Dataset Information

Human myofiber-enriched aging-induced lncRNA FRAIL1 promotes muscle atrophy

ABSTRACT: The loss of skeletal muscle mass during aging is a significant health concern linked to adverse outcomes in older individuals. Understanding the molecular basis of age-related muscle loss is crucial for developing strategies to prevent or reverse this debilitating condition. Long non-coding RNAs (lncRNAs) are a largely uncharacterized class of biomolecules that have been implicated in cellular homeostasis and dysfunction across a wide variety of tissues and cell types. To identify lncRNAs that might contribute to skeletal muscle aging we screened for lncRNAs whose expression was altered in vastus lateralis muscle from older compared to young adults. We identified FRAIL1 as an aging-induced lncRNA with high abundance in human skeletal muscle. In a cohort of healthy young and older adults, skeletal muscle FRAIL1 was most strongly expressed in older females and negatively associated with measures of muscle strength and mass. Forced expression of FRAIL1 in mouse tibialis anterior muscle elicits a dose-dependent reduction in skeletal muscle fiber size that is independent of changes in muscle fiber type. Furthermore, this reduction in muscle size is dependent on an intact region of FRAIL1 that is highly conserved across non-human primates. Unbiased transcriptional and proteomic profiling of the effects of FRAIL1 expression in mouse skeletal muscle revealed widespread changes in mRNA and protein abundance that recapitulate age-related changes in pathways and processes that are known to be altered in aging skeletal muscle. Taken together, these findings shed light on the intricate molecular mechanisms underlying skeletal muscle aging and implicate FRAIL1 in the reduction of muscle mass during this process.

ORGANISM(S): Mus musculus

PROVIDER: GSE249356 | GEO | 2024/02/24

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:A common characteristic of aging is the loss of skeletal muscle (sarcopenia) which can lead to falls and fractures. MicroRNAs (miRNA) are novel post-transcriptional modulators of gene expression with a potential role as a regulator of skeletal muscle mass and function. The purpose of this study was to profile miRNA expression patterns in aging human skeletal muscle using a miRNA array followed by in-depth functional and network analysis. Muscle biopsy samples from 36 men (young: 31Â±2; n=19; older: 73Â±3; n=17) were: 1) analyzed for the expression of miRNAs using a microRNA array 2) validated with Taqman quantitative real-time PCR assays, and 3) identified (and later validated) for potential gene targets using the bioinformatics knowledge base software, Ingenuity Pathways Analysis. We found that 18 miRNAs were differentially expressed in older humans (P<0.05 and >500 expression level). The Let-7 family members, Let-7b and Let-7e, were significantly elevated and further validated in older subjects (P<0.05). Functional and network analysis from Ingenuity determined that gene targets of the Let-7âs were associated with molecular networks involved in cell cycle control such as cellular proliferation and differentiation. We confirmed with real-time PCR that the mRNA expression of the cell cycle regulators, CDK6, CDC25A and CDC34 were downregulated in older subjects compared to the young (P<0.05). These data suggest that aging is characterized by an increased expression of Let-7 family members which may downregulate genes related to cellular proliferation. We propose that the increased Let-7 expression in older human muscle may be an indicator of impaired cell cycle function. We analyzed skeletal muscle biopsy samples from 19 young and 17 older male subjects that have participated in our previous and current research experiments. The subjects were not engaged in any regular exercise training at the time of the enrollment; however they were physically independent and overall healthy. Screening of subjects were performed with clinical history, physical exam, and laboratory tests including complete blood count with differential, liver and kidney function tests, coagulation profile, fasting blood glucose and oral glucose tolerance test, hepatitis B and C screening, HIV test, TSH, urinalysis, and drug screening. All subjects gave informed written consent before participating in the study, which was approved by the Institutional Review Board of the University of Texas Medical Branch (which is in compliance with the Declaration of Helsinki). Once recruited, a dual-energy X-ray absorptiometry (DEXA) scan (Hologic QDR 4500W, Bedford, MA) was performed to measure body composition and lean mass. Study design. All subjects were admitted to the Clinical Research Center the day prior to the experiment, were provided a standardized dinner and were studied following an overnight fast under basal conditions. Subjects were studied during the same time of day to avoid potential circadian changes and refrained from exercise 48h prior to study participation. A muscle biopsy was obtained from the vastus lateralis of the leg. The biopsy was performed using a 5 mm BergstrÃ¶m biopsy needle, under sterile procedure and local anesthesia (1% lidocaine). Muscle biopsy sample was immediately blotted and frozen in liquid nitrogen and stored at -80oC until analysis. The muscle biopsy sample was used for microRNA and gene analysis.

Dataset Information

Human myofiber-enriched aging-induced lncRNA FRAIL1 promotes muscle atrophy

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets