ArticleNature communications2024
Protein restriction slows the development and progression of pathology in a mouse model of Alzheimer's disease.
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Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17citing papers in PubMed
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Who cites it
17 citing papers in PubMed.
- The hallmarks of protein and amino acid restriction in aging and longevity.Cell press blue · 2026Article
- Lifelong restriction of dietary valine has sex-specific benefits for health and lifespan in mice.Nature aging · 2026Article
- Bench to bedside: is rapamycin headed for the docTOR?GeroScience · 2026Review
- Restriction of Individual Branched-Chain Amino Acids has Distinct Effects on the Development and Progression of Alzheimer's Disease in 3xTg Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Sleeve gastrectomy improves metabolic health, cognition, and Alzheimer's Disease pathology in 3xTG mice.bioRxiv : the preprint server for biology · 2026Article
- Mechanistic advances in exercise‑mediated regulation of autophagy dysfunction in Alzheimer's disease (Review).International journal of molecular medicine · 2026Review
- FGF21 signals through hindbrain neurons to alter food intake and energy expenditure during dietary protein restriction.Cell reports · 2026Article
- Lifelong restriction of dietary valine has sex-specific benefits for health and lifespan in mice.bioRxiv : the preprint server for biology · 2025Article
- Fasting is required for many of the benefits of calorie restriction in the 3xTg mouse model of Alzheimer's disease.Nature communications · 2025Article
- Article
- Accumulation of Damaging Lipids in the Arf1-Ablated Neurons Promotes Neurodegeneration through Releasing mtDNA and Activating Inflammatory Pathways in Microglia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Acarbose ameliorates Western diet-induced metabolic and cognitive impairments in the 3xTg mouse model of Alzheimer's disease.GeroScience · 2025Article
- mTORC1, the maestro of cell metabolism and growth.Genes & development · 2025Review
- Late-life protein or isoleucine restriction impacts physiological and molecular signatures of aging.Nature aging · 2024Article
- Caveolae with GLP-1 and NMDA Receptors as Crossfire Points for the Innovative Treatment of Cognitive Dysfunction Associated with Neurodegenerative Diseases.Molecules (Basel, Switzerland) · 2024Review
- Late-life isoleucine restriction promotes physiological and molecular signatures of healthy aging.bioRxiv : the preprint server for biology · 2024Article
- Caveolae with serotonin and NMDA receptors as promising targets for the treatment of Alzheimer's disease.International journal of physiology, pathophysiology and pharmacology · 2024Review
Corrections and comments
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Authors and funding
22 authors.
Reji BabygirijaDepartment of Medicine, University of Wisconsin-Madison, Madison, WI, USA.
Michelle M SonsallaDepartment of Medicine, University of Wisconsin-Madison, Madison, WI, USA.ORCID http://orcid.org/0000-0001-8493-1416
Jericha MillDepartment of Biochemistry, University of Wisconsin-Madison, Madison, WI, 53706, USA.
Isabella JamesDepartment of Biochemistry, University of Wisconsin-Madison, Madison, WI, 53706, USA.
Jessica H HanCellular and Molecular Biology Graduate Program, University of Wisconsin-Madison, Madison, WI, USA.
Cara L GreenDepartment of Medicine, University of Wisconsin-Madison, Madison, WI, USA.ORCID http://orcid.org/0000-0002-2293-9364
Mariah F CalubagDepartment of Medicine, University of Wisconsin-Madison, Madison, WI, USA.
Gina WadeDepartment of Biochemistry, University of Wisconsin-Madison, Madison, WI, 53706, USA.
Anna TobonDepartment of Medicine, University of Wisconsin-Madison, Madison, WI, USA.
John MichaelDepartment of Medicine, University of Wisconsin-Madison, Madison, WI, USA.
Michaela M TrautmanDepartment of Medicine, University of Wisconsin-Madison, Madison, WI, USA.
Ryan MatoskaDepartment of Medicine, University of Wisconsin-Madison, Madison, WI, USA.
Chung-Yang YehDepartment of Medicine, University of Wisconsin-Madison, Madison, WI, USA.
Isaac GrunowDepartment of Medicine, University of Wisconsin-Madison, Madison, WI, USA.
Heidi H PakDepartment of Medicine, University of Wisconsin-Madison, Madison, WI, USA.ORCID http://orcid.org/0000-0002-3287-6133
Michael J RigbyWaisman Center, University of Wisconsin-Madison, Madison, WI, 53705, USA.ORCID http://orcid.org/0000-0001-8809-2648
Dominique A BaldwinDepartment of Biochemistry, University of Wisconsin-Madison, Madison, WI, 53706, USA.
Natalie M NiemiDepartment of Biochemistry & Molecular Biophysics, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-5174-4005
John M DenuDepartment of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, WI, 53706, USA.
Luigi PuglielliDepartment of Medicine, University of Wisconsin-Madison, Madison, WI, USA.ORCID http://orcid.org/0000-0003-0259-8424
Judith SimcoxCellular and Molecular Biology Graduate Program, University of Wisconsin-Madison, Madison, WI, USA.ORCID http://orcid.org/0000-0001-7350-6342
Dudley W LammingDepartment of Medicine, University of Wisconsin-Madison, Madison, WI, USA. dlamming@medicine.wisc.edu.ORCID http://orcid.org/0000-0002-0079-4467
Funding
WU P&FP30DK020579 · NIDDK · WASHINGTON UNIVERSITY · PI James Alexander Fitzpatrick · 2013 to 2026
$27.1MBiology of Aging and Age-Related Diseases Training GrantT32AG000213 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI Rozalyn M. Anderson, Sanjay Asthana · 1991 to 2026
$9.9MIntegrated Training For Physician-ScientistsT32GM140935 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI Anna Huttenlocher, Jeniel E Nett · 2021 to 2026
$6.5MSpastic paraplegia, neurodegeneration and autism: possible role for AT- 1/SLC33A1?R01NS094154 · NINDS · UNIVERSITY OF WISCONSIN-MADISON · PI Luigi Puglielli · 2015 to 2026
$4.3MCreating a region- specific biomolecular atlas of the brain of Alzheimer’s diseaseR01AG078794 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI LINGJUN LI, Luigi Puglielli · 2022 to 2026
$3.7MThe regulation of health and longevity by branched-chain amino acidsR01AG056771 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI Dudley William Lamming · 2018 to 2026
$3.1MUniversity of Wisconsin Building Interdisciplinary Research Careers in Women's Health (BIRCWH) Scholars ProgramK12HD101368 · NICHD · UNIVERSITY OF WISCONSIN-MADISON · PI BARROILHET, LISA M, BURNSIDE, ELIZABETH S · 2020 to 2023
$2.9MDynamics and molecular mechanisms linking metabolism and the epigenomeR35GM149279 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI JOHN M DENU · 2023 to 2026
$2.8MThe regulation of cancer and aging by methionineR01AG084156 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI VINCENT L. CRYNS, JOHN M DENU · 2023 to 2026
$2.5MThe regulation of health and longevity by branched-chain amino acidsRF1AG056771 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI LAMMING, DUDLEY WILLIAM · 2023 to 2023
$2.1MComparative analysis of geroprotective interventions in established and novel mouse models of Alzheimer's diseaseR01AG062328 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI LAMMING, DUDLEY WILLIAM, MERRINS, MATTHEW J. · 2018 to 2022
$2.0MSafer mTOR inhibition for human geroprotectionU01AG081482 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI Adam R Konopka, Dudley William Lamming · 2023 to 2026
$1.8MAlzheimer's Association 23AARG-1029665BLRD VA I01 BX004031BLRD VA IS1 BX005524NIA NIH HHS F31 AG066311NIA NIH HHS F31 AG081115NIA NIH HHS F31 AG082504NIA NIH HHS F32 AG077916NIA NIH HHS R01 AG056771NIA NIH HHS R01 AG062328NIA NIH HHS R01 AG078794NIA NIH HHS R01 AG084156NIA NIH HHS R21 AG061635NIA NIH HHS R56 AG056771NIA NIH HHS RF1 AG056771NIA NIH HHS T32 AG000213NIA NIH HHS U01 AG081482NICHD NIH HHS K12 HD101368NIDDK NIH HHS P30 DK020579NIDDK NIH HHS R01 DK125859NIDDK NIH HHS R01 DK133479NIGMS NIH HHS R01 GM148487NIGMS NIH HHS R35 GM149279NIGMS NIH HHS R35 GM151130NIGMS NIH HHS T32 GM140935NINDS NIH HHS R01 NS094154U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) DK125859U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) R01DK133479U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R35GM151130U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) AG056771, AG062328, AG061635, AG081482, AG084156U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) AG082504U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) F31AG081115
Abstract
Dietary protein is a critical regulator of metabolic health and aging. Low protein diets are associated with healthy aging in humans, and dietary protein restriction extends the lifespan and healthspan of mice. In this study, we examined the effect of protein restriction (PR) on metabolic health and the development and progression of Alzheimer's disease (AD) in the 3xTg mouse model of AD. Here, we show that PR promotes leanness and glycemic control in 3xTg mice, specifically rescuing the glucose intolerance of 3xTg females. PR induces sex-specific alterations in circulating and brain metabolites, downregulating sphingolipid subclasses in 3xTg females. PR also reduces AD pathology and mTORC1 activity, increases autophagy, and improves the cognition of 3xTg mice. Finally, PR improves the survival of 3xTg mice. Our results suggest that PR or pharmaceutical interventions that mimic the effects of this diet may hold promise as a treatment for AD.
Indexed as
Alzheimer DiseaseBrainDiet, Protein-RestrictedDisease Models, AnimalDisease ProgressionMice, TransgenicAnimalsAutophagyCognitionFemaleGlucose IntoleranceHumansMaleMechanistic Target of Rapamycin Complex 1MiceMice, Inbred C57BLMechanistic Target of Rapamycin Complex 1Sphingolipids
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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.