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Cell Rep ; 42(11): 113436, 2023 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-37952157

RESUMO

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.


Assuntos
Doenças Neurodegenerativas , Camundongos , Animais , Fatores de Transcrição , Doenças Neuroinflamatórias , Músculo Esquelético , Camundongos Transgênicos , Envelhecimento , Sistema Nervoso Central , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos
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