ArticleThe journals of gerontology. Series A, Biological sciences and medical sciences2020
Differential Effects of Rapamycin and Metformin in Combination With Rapamycin on Mechanisms of Proteostasis in Cultured Skeletal Myotubes.
Article in The journals of gerontology. Series A, Biological sciences and medical sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 19 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Rapamycin, Not Metformin, Mirrors Dietary Restriction-Driven Lifespan Extension in Vertebrates: A Meta-Analysis.Aging cell · 2025Pooled it
- A Computational Model for Determining Labeling Duration in Protein Turnover Studies Using a Single Deuterated Water Labeled Sample.Journal of the American Society for Mass Spectrometry · 2026Article
- Biomechanical strain alters the microRNA cargo of primary myogenic cell-derived extracellular vesicles associated with a differentiation phenotype.Frontiers in cell and developmental biology · 2026Article
- Duplexing metabolic deuterated water-labeled samples using dimethyl labeling to estimate protein turnover rates.Communications chemistry · 2025Article
- Combining In Vivo 2-Photon Imaging with Photoactivatable Fluorescent Labeling Shows Low Rates of Mitochondrial Dynamics in Skeletal Muscle.Medicine and science in sports and exercise · 2025Article
- Deuterium labeling enables proteome-wide turnover kinetics analysis in cell culture.Cell reports methods · 2025Article
- NLRP3 inflammasome: structure, mechanism, drug-induced organ toxicity, therapeutic strategies, and future perspectives.RSC medicinal chemistry · 2025Review
- HSF1 remodels mitochondrial biogenesis and function in cancer cells via TIMM17A.bioRxiv : the preprint server for biology · 2025Article
- Pharmacological reduction of lipid hydroperoxides as a potential modulator of sarcopenia.The Journal of physiology · 2025Article
- Current limitations and future opportunities of tracer studies of muscle ageing.The Journal of physiology · 2025Article
- Phytochemical compound PB125 attenuates skeletal muscle mitochondrial dysfunction and impaired proteostasis in a model of musculoskeletal decline.The Journal of physiology · 2023Article
- The bridge between cell survival and cell death: reactive oxygen species-mediated cellular stress.EXCLI journal · 2023Review
- Evaluation of the Combination of Metformin and Rapamycin in an MPPAdvances in pharmacological and pharmaceutical sciences · 2023Article
- Integrated or Independent Actions of Metformin in Target Tissues Underlying Its Current Use and New Possible Applications in the Endocrine and Metabolic Disorder Area.International journal of molecular sciences · 2021Review
- Tumor burden negatively impacts protein turnover as a proteostatic process in noncancerous liver, heart, and muscle, but not brain.Journal of applied physiology (Bethesda, Md. : 1985) · 2021Article
- A Novel Stable Isotope Approach Demonstrates Surprising Degree of Age-Related Decline in Skeletal Muscle Collagen Proteostasis.Function (Oxford, England) · 2021Article
- TORwards a Victory Over Aging.The journals of gerontology. Series A, Biological sciences and medical sciences · 2020Article
- Metformin May Contribute to Inter-individual Variability for Glycemic Responses to Exercise.Frontiers in endocrinology · 2020Review
- Exercise-Induced Mitohormesis for the Maintenance of Skeletal Muscle and Healthspan Extension.Sports (Basel, Switzerland) · 2019Review
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
mTOR inhibition extends life span in multiple organisms. In mice, when metformin treatment (Met) is added to the mTOR inhibitor rapamycin (Rap), median and maximal life span is extended to a greater degree than with Rap or Met alone. Treatments that extend life span often maintain proteostasis. However, it is less clear how individual tissues, such as skeletal muscle, maintain proteostasis with life span-extending treatments. In C2C12 myotubes, we used deuterium oxide (D2O) to directly measure two primary determinants of proteostasis, protein synthesis, and degradation rates, with Rap or Met+Rap treatments. We accounted for the independent effects of cell growth and loss, and isolated the contribution of autophagy and mitochondrial fission to obtain a comprehensive assessment of protein turnover. Compared with control, both Rap and Met+Rap treatments lowered mitochondrial protein synthesis rates (p < .001) and slowed cellular proliferation (p < .01). These changes resulted in greater activation of mechanisms promoting proteostasis for Rap, but not Met+Rap. Compared with control, both Rap and Met+Rap slowed protein breakdown. Autophagy and mitochondrial fission differentially influenced the proteostatic effects of Rap and Met+Rap in C2C12 myotubes. In conclusion, we demonstrate that Met+Rap did not increase protein turnover and that these treatments do not seem to promote proteostasis through increased autophagy.
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Registered trials
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.