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Skeletal muscle TFEB signaling promotes central nervous system function and reduces neuroinflammation during aging and neurodegenerative disease.
Matthews, Ian; Birnbaum, Allison; Gromova, Anastasia; Huang, Amy W; Liu, Kailin; Liu, Eleanor A; Coutinho, Kristen; McGraw, Megan; Patterson, Dalton C; Banks, Macy T; Nobles, Amber C; Nguyen, Nhat; Merrihew, Gennifer E; Wang, Lu; Baeuerle, Eric; Fernandez, Elizabeth; Musi, Nicolas; MacCoss, Michael J; Miranda, Helen C; La Spada, Albert R; Cortes, Constanza J.
Affiliation
  • Matthews I; Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90007, USA.
  • Birnbaum A; Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90007, USA.
  • Gromova A; Department of Pathology and Laboratory Medicine, UCI Institute for Neurotherapeutics, University of California, Irvine, Irvine, CA 92697, USA.
  • Huang AW; Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90007, USA.
  • Liu K; Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90007, USA.
  • Liu EA; Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90007, USA.
  • Coutinho K; Comprehensive Diabetes Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
  • McGraw M; Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
  • Patterson DC; Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
  • Banks MT; Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
  • Nobles AC; Department of Neurology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
  • Nguyen N; Department of Pathology and Laboratory Medicine, UCI Institute for Neurotherapeutics, University of California, Irvine, Irvine, CA 92697, USA.
  • Merrihew GE; Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
  • Wang L; Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195, USA.
  • Baeuerle E; Department of Pharmacology, University of Texas Health San Antonio, San Antonio, TX 78229, USA; Barshop Institute for Longevity and Aging Studies, University of Texas Health San Antonio, San Antonio, TX 78229, USA; Geriatric Research, Education and Clinical Center, South Texas Veterans Health Care N
  • Fernandez E; Department of Pharmacology, University of Texas Health San Antonio, San Antonio, TX 78229, USA; Barshop Institute for Longevity and Aging Studies, University of Texas Health San Antonio, San Antonio, TX 78229, USA; Geriatric Research, Education and Clinical Center, South Texas Veterans Health Care N
  • Musi N; Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • MacCoss MJ; Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
  • Miranda HC; Department of Genetics and Genome Sciences, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA; Department of Neurosciences, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA; RNA Center, School of Medicine, Case Western Reserve University, Clev
  • La Spada AR; Department of Pathology and Laboratory Medicine, UCI Institute for Neurotherapeutics, University of California, Irvine, Irvine, CA 92697, USA; Department of Neurology and Department of Biological Chemistry, UCI Institute for Neurotherapeutics, University of California, Irvine, Irvine, CA 92697, USA.
  • Cortes CJ; Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90007, USA. Electronic address: cjc_149@usc.edu.
Cell Rep ; 42(11): 113436, 2023 11 28.
Article in En | MEDLINE | ID: mdl-37952157
Skeletal muscle has recently arisen as a regulator of central nervous system (CNS) function and aging, secreting bioactive molecules known as myokines with metabolism-modifying functions in targeted tissues, including the CNS. Here, we report the generation of a transgenic mouse with enhanced skeletal muscle lysosomal and mitochondrial function via targeted overexpression of transcription factor E-B (TFEB). We discovered that the resulting geroprotective effects in skeletal muscle reduce neuroinflammation and the accumulation of tau-associated pathological hallmarks in a mouse model of tauopathy. Muscle-specific TFEB overexpression significantly ameliorates proteotoxicity, reduces neuroinflammation, and promotes transcriptional remodeling of the aged CNS, preserving cognition and memory in aged mice. Our results implicate the maintenance of skeletal muscle function throughout aging in direct regulation of CNS health and disease and suggest that skeletal muscle originating factors may act as therapeutic targets against age-associated neurodegenerative disorders.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Neurodegenerative Diseases Limits: Animals Language: En Journal: Cell Rep Year: 2023 Type: Article Affiliation country: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Neurodegenerative Diseases Limits: Animals Language: En Journal: Cell Rep Year: 2023 Type: Article Affiliation country: United States