ArticleScience advances2025
Dietary methionine restriction started late in life promotes healthy aging in a sex-specific manner.
Registry-linked trialAbstract read
In one paragraph
Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04701346 (Dietary Sulfur Amino Acid Restriction, Energy Metabolism and Obesity), which is not on this map. Cited by 8 papers.
0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–field-weighted citation impact
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Dietary Sulfur Amino Acid Restriction, Energy Metabolism and Obesity
Who cites it
8 citing papers in PubMed.
- Live-cell DNMT3A "catalysome" mapping using engineered methyl-transfer pathways.Nucleic acids research · 2026Article
- The hallmarks of protein and amino acid restriction in aging and longevity.Cell press blue · 2026Article
- Methionine-supplemented longevity diet increases growth hormone, GLP-1, and FGF21; reduces frailty; and promotes healthspan.Cell metabolism · 2026Article
- Methionine restriction and mimetics to ameliorate human aging and disease.Trends in endocrinology and metabolism: TEM · 2026Review
- Metabolic Crosstalk Between Host and Tumor as a Circuit of Resilience in Cancer Therapy.Cells · 2026Review
- Nutritional methionine restriction modulates gut microbiota and propionate/GPR41 signaling to mitigate diabetic kidney disease.NPJ science of food · 2026Article
- Anti-aging and Anti-inflammatory Dietary Interventions in Multiple Sclerosis: A Narrative Review.Neurology and therapy · 2026Review
- Dietary methionine mitigates immune-mediated damage by enhancing renal clearance of cytokines.Cell metabolism · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
44 authors.
Ulalume Hernández-ArcigaAging Institute of UPMC and the University of Pittsburgh, Pittsburgh, PA, USA.ORCID 0000-0003-4995-7172
Ceda StamenkovicDevelopment, Aging, and Regeneration Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.ORCID 0009-0000-4442-0144
Shweta YadavAging Institute of UPMC and the University of Pittsburgh, Pittsburgh, PA, USA.ORCID 0000-0001-9760-3382
Chiara NicolettiDevelopment, Aging, and Regeneration Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.ORCID 0000-0002-0872-6506
Wafaa N AlbalawyRenal Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID 0009-0000-9279-2671
Farazdaq Al HammoodAging Institute of UPMC and the University of Pittsburgh, Pittsburgh, PA, USA.
Tiffany Fuentes GonzalezAging Institute of UPMC and the University of Pittsburgh, Pittsburgh, PA, USA.ORCID 0009-0009-5737-4090
Maitreyi U NaikwadiAging Institute of UPMC and the University of Pittsburgh, Pittsburgh, PA, USA.
Aidan GrahamAging Institute of UPMC and the University of Pittsburgh, Pittsburgh, PA, USA.
Christian SmarzAging Institute of UPMC and the University of Pittsburgh, Pittsburgh, PA, USA.
Gabriela J LittleAging Institute of UPMC and the University of Pittsburgh, Pittsburgh, PA, USA.
Sean-Paul G WilliamsAging Institute of UPMC and the University of Pittsburgh, Pittsburgh, PA, USA.
Brenda McMahonVascular Medicine Institute, Department of Medicine, University of Pittsburgh, PA, USA.
Ian J SipulaCenter for Metabolism and Mitochondrial Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Amber M VandevenderCenter for Metabolism and Mitochondrial Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.ORCID 0000-0002-3719-0747
Byron ChuanPulmonary, Allergy, Critical Care, and Sleep Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Diana CookeOrentreich Foundation for the Advancement of Science Inc., Cold Spring, NY, USA.
Antonio F M PintoMass Spectrometry Core for Proteomics and Metabolomics, Salk Institute for Biological Studies, La Jolla, CA, USA.ORCID 0000-0002-1573-8011
Lisa C FloresBarshop Institute for Longevity and Aging Studies, San Antonio, TX, USA.
Hannah L HartmanRenal Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID 0000-0002-9347-4621
Jolene K DiedrichMass Spectrometry Core for Proteomics and Metabolomics, Salk Institute for Biological Studies, La Jolla, CA, USA.ORCID 0000-0001-6489-4558
Robert T BrookeEpigenetic Clock Development Foundation, Torrance, CA, USA.ORCID 0000-0001-8492-5198
Jonathan K AlderPulmonary, Allergy, Critical Care, and Sleep Medicine, University of Pittsburgh, Pittsburgh, PA, USA.ORCID 0000-0003-3741-6512
Krystle A FrahmDepartment of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID 0000-0002-9269-4294
Laura E PascalDepartment of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID 0000-0003-3840-1662
Emma StoltDepartment of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.ORCID 0000-0002-4481-225X
Hannibal TroensegaardDepartment of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
Bente ØvrebøDepartment of Food Safety, Norwegian Institute of Public Health, Oslo, Norway.ORCID 0000-0002-2928-4575
Amany ElshorbagyDepartment of Physiology, Faculty of Medicine, University of Alexandria, Alexandria, Egypt.ORCID 0000-0002-8624-860X
Elsa MolinaNext Generation Sequencing Core, Salk Institute for Biological Studies, La Jolla, CA, USA.ORCID 0000-0003-1603-5438
Kathrine J VinknesDepartment of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
Roderick J TanRenal Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID 0000-0003-1012-1722
Ora A WeiszRenal Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Marta BuenoPulmonary, Allergy, Critical Care, and Sleep Medicine, University of Pittsburgh, Pittsburgh, PA, USA.ORCID 0000-0001-7140-9899
Oliver EickelbergPulmonary, Allergy, Critical Care, and Sleep Medicine, University of Pittsburgh, Pittsburgh, PA, USA.ORCID 0000-0001-7170-0360
Matthew L SteinhauserAging Institute of UPMC and the University of Pittsburgh, Pittsburgh, PA, USA.
