Cited by 124Sirtuins and Resveratrol in MedicineGenetics, Aging, and Longevity in Model OrganismsDietary Effects on Health

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A Dietary Regimen of Caloric Restriction or Pharmacological Activation of SIRT1 to Delay the Onset of Neurodegeneration

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Gräff, Johannes, Kahn, Martin, Samiei, Alireza, Gao, Jun, Ota, Kristie T., Rei, Damien, Tsai, Li-Huei·2013·The Journal of Neuroscience

DOI 10.1523/jneurosci.5657-12.2013PMC PMC3775567

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Abstract

Caloric restriction (CR) is a dietary regimen known to promote lifespan by slowing down the occurrence of age-dependent diseases. The greatest risk factor for neurodegeneration in the brain is age, from which follows that CR might also attenuate the progressive loss of neurons that is often associated with impaired cognitive capacities. In this study, we used a transgenic mouse model that allows for a temporally and spatially controlled onset of neurodegeneration to test the potentially beneficial effects of CR. We found that in this model, CR significantly delayed the onset of neurodegeneration and synaptic loss and dysfunction, and thereby preserved cognitive capacities. Mechanistically, CR induced the expression of the known lifespan-regulating protein SIRT1, prompting us to test whether a pharmacological activation of SIRT1 might recapitulate CR. We found that oral administration of a SIRT1-activating compound essentially replicated the beneficial effects of CR. Thus, SIRT1-activating compounds might provide a pharmacological alternative to the regimen of CR against neurodegeneration and its associated ailments.

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1 retracted

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Authors: Gräff, J., Kahn, M., Samiei, A., Gao, J., Ota, K. T., Rei, D., & Tsai, L.-H.
Affiliations: Howard Hughes Medical Institute (US)
Broad Institute (US)
Corresponding author: Tsai, Li-Huei
ORCID: Gräff, Johannes
Kahn, Martin
Gao, Jun
Rei, Damien
Tsai, Li-Huei
Venue: The Journal of Neuroscience
Publisher: Society for Neuroscience
Published: 2013-05-22
Volume: 33
Issue: 21
Pages: 8951-8960
ISSN: 0270-6474 (ISSN-L)
1529-2401
DOI: 10.1523/jneurosci.5657-12.2013
PMC: PMC3775567
OpenAlex: W2085431927
Cited by: 124
References: 46
Citations by year: 2026: 1 · 2025: 6 · 2024: 2 · 2023: 7 · 2022: 10 · 2021: 13 · 2020: 10 · 2019: 11 · 2018: 6 · 2017: 18 · 2016: 11 · 2015: 15 · 2014: 12 · 2013: 2
FWCI: 6.22
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-sa
creativecommons.org/licenses/by-nc-sa/4.0/ (vor, 184 d)
Locations: Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
Funders: Howard Hughes Medical Institute
Glenn Foundation for Medical Research
Fondation pour la Recherche Médicale
National Institutes of Health (AG027916, PO1 AG027916)
National Institute on Aging (P01AG027916)
Topics: Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Health Sciences › Medicine › Physiology (medical) › Dietary Effects on Health
Keywords: caloric restriction, SIRT1, neurodegeneration, synaptic loss, cognitive impairment, lifespan extension, SIRT1 activators, transgenic mouse model, age-related neurodegeneration, dietary intervention
MeSH terms: Analysis of Variance, Animals, Atrophy, Brain, Cognition Disorders, Disease Models, Animal, Double-Blind Method, Female, Male, Memory Disorders, Mice, Transgenic, Nerve Tissue Proteins, Phosphopyruvate Hydratase, Phosphotransferases, Piperidines, Synapses, Thiazoles, Vitamin E, Case-Control Studies, Tumor Suppressor Protein p53, Silver Staining, Long-Term Potentiation, Neurodegenerative Diseases, Excitatory Postsynaptic Potentials, Caloric Restriction, Microscopy, Electron, Transmission, Immunoprecipitation, Green Fluorescent Proteins, Cyclin-Dependent Kinase 5, Mice, Sirtuin 1, In Vitro Techniques

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A Dietary Regimen of Caloric Restriction or Pharmacological Activation of SIRT1 to Delay the Onset of Neurodegeneration

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