Pharmacological blockade of TNFα prevents sarcopenia and prolongs survival in aging mice
Open accessAbstract
Sarcopenia is a hallmark of aging. Inflammation due to increased generation of cytokines such as TNFα, IL-1β and IL-6 has been implicated in the pathogenesis of sarcopenia. In skeletal muscle of C57BL/6 mice from 12 until 28 months of age, we observed a progressive reduction of myofiber cross sectional area, loss of type II fibers and infiltration by inflammatory cells. Muscle strength decreased in parallel. Pharmacological TNFα blockade by weekly subcutaneous injection of Etanercept from 16 to 28 months of age prevented atrophy and loss of type II fibers, with significant improvements in muscle function and mice lifespan. The effects on leukocyte recruitment were limited. These results provide a proof of principle that endogenous TNFα is sufficient to cause sarcopenia and to reduce animal survival, and open a novel perspective on novel potential pharmacological treatment strategies based on TNFα blockade to prevent the noxious events associated with aging.
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Etanercept prevents muscle atrophy and extends lifespan in aged mice through preservation of muscle fiber cross-sectional area and type II muscle fibers.
“etanercept, a TNF-α inhibitor, has demonstrated efficacy in preventing muscle atrophy and extending lifespan in aged mice through mechanisms including the preservation of muscle fiber cross-sectional area and type II muscle fibers [27].”
From Exerkines and Sarcopenia: Unveiling the Mechanism Behind Exercise-Induced Mitochondrial Homeostasis (2025) · cites this paper as [27]
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References 45 · Cited by 79
- Authors
- Sciorati, C., Gamberale, R., Monno, A., Citterio, L., Lanzani, C., De Lorenzo, R., Ramirez, G. A., Esposito, A., Manunta, P., Manfredi, A. A., & Rovere-Querini, P.
- Affiliations
- IRCCS Ospedale San Raffaele (IT)
- Division of Immunology, Transplantation and Infectious Diseases, IRCCS Ospedale San Raffaele Scientific Institute, Milan, Italy
- Vita-Salute San Raffaele University (IT)
- Corresponding author
- Sciorati, Clara
- ORCID
- Venue
- Aging
- Publisher
- Impact Journals, LLC
- Published
- 2020-11-26
- Volume
- 12
- Issue
- 23
- Pages
- 23497-23508
- ISSN
- 1945-4589 (ISSN-L)
- PMC
- PMC7762456
- OpenAlex
- W3106971492
- Cited by
- 79
- References
- 45
- Citations by year
- 2026: 13 · 2025: 15 · 2024: 16 · 2023: 21 · 2022: 10 · 2021: 4
- FWCI
- 2.84
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- cc-by
- Locations
- Aging (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion, cc-by)
- Funders
- Fondazione Cariplo (2016-0980)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- sarcopenia, TNF-α, etanercept, skeletal muscle atrophy, fast-twitch muscle, muscle strength, lifespan, inflammation, leukocyte recruitment, myofiber cross-sectional area, cytokines
- MeSH terms
- Etanercept, Tumor Necrosis Factor Inhibitors, Age Factors, Animals, Chemotaxis, Leukocyte, Disease Models, Animal, Female, Mice, Inbred C57BL, Tumor Necrosis Factor-alpha, Muscle, Skeletal, Muscle Strength, Sarcopenia
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