ArticleAging cell2016
Calpain inhibition rescues troponin T3 fragmentation, increases Cav1.1, and enhances skeletal muscle force in aging sedentary mice.
Article in Aging cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 31 citations in OpenAlex.
- Troponin: biology, molecular mechanisms, and multidimensional clinical applications.Molecular biomedicine · 2026Review
- The actively secreted plasma extracellular vesicle troponin (ASPECT) study: circulating troponin in extracellular vesicles across cardiovascular disease cohorts.Biomarker research · 2026Article
- Review
- Exploration of Pathogenesis and Cutting-Edge Treatment Strategies of Sarcopenia: A Narrative Review.Clinical interventions in aging · 2025Review
- Effects of aging on calcium channels in skeletal muscle.Frontiers in molecular biosciences · 2025Review
- Role of the interaction between troponin T and AMP deaminase by zinc bridge in modulating muscle contraction and ammonia production.Molecular and cellular biochemistry · 2024Review
- Non-Canonical Localization of Cardiac Troponins: Expanding Functions or Causing Pathologies?International journal of molecular sciences · 2024Review
- Skeletal muscle-specific calpastatin overexpression mitigates muscle weakness in aging and extends life span.Journal of applied physiology (Bethesda, Md. : 1985) · 2021Article
- Screening and Identification of Muscle-Specific Candidate GenesFrontiers in veterinary science · 2021Article
- Cardiomyocyte nuclearity and ploidy: when is double trouble?Journal of muscle research and cell motility · 2020Article
- Implications of the complex biology and micro-environment of cardiac sarcomeres in the use of high affinity troponin antibodies as serum biomarkers for cardiac disorders.Journal of molecular and cellular cardiology · 2020Review
- The loss of slow skeletal muscle isoform of troponin T in spindle intrafusal fibres explains the pathophysiology of Amish nemaline myopathy.The Journal of physiology · 2019Article
- The sympathetic nervous system regulates skeletal muscle motor innervation and acetylcholine receptor stability.Acta physiologica (Oxford, England) · 2019Article
- Changes in Redox Signaling in the Skeletal Muscle with Aging.Oxidative medicine and cellular longevity · 2019Review
- Familial Dilated Cardiomyopathy Associated With a Novel Combination of Compound HeterozygousFrontiers in physiology · 2019Article
- Role of the HPRG Component of Striated Muscle AMP Deaminase in the Stability and Cellular Behaviour of the Enzyme.Biomolecules · 2018Review
- Troponin T3 associates with DNA consensus sequence that overlaps with p53 binding motifs.Experimental gerontology · 2018Article
- Skeletal muscle performance and ageing.Journal of cachexia, sarcopenia and muscle · 2018Review
- Troponin through the looking-glass: emerging roles beyond regulation of striated muscle contraction.Oncotarget · 2018Review
- Cardiac troponin T and fast skeletal muscle denervation in ageing.Journal of cachexia, sarcopenia and muscle · 2017Article
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
Loss of strength in human and animal models of aging can be partially attributed to a well-recognized decrease in muscle mass; however, starting at middle-age, the normalized force (force/muscle cross-sectional area) in the knee extensors and single muscle fibers declines in a curvilinear manner. Strength is lost faster than muscle mass and is a more consistent risk factor for disability and death. Reduced expression of the voltage sensor Ca(2+) channel α1 subunit (Cav1.1) with aging leads to excitation-contraction uncoupling, which accounts for a significant fraction of the decrease in skeletal muscle function. We recently reported that in addition to its classical cytoplasmic location, fast skeletal muscle troponin T3 (TnT3) is fragmented in aging mice, and both full-length TnT3 (FL-TnT3) and its carboxyl-terminal (CT-TnT3) fragment shuttle to the nucleus. Here, we demonstrate that it regulates transcription of Cacna1s, the gene encoding Cav1.1. Knocking down TnT3 in vivo downregulated Cav1.1. TnT3 downregulation or overexpression decreased or increased, respectively, Cacna1s promoter activity, and the effect was ablated by truncating the TnT3 nuclear localization sequence. Further, we mapped the Cacna1s promoter region and established the consensus sequence for TnT3 binding to Cacna1s promoter. Systemic administration of BDA-410, a specific calpain inhibitor, prevented TnT3 fragmentation, and Cacna1s and Cav1.1 downregulation and improved muscle force generation in sedentary old mice.
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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.