ArticleJournal of cachexia, sarcopenia and muscle2019
4E-BP1 and 4E-BP2 double knockout mice are protected from aging-associated sarcopenia.
Article in Journal of cachexia, sarcopenia and muscle, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 26 citations in OpenAlex.
- Bench to bedside: is rapamycin headed for the docTOR?GeroScience · 2026Review
- Loss of the translational repressor 4E-BP1 promotes skin carcinogenesis.Frontiers in pharmacology · 2026Article
- Neural Cues and Genomic Clues: NGS Insights into Neurogenic Sarcopenia and Muscle Atrophy.International journal of molecular sciences · 2025Review
- Blood flow restriction training: a new approach for preventing and treating sarcopenia in older adults.Frontiers in physiology · 2025Review
- Ursolic Acid Induces Beneficial Changes in Skeletal Muscle mRNA Expression and Increases Exercise Participation and Performance in Dogs with Age-Related Muscle Atrophy.Animals : an open access journal from MDPI · 2024Article
- Canagliflozin shares common mTOR and MAPK signaling mechanisms with other lifespan extension treatments.Life sciences · 2023Article
- 4E-BP1 counteracts human mesenchymal stem cell senescence via maintaining mitochondrial homeostasis.Protein & cell · 2023Article
- Loss of 4E-BPs prevents the hindlimb immobilization-induced decrease in protein synthesis in skeletal muscle.Journal of applied physiology (Bethesda, Md. : 1985) · 2023Article
- Mammalian Target of Rapamycin (mTOR) Signaling at the Crossroad of Muscle Fiber Fate in Sarcopenia.International journal of molecular sciences · 2022Review
- Effects of blood flow restriction (BFR) with resistance exercise on musculoskeletal health in older adults: a narrative review.European review of aging and physical activity : official journal of the European Group for Research into Elderly and Physical Activity · 2022Review
- Animal models of sarcopenia.Aging cell · 2020Review
- mTOR and S6K1 drive polycystic kidney by the control of Afadin-dependent oriented cell division.Nature communications · 2020Article
- Experimental Models of Sarcopenia: Bridging Molecular Mechanism and Therapeutic Strategy.Cells · 2020Review
- 4E-BP1 and 4E-BP2 double knockout mice are protected from aging-associated sarcopenia.Journal of cachexia, sarcopenia and muscle · 2019Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSarcopenia is the loss of muscle mass/function that occurs during the aging process. The links between mechanistic target of rapamycin (mTOR) activity and muscle development are largely documented, but the role of its downstream targets in the development of sarcopenia is poorly understood. Eukaryotic initiation factor 4E-binding proteins (4E-BPs) are targets of mTOR that repress mRNA translation initiation and are involved in the control of several physiological processes. However, their role in skeletal muscle is still poorly understood. The goal of this study was to assess how loss of 4E-BP1 and 4E-BP2 expression impacts skeletal muscle function and homeostasis in aged mice and to characterize the associated metabolic changes by metabolomic and lipidomic profiling.
methodsTwenty-four-month-old wild-type and whole body 4E-BP1/4E-BP2 double knockout (DKO) mice were used to measure muscle mass and function. Protein homeostasis was measured ex vivo in extensor digitorum longus by incorporation of l-[U-
resultsThe 4E-BP1/2 DKO mice exhibited an increase in muscle mass that was associated with increased grip strength (P < 0.05). Protein synthesis was higher under both basal (+102%, P < 0.05) and stimulated conditions (+65%, P < 0.05) in DKO skeletal muscle. Metabolomic and complex lipid analysis of skeletal muscle revealed robust differences pertaining to amino acid homeostasis, carbohydrate abundance, and certain aspects of lipid metabolism. In particular, levels of most free amino acids were lower within the 4E-BP1/2 DKO muscle. Interestingly, although glucose levels were unchanged, differences were observed in the isobaric compound maltitol/lactitol (33-fold increase, P < 0.01) and in several additional carbohydrate compounds. 4E-BP1/2 depletion also resulted in accumulation of medium-chain acylcarnitines and a 20% lower C2/C0 acylcarnitine ratio (P < 0.01) indicative of reduced β-oxidation.
conclusionsTaken together, these findings demonstrate that deletion of 4E-BPs is associated with perturbed energy metabolism in skeletal muscle and could have beneficial effects on skeletal muscle mass and function in aging mice. They also identify 4E-BPs as potential targets for the treatment of sarcopenia.
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