Accession PRJCA008759
Title Single-nucleus Transcriptomic Atlas Reveals a Geroprotective Role of FOXO3-SESN1 Axis in Counteracting Primate Skeletal Muscle Aging
Relevance Model organism
Data types Raw sequence reads
Single cell sequencing
Organisms Macaca fascicularis
Mus musculus
Description An age-dependent loss of skeletal muscle mass and function is prominent features for sarcopenia as well as a major risk factor for many other metabolic diseases in the elders. However, a lack of systematic interrogation of aging effects on multinucleated muscle fibers and mononuclear interstitial cells hinders comprehensive understanding of primate skeletal muscle aging. Here, we first systemically depicted phenotypic and transcriptomic features of non-human primate skeletal muscle aging. Through establishment of the single-nucleus transcriptomic atlas of NHP muscle aging, we annotated 14 nuclear subtypes including a variety of myonuclei within the muscle fibers and non-myogenic mononuclear cells. Transcriptional network pinpointed FOXO3 as the prominent downregulated transcription factor in aged NHP skeletal muscle. Knockout of FOXO3 accelerated human myotube senescence via transcriptionally inactivation of a muscle protector SESN1. In contrast, activation of SESN1 or treatment with recombinant human protein SESN1 rescued the premature senescent phenotype of human myotube and promoted muscle regeneration in vivo. Altogether, our findings portray the single-cell transcriptomic landscape of the primate muscle aging and uncover the vital role of FOXO3-SESN1 axis in counteracting human myotube senescence, providing potential biomarkers for the clinical diagnosis of human skeletal muscle aging and targets for developing novel therapeutic interventions to treat aging-related disorders.
Sample scope Multispecies
Release date 2022-11-25
Grants
Agency program Grant ID Grant title
No funding support
Submitter Guanghui    Liu  (ghliu@ioz.ac.cn)
Organization Institute of Zoology, Chinese Academy of Sciences
Submission date 2022-03-20

Project Data

Resource name Description
BioSample (16)  show -
GSA (1) -
CRA006505 Single-nucleus profiling unveils a geroprotective role of the FOXO3 in primate skeletal muscle aging