Skeletal muscle transcriptome in healthy aging.
Ontology highlight
ABSTRACT:
SUBMITTER: Tumasian RA
PROVIDER: S-EPMC8016876 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Healthy human skeletal muscle samples were processed and analyzed to infer age associated skeletal muscle changes
2021-01-08 | GSE164471 | GEO
Project description:Skeletal Muscle Transcriptome in Healthy Aging
| PRJNA690800 | ENA
Project description:Circadian disruption aggravates age-related decline and mortality. However, it remains unclear whether circadian enhancement can retard aging in mammals. We previously reported that the small molecule Nobiletin (NOB) activates ROR (retinoid acid receptor-related orphan receptor) nuclear receptors to potentiate circadian oscillation and protect against metabolic dysfunctions. Here we show that NOB significantly improves metabolic fitness in naturally aged mice fed with a regular diet (RD). Furthermore, NOB enhances healthy aging in mice fed with a high-fat diet (HF). In HF skeletal muscle, the NOB-ROR axis broadly activates genes for mitochondrial respiratory chain complexes (MRCs) and fortifies MRC activity and architecture, including Complex II activation and supercomplex formation. These mechanisms coordinately lead to a dichotomous mitochondrial optimization, namely increased ATP production and reduced ROS levels. Together, our study illustrates a focal mechanism by a clock-targeting pharmacological agent to optimize skeletal muscle mitochondrial respiration and promote healthy aging in metabolically stressed mammals.
| S-EPMC6713763 | biostudies-literature
Project description:Skeletal muscle aging is a major cause of disability and frailty in the elderly. The progressive impairment of skeletal muscle function with aging was recently linked to a disequilibrium between damage and repair. Macrophages participate in muscle tissue repair, first as pro-inflammatory M1 subtype and then as anti-inflammatory M2 subtype. However, information on the presence of macrophages in skeletal muscle is still sporadic and the effect of aging on macrophage phenotype remains unknown. In this study, we sought to characterize the polarization status of macrophages in skeletal muscle of persons across a wide range of ages. We found that most macrophages in human skeletal muscle are M2, and that this number increased with advancing age. On the contrary, M1 macrophages declined with aging, making the total number of macrophages invariant with older age. Notably, M2 macrophages colocalized with increasing intermuscular adipose tissue (IMAT) in aging skeletal muscle. Similarly, aged BALB/c mice showed increased IMAT and M2 macrophages in skeletal muscle, accompanied by slightly increased collagen protein production. Collectively, we report that polarization of macrophages to the major M2 subtype is associated with IMAT and propose that increased M2 in aged skeletal muscle may impact upon muscle metabolism associated with aging.
| S-EPMC6826159 | biostudies-literature
Project description:There are functional benefits to exercise in muscle, even when performed late in life, but the contributions of epigenetic factors to late-life exercise adaptation are poorly defined. Using reduced representation bisulfite sequencing (RRBS), ribosomal DNA (rDNA) and mitochondrial-specific examination of methylation, targeted high-resolution methylation analysis, and DNAge™ epigenetic aging clock analysis with a translatable model of voluntary murine endurance/resistance exercise training (progressive weighted wheel running, PoWeR), we provide evidence that exercise may mitigate epigenetic aging in skeletal muscle. Late-life PoWeR from 22-24 months of age modestly but significantly attenuates an age-associated shift toward promoter hypermethylation. The epigenetic age of muscle from old mice that PoWeR-trained for eight weeks was approximately eight weeks younger than 24-month-old sedentary counterparts, which represents ~8% of the expected murine lifespan. These data provide a molecular basis for exercise as a therapy to attenuate skeletal muscle aging.
| S-EPMC8761012 | biostudies-literature
Project description:Human aging is associated with skeletal muscle atrophy and functional impairment (sarcopenia). Multiple lines of evidence suggest that mitochondrial dysfunction is a major contributor to sarcopenia. We evaluated whether healthy aging was associated with a transcriptional profile reflecting mitochondrial impairment and whether resistance exercise could reverse this signature to that approximating a younger physiological age. Skeletal muscle biopsies from healthy older (N = 25) and younger (N = 26) adult men and women were compared using gene expression profiling, and a subset of these were related to measurements of muscle strength. 14 of the older adults had muscle samples taken before and after a six-month resistance exercise-training program. Before exercise training, older adults were 59% weaker than younger, but after six months of training in older adults, strength improved significantly (P<0.001) such that they were only 38% lower than young adults. As a consequence of age, we found 596 genes differentially expressed using a false discovery rate cut-off of 5%. Prior to the exercise training, the transcriptome profile showed a dramatic enrichment of genes associated with mitochondrial function with age. However, following exercise training the transcriptional signature of aging was markedly reversed back to that of younger levels for most genes that were affected by both age and exercise. We conclude that healthy older adults show evidence of mitochondrial impairment and muscle weakness, but that this can be partially reversed at the phenotypic level, and substantially reversed at the transcriptome level, following six months of resistance exercise training.
| S-EPMC1866181 | biostudies-literature
Project description:Senescence is a cell fate that contributes to multiple aging-related pathologies. Despite profound age-associated changes in skeletal muscle (SkM), whether its constituent cells are prone to senesce has not been methodically examined. Herein, using single cell and bulk RNA-sequencing and complementary imaging methods on SkM of young and old mice, we demonstrate that a subpopulation of old fibroadipogenic progenitors highly expresses p16 Ink4a together with multiple senescence-related genes and, concomitantly, exhibits DNA damage and chromatin reorganization. Through analysis of isolated myofibers, we also detail a senescence phenotype within a subset of old cells, governed instead by p2 Cip1 . Administration of a senotherapeutic intervention to old mice countered age-related molecular and morphological changes and improved SkM strength. Finally, we found that the senescence phenotype is conserved in SkM from older humans. Collectively, our data provide compelling evidence for cellular senescence as a hallmark and potentially tractable mediator of SkM aging.
| S-EPMC9491365 | biostudies-literature
Project description:With age, adult skeletal muscle (SkM) is known to decrease in muscle mass, strength, and functional capacity, a state known as sarcopenia. Here we developed an in vitro three-dimensional (3D) bioengineered senescent SkM tissue using primary human myoblasts. These tissues exhibited the characteristics of atrophied muscle, including expression of senescent genes, decreased number of satellite cells, reduced number and size of myofibers, and compromised metabolism and calcium flux. As a result, senescent SkM tissues showed impaired ability to generate force in response to electrical stimulation compared with young tissues. Furthermore, in contrast to young SkM tissues, senescent tissues failed to regenerate in response to injury, possibly as a result of persistent apoptosis and failure to initiate a proliferation program. Our findings suggest that 3D senescent SkM may provide a powerful model for studying aging and a platform for drug testing and discovery of therapeutic compounds to improve the function of sarcopenic muscle. Impact statement Skeletal muscle (SkM) plays important physiological roles and has significant regenerative capacity. However, aged SkM lose their functionality and regeneration ability. In this article, we present a senescent human bioengineering SkM tissue model that can be used to investigate senescence, metabolic or genetic diseases that inflict SkM, and to test various strategies including novel small molecules that restore muscle function and promote regeneration. One key limitation of two-dimensional cell culture system is the detachment of contractile myotubes from the surface over time, thereby limiting the evaluation of myogenic function. Here we use primary human myoblasts, which exhibit all major hallmarks of aging to mimic the organization and function of native muscle. Using this system, we were able to measure the contractile function, calcium transients, and regeneration capacity of SkM tissues. We also evaluated the response of senescent SkM tissues to injury and their ability to regenerate and recover, compared with "young" tissues. Our results suggest that three-dimensional constructs enable organization of contractile units including myosin and actin filaments, thereby providing a powerful platform for the quantitative assessment of muscle myotubes in response to injury, genetic or metabolic disorders, or pharmacological testing.
| S-EPMC7826440 | biostudies-literature
Project description:The ability of skeletal muscle to regenerate declines significantly with aging. The expression of aryl hydrocarbon receptor nuclear translocator (ARNT), a critical component of the hypoxia signaling pathway, was less abundant in skeletal muscle of old (23-25 months old) mice. This loss of ARNT was associated with decreased levels of Notch1 intracellular domain (N1ICD) and impaired regenerative response to injury in comparison to young (2-3 months old) mice. Knockdown of ARNT in a primary muscle cell line impaired differentiation in vitro. Skeletal muscle-specific ARNT deletion in young mice resulted in decreased levels of whole muscle N1ICD and limited muscle regeneration. Administration of a systemic hypoxia pathway activator (ML228), which simulates the actions of ARNT, rescued skeletal muscle regeneration in both old and ARNT-deleted mice. These results suggest that the loss of ARNT in skeletal muscle is partially responsible for diminished myogenic potential in aging and activation of hypoxia signaling holds promise for rescuing regenerative activity in old muscle.
| S-EPMC7756517 | biostudies-literature
Project description:As widely distributed domestic animals, sheep are an important species and the source of mutton. In this study, we aimed to evaluate the regulatory lncRNAs associated with muscle growth and development between high production mutton sheep (Dorper sheep and Qianhua Mutton Merino sheep) and low production mutton sheep (Small-tailed Han sheep). In total, 39 lncRNAs were found to be differentially expressed. Using co-expression analysis and functional annotation, 1,206 co-expression interactions were found between 32 lncRNAs and 369 genes, and 29 of these lncRNAs were found to be associated with muscle development, metabolism, cell proliferation and apoptosis. lncRNA-mRNA interactions revealed 6 lncRNAs as hub lncRNAs. Moreover, three lncRNAs and their associated co-expressed genes were demonstrated by cis-regulatory gene analyses, and we also found a potential regulatory relationship between the pseudogene lncRNA LOC101121401 and its parent gene FTH1. This study provides a genome-wide resolution of lncRNA and mRNA regulation in muscles from mutton sheep.
| S-EPMC5899421 | biostudies-literature