Evidence map›Paper›PMID 33675103›Full record

ArticleAging cell2021

The ketogenic diet preserves skeletal muscle with aging in mice.

Marita A Wallace, Nicholas W Aguirre, George R Marcotte, Andrea G Marshall, Leslie M Baehr, David C Hughes, Karyn L Hamilton, Megan N Roberts, Jose Alberto Lopez-Dominguez, Benjamin F Miller and 2 more

Open access · goldAbstract read
In one paragraph

Article in Aging cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed, 2 pooled it
8.4field-weighted citation impact, top 1% of its field
1 · What the graph read from it

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

64 citing papers in PubMed, 2 syntheses or guidelines pooled it, 86 citations in OpenAlex.

  1. Relationship between Aging and Ketogenic Diet: A Bibliometric Analysis (1995-2025)Endocrine, metabolic & immune disorders drug targets · 2026
    Pooled it
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  3. Review
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  5. Article
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  9. Cellular Senescence in Skeletal Muscle Aging.Endocrinology and metabolism (Seoul, Korea) · 2026
    Review
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  11. Article
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  20. Article

4 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 3 institutions in 1 country.

Marita A WallaceDepartment of Neurobiology, Physiology and Behavior, University of California, Davis, CA, USA.ORCID 0000-0003-1814-2480
Nicholas W AguirreDepartment of Neurobiology, Physiology and Behavior, University of California, Davis, CA, USA.
George R MarcotteDepartment of Neurobiology, Physiology and Behavior, University of California, Davis, CA, USA.
Andrea G MarshallDepartment of Neurobiology, Physiology and Behavior, University of California, Davis, CA, USA.
Leslie M BaehrDepartment of Neurobiology, Physiology and Behavior, University of California, Davis, CA, USA.
David C HughesDepartment of Neurobiology, Physiology and Behavior, University of California, Davis, CA, USA.
Karyn L HamiltonDepartment of Health and Exercise Science, Colorado State University, Fort Collins, CO, USA.
Megan N RobertsDepartment of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA, USA.
Jose Alberto Lopez-DominguezDepartment of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA, USA.
Benjamin F MillerAging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
Jon J RamseyDepartment of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA, USA.
Keith BaarDepartment of Neurobiology, Physiology and Behavior, University of California, Davis, CA, USA.
University of California, Davis · USColorado State University · USOklahoma Medical Research Foundation · US

Funding

TRANSLOCATION OF p66Shc: KINETICS, FUNCTION, APOPTOSISP01AG025532 · NIA · UNIVERSITY OF CALIFORNIA AT DAVIS · PI KIM, KYOUNGMI · 2007 to 2017
$12.1M
Reversing the epigenetic code of aging through ketogenic dietsP01AG062817 · NIA · UNIVERSITY OF CALIFORNIA AT DAVIS · PI CORTOPASSI, GINO A · 2019 to 2023
$11.4M
LAT1 and the development of anabolic resistanceR01AG045375 · NIA · UNIVERSITY OF CALIFORNIA AT DAVIS · PI BAAR, KEITH · 2014 to 2018
$1.7M
NIA NIH HHS P01 AG025532NIA NIH HHS P01 AG062817NIA NIH HHS R01 AG045375
6 · The paper itself

Abstract

The causes of the decline in skeletal muscle mass and function with age, known as sarcopenia, are poorly understood. Nutrition (calorie restriction) interventions impact many cellular processes and increase lifespan and preserve muscle mass and function with age. As we previously observed an increase in life span and muscle function in aging mice on a ketogenic diet (KD), we aimed to investigate the effect of a KD on the maintenance of skeletal muscle mass with age and the potential molecular mechanisms of this action. Twelve-month-old mice were assigned to an isocaloric control or KD until 16 or 26 months of age, at which time skeletal muscle was collected for evaluating mass, morphology, and biochemical properties. Skeletal muscle mass was significantly greater at 26 months in the gastrocnemius of mice on the KD. This result in KD mice was associated with a shift in fiber type from type IIb to IIa fibers and a range of molecular parameters including increased markers of NMJ remodeling, mitochondrial biogenesis, oxidative metabolism, and antioxidant capacity, while decreasing endoplasmic reticulum (ER) stress, protein synthesis, and proteasome activity. Overall, this study shows the effectiveness of a long-term KD in mitigating sarcopenia. The diet preferentially preserved oxidative muscle fibers and improved mitochondrial and antioxidant capacity. These adaptations may result in a healthier cellular environment, decreasing oxidative and ER stress resulting in less protein turnover. These shifts allow mice to better maintain muscle mass and function with age.

Indexed as

AgingAnimalsAntioxidantsDiet, KetogenicEndoplasmic Reticulum StressMaleMiceMice, Inbred C57BLMitochondria, MuscleMuscle, SkeletalNeuromuscular JunctionOrganelle BiogenesisOxidation-ReductionOxidative StressProteasome Endopeptidase ComplexProtein BiosynthesisAntioxidantsProteasome Endopeptidase Complexagingketogenic dietmicesarcopeniaskeletal muscle

Identifiers

PMID33675103
PMCPMC8045940
OpenAlexW3133596913

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.