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Vastus lateralis muscle aging

ABSTRACT: Development of a method to identify age-regulated expression trends in skeletql muscles and study the underlying molecular processes of the age_associated progressive changes in skeletal muscles. See abstract from associated manuscript below : Aging is characterized by progressive tissue degeneration and it is associated with genome-wide changes of mRNA expression profiles. Therefore, it is expected that age-regulated changes in expression profiles could describe the process of aging. We have developed a robust and unbiased methodology to identify age-regulated expression trends in cross-sectional data sets from healthy donors. Our analysis in four different tissues reveals that in brain cortex and Vastus lateralis muscles, two major age-associated expression inclinations were found, one during midlife and one in elderly. In kidney medulla and cortex, however, transcriptional changes were found only in elderly. In concurrence with increased degeneration in aged tissue, the elderly-associated expression changes are predominantly downwards. Our results suggest that a non-linear trend describes the aging process, and can be the result of inclinations of gene expression at two distinct age-positions affecting different molecular and cellular processes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE40645 | GEO | 2012/12/03

SECONDARY ACCESSION(S): PRJNA174464

REPOSITORIES: GEO

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Vastus lateralis muscle aging

Project description:Development of a method to identify age-regulated expression trends in skeletql muscles and study the underlying molecular processes of the age_associated progressive changes in skeletal muscles. See abstract from associated manuscript belowÂ : Aging is characterized by progressive tissue degeneration and it is associated with genome-wide changes of mRNA expression profiles. Therefore, it is expected that age-regulated changes in expression profiles could describe the process of aging. We have developed a robust and unbiased methodology to identify age-regulated expression trends in cross-sectional data sets from healthy donors. Our analysis in four different tissues reveals that in brain cortex and Vastus lateralis muscles, two major age-associated expression inclinations were found, one during midlife and one in elderly. In kidney medulla and cortex, however, transcriptional changes were found only in elderly. In concurrence with increased degeneration in aged tissue, the elderly-associated expression changes are predominantly downwards. Our results suggest that a non-linear trend describes the aging process, and can be the result of inclinations of gene expression at two distinct age-positions affecting different molecular and cellular processes. RNA was extracted from vastus lateralis muscles. cDNA synthesis and labeling were preformed with the Illumina cDNA labeling kit.

2012-12-03 | E-GEOD-40645 | biostudies-arrayexpress

Knockdown of the transcription regulators Spt5 and dom in Drosophila photoreceptors results in premature retinal degeneration and transcriptional signature similar to old flies

Project description:Aging is associated with a decline in visual function and increased prevalence of ocular disease, correlating with changes in the transcriptome and epigenome of cells in the eye. Here, we sought to test if age-associated changes in gene expression patterns in the eye directly contribute to the increased risk of retinal degeneration. To do this, we performed a targeted photoreceptor specific RNAi screen in Drosophila to identify gene regulatory factors that result in premature, age-dependent retinal degeneration. From an initial set of 155 RNAi lines each targeting a unique gene and spanning a diverse set of gene regulatory factors, we identified 18 high confidence target genes whose decreased expression in adult photoreceptors leads to premature and progressive retinal degeneration. The 18 target genes were enriched for factors involved in the regulation of transcription initiation, pausing, and elongation, suggesting that these processes are essential for maintaining the health of aging photoreceptors. To identify the genes regulated by these factors, we profiled the photoreceptor transcriptome in a subset of lines. Strikingly, two of the 18 target genes, Spt5 and domino, show substantially similar changes in gene expression to those observed with advanced age. Together, our data suggests that dysregulation of the mechanisms involved in transcription initiation and elongation plays a key role in shaping the transcriptome of aging photoreceptors. Further, our findings indicate that the age-dependent changes in gene expression not only correlate, but might also contribute to increased risk of retinal degeneration.

2023-05-05 | GSE225499 | GEO

Aging laryngeal muscle: shifts in gene expression patterns and function

Project description:Sarcopenia is the decreased muscle mass and weakness associated with aging and a major cause of morbidity and mortality in the elderly. To what extent non-locomotive muscles are susceptible to this condition is unclear. For example, age affects laryngeal function (ventilation, airway protective reflexes, swallowing and phonation). Age-related laryngeal dysfunction may be due to effects on its intrinsic muscles that have a unique phenotype: very small, mostly fast oxidative muscle fibers. For this study, we examined how age alters the functional characteristics and gene expression profile of posterior cricoarytenoid (PCA), an intrinsic laryngeal muscle. PCA muscles from Fischer 344-Brown Norway F1 hybrid rats (6 and 30 months of age) were used for cDNA microarrays, light and electron (EM) microscopy, and in vitro contractile function. Histological analyses demonstrated a ~40% increase in mean PCA fiber size and in the number of fibers with low myosin ATPase activity. There was also evidence of ragged-red fibers, a hallmark of mitochondrial dysfunction. In turn, mitochondrial volume density, determined by EM, was significantly higher in PCA muscles at 30 months (43% vs. 21% at 6 months). In vitro function showed a decrease in velocity of unloaded shortening at 30 months. Finally, cDNA microarrays demonstrated a transcriptome shift in PCA muscle with age. Gene classes with the largest changes were: signal transduction, transcription factors, and metabolic enzymes. These data demonstrate that PCA muscles are significantly altered by age. Moreover, the observed changes in muscle fiber size, mitochondrial content and gene expression profile suggest that the PCA response to age diverges from that seen in more typical skeletal muscles. Keywords: aging, time course

2005-09-17 | GSE3310 | GEO

Deep proteome of aging skeletal muscles reveals Smoc2 as a modulator of satellite cell regenerative capacity

Project description:During aging, the number and functionality of muscle stem cells (MuSCs) decreases leading to impaired regeneration of aged skeletal muscle. In addition to intrinsic changes in aged MuSCs, extracellular matrix (ECM) proteins deriving from other cell types, e.g., fibrogenic-adipogenic progenitor cells (FAPs), contribute to the aging phenotype of MuSCs and impaired regeneration in the elderly. So far, no comprehensive analysis on how age-dependent changes in the whole skeletal muscle proteome affect MuSC function have been conducted. Here, we investigated age-dependent changes in the proteome of different skeletal muscle types by applying deep quantitative mass spectrometry. We identified 183 extracellular matrix proteins that show different abundances in skeletal muscles of old mice. By integrating single cell sequencing data, we reveal that transcripts of those ECM proteins are mainly expressed in FAPs, suggesting that FAPs are the main contributors to ECM remodelling during aging. We functionally investigated one of those ECM molecules, namely Smoc2, which is aberrