ArticleScience translational medicine2012
Rapamycin reverses elevated mTORC1 signaling in lamin A/C-deficient mice, rescues cardiac and skeletal muscle function, and extends survival.
Article in Science translational medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 233 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
233 citing papers in PubMed, 1 synthesis or guideline pooled it, 354 citations in OpenAlex.
- Rapamycin, Not Metformin, Mirrors Dietary Restriction-Driven Lifespan Extension in Vertebrates: A Meta-Analysis.Aging cell · 2025Pooled it
- Nuclear membrane disruption in neurodegenerative diseases: Emerging perspectives.Neural regeneration research · 2026Article
- Muscular dystrophy-associated lamin variants disrupt cellular organization through a nucleolar-ribosomal axis.Science advances · 2026Article
- Novel truncating Desmin mutation Arg150Stop disrupts structural integrity and cellular homeostasis by formation of persistent aggregate-like structure.Cell death discovery · 2026Article
- Perinuclear organelle trauma at the nexus of cardiomyopathy pathogenesis arising from loss of functionNucleus (Austin, Tex.) · 2025Review
- LMNA-related cardiomyopathy: From molecular pathology to cardiac gene therapy.Journal of advanced research · 2025Review
- Research progress on programmed cell death of cardiomyocytes in pressure-overload hypertrophic cardiomyopathy.Apoptosis : an international journal on programmed cell death · 2025Review
- Nonsense-Mediated mRNA Decay: Mechanisms and Recent Implications in Cardiovascular Diseases.Cells · 2025Review
- Roadmap for alleviating the manifestations of ageing in the cardiovascular system.Nature reviews. Cardiology · 2025Review
- Mechanisms Underlying Muscle-Related Diseases and Aging: Insights into Pathophysiology and Therapeutic Strategies.Muscles (Basel, Switzerland) · 2025Review
- Mammalian nucleophagy: process and function.Autophagy · 2025Review
- Enhancing immunity during ageing by targeting interactions within the tissue environment.Nature reviews. Drug discovery · 2025Review
- Malformations of Core M3 on α-Dystroglycan Are the Leading Cause of Dystroglycanopathies.Journal of molecular neuroscience : MN · 2025Review
- Model organisms for investigating the functional involvement of NRF2 in non-communicable diseases.Redox biology · 2025Review
- The Dental and Oral Significance of Hutchinson-Gilford Prfogeria Syndrome : The Dental and Oral Significance of Hutchinson-Gilford Prfogeria Syndrome.Galen medical journal · 2025Review
- A loss of primary cilia by a reduction in mTOR signaling correlates with age-related deteriorations in condylar cartilage.GeroScience · 2024Article
- Dilated Cardiomyopathy - Exploring the Underlying Causes.Medical research archives · 2024Article
- Non-Cell-Autonomous Cardiomyocyte Regulation Complicates Gene Supplementation Therapy forJACC. Basic to translational science · 2024Article
- Sestrin2 serves as a scaffold protein to maintain cardiac energy and metabolic homeostasis during pathological stress.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Review
- SIRT1 Ameliorates Lamin A/C Deficiency-Induced Cardiac Dysfunction by Promoting Mitochondrial Bioenergetics.JACC. Basic to translational science · 2024Article
173 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Mutations in LMNA, the gene that encodes A-type lamins, cause multiple diseases including dystrophies of the skeletal muscle and fat, dilated cardiomyopathy, and progeria-like syndromes (collectively termed laminopathies). Reduced A-type lamin function, however, is most commonly associated with skeletal muscle dystrophy and dilated cardiomyopathy rather than lipodystrophy or progeria. The mechanisms underlying these diseases are only beginning to be unraveled. We report that mice deficient in Lmna, which corresponds to the human gene LMNA, have enhanced mTORC1 (mammalian target of rapamycin complex 1) signaling specifically in tissues linked to pathology, namely, cardiac and skeletal muscle. Pharmacologic reversal of elevated mTORC1 signaling by rapamycin improves cardiac and skeletal muscle function and enhances survival in mice lacking A-type lamins. At the cellular level, rapamycin decreases the number of myocytes with abnormal desmin accumulation and decreases the amount of desmin in both muscle and cardiac tissue of Lmna(-/-) mice. In addition, inhibition of mTORC1 signaling with rapamycin improves defective autophagic-mediated degradation in Lmna(-/-) mice. Together, these findings point to aberrant mTORC1 signaling as a mechanistic component of laminopathies associated with reduced A-type lamin function and offer a potential therapeutic approach, namely, the use of rapamycin-related mTORC1 inhibitors.
Indexed as
Identifiers
What OpenQuestion holds
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.