Toren FinkelAging Institute of UPMC and the University of Pittsburgh, Pittsburgh, PA, USA.ORCID 0000-0002-0726-3546
Gene P AblesOrentreich Foundation for the Advancement of Science Inc., Cold Spring, NY, USA.ORCID 0000-0002-8238-0726
Yuji IkenoBarshop Institute for Longevity and Aging Studies, San Antonio, TX, USA.
Thomas OlsenDepartment of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.ORCID 0000-0003-1805-5221
Alessandra SaccoDevelopment, Aging, and Regeneration Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.ORCID 0000-0003-1669-0221
Michael J JurczakCenter for Metabolism and Mitochondrial Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Stacey J Sukoff RizzoAging Institute of UPMC and the University of Pittsburgh, Pittsburgh, PA, USA.ORCID 0000-0002-1460-8127
Andrey A ParkhitkoAging Institute of UPMC and the University of Pittsburgh, Pittsburgh, PA, USA.ORCID 0000-0001-9852-8329
Funding
The IU/JAX Alzheimer's Disease Precision Models Center: Rat F344U54AG054345 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI Gregory W Carter · 2016 to 2026
$95.6MTRANSGENIC COREP30AG013319 · NIA · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI JAMES FLOYD NELSON · 1995 to 2026
$30.6MVARIABILITY, STABILITY & SMOOTHNESS OF WALKINGP30AG024827 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI JENNIFER S BRACH · 2004 to 2026
$28.6MTriState SenNET (Lung and Heart) Tissue Map and Atlas consortiumU54AG075931 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI TOREN FINKEL, Melanie Koenigshoff · 2021 to 2026
$14.0MSan Diego Nathan Shock CenterP30AG068635 · NIA · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI SHADEL, GERALD · 2020 to 2024
$6.0MResource Development CoreU54DK137329 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Gerard L Apodaca · 2023 to 2026
$4.8MMechanisms of Telomere-Mediated Lung DiseaseR01HL135062 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Jonathan K. Alder · 2018 to 2026
$4.1MEffect of Renal Nerves on Chronic Kidney DiseaseR01DK131991 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Roderick Jason Tan · 2022 to 2026
$2.6MDeciphering the crosstalk between methionine metabolism and methyltransferases in health and diseaseR35GM146869 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Andrey A Parkhitko · 2022 to 2026
$2.3MReduced thioredoxin in both the cytosol and mitochondria: a key modulator of age-related cancer development in Trx1KO x Trx2KO mice?R01AG070034 · NIA · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI IKENO, YUJI · 2021 to 2025
$2.0MMetabolomics clocks as a tool to explore mechanisms of agingR01AG082696 · NIA · TUFTS UNIVERSITY BOSTON · PI Daniel Edward Promislow · 2024 to 2026
$1.9MMethionine Cycle as a Mechanistic Hub for the Hallmarks of AgingR01AG082801 · NIA · BROWN UNIVERSITY · PI Andrey A Parkhitko, MARC TATAR · 2023 to 2026
$1.7MBLRD VA I01 BX005680NHLBI NIH HHS R01 HL135062NIA NIH HHS P30 AG013319NIA NIH HHS P30 AG024827NIA NIH HHS P30 AG068635NIA NIH HHS R00 AG057792NIA NIH HHS R01 AG070034NIA NIH HHS R01 AG082696NIA NIH HHS R01 AG082801NIA NIH HHS R03 AG075651NIA NIH HHS U54 AG054345NIA NIH HHS U54 AG075931NIDDK NIH HHS K01 DK115543NIDDK NIH HHS R01 DK131991NIDDK NIH HHS R01 DK138967NIDDK NIH HHS R21 DK121266NIDDK NIH HHS U54 DK137329NIGMS NIH HHS R35 GM146869NIH HHS S10 OD023684
Abstract
Aging is associated with dysregulated methionine metabolism and increased levels of enzymes in the tyrosine degradation pathway (TDP). To investigate the efficacy of targeting either methionine metabolism or the TDP for healthspan improvement in advanced age, we initiated dietary MetR or TDP inhibition in 18-month-old C57BL/6J mice. MetR significantly improved neuromuscular function, metabolic health, lung function, and frailty. In addition, we confirmed improved neuromuscular function from dietary MetR in 5XFAD mice, whose weight was not affected by MetR. We did not observe benefits with TDP inhibition. Single-nucleus RNA and ATAC sequencing of muscle revealed cell type-specific responses to MetR, although MetR did not significantly affect mouse aging epigenetic clock markers. Similarly, an 8-week MetR intervention in a human trial (NCT04701346) showed no significant impact on epigenetic clocks. The observed benefits from late-life MetR provide translational rationale to develop MetR mimetics as an antiaging intervention.
Indexed as
AgingHealthy AgingMethionineAgedAnimalsDietEpigenesis, GeneticFemaleHumansMaleMiceMice, Inbred C57BLSex FactorsTyrosineMethionineTyrosine
Identifiers
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LicenceCC BY-NC
Read underepoch 390
Registered trials
NCT04701346ClinicalTrials.gov
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.