longevity, allowing the identification of potential mechanisms and biomarkers of healthy aging.
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Activation of the TSP that generates cysteine and culminates in production of GSH and taurine has previously been associated with pro-longevity interventions.
“Activation of the TSP that generates cysteine and culminates in production of GSH and taurine has previously been associated with pro-longevity interventions.36,70”
From Taurine lowers inflammaging by regulating the NLRP3 inflammasome in macrophages (2026) · cites this paper as [70]
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Genome-wide association study identifies multiple loci influencing human serum metabolite levels
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Mitochondrial Permeability Uncouples Elevated Autophagy and Lifespan Extension
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Metabolic networks of longevity
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One-Carbon Metabolism: Pulling the Strings behind Aging and Neurodegeneration
Lionaki, E., Ploumi, C., & Tavernarakis, N. (2022) · Cells · doi:10.3390/cells11020214 · Cited by 110 · see citing works
Taurine lowers inflammaging by regulating the NLRP3 inflammasome in macrophages
Guan, C., Ryu, S., Dong, M., Zhu, Y., Maeda, R., Youm, Y.-H., Mohanty, S., Kim, H.-H., Orliaguet, L., Dlugos, T., et al. (2026) · Cell · doi:10.1016/j.cell.2026.09.061
- Authors
- Mota-Martorell, N., Jové, M., Borrás, C., Berdún, R., Obis, È., Sol, J., Cabré, R., Pradas, I., Galo-Licona, J. D., Puig, J., Viña, J., & Pamplona, R.
- Affiliations
- Universitat de Lleida (ES)
- Universitat de València (ES)
- Institut d'Investigació Biomèdica de Girona (ES)
- Corresponding author
- Pamplona, Reinald
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2021-01
- Volume
- 162
- Pages
- 38-52
- ISSN
- 0891-5849 (ISSN-L)
- OpenAlex
- W3109540451
- Cited by
- 43
- References
- 3
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 8 · 2023: 13 · 2022: 7 · 2021: 1
- FWCI
- 1.74
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- FP7 Health
- Ministerio de Economía y Competitividad
- Instituto de Salud Carlos III
- Departament d'Innovació, Universitats i Empresa, Generalitat de Catalunya
- Departament de Salut, Generalitat de Catalunya
- Ministerio de Ciencia e Innovación
- Joint Programming Initiative A healthy diet for a healthy life
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Sulfur Compounds in Biology
- Health Sciences › Medicine › Rheumatology › Folate and B Vitamins Research
- Keywords
- methionine metabolism, centenarians, exceptional longevity, plasma metabolome, TCA cycle intermediates, amino acid metabolism
- MeSH terms
- Aged, 80 and over, Chromatography, Liquid, Humans, Longevity, Methionine, Tandem Mass Spectrometry, Metabolome
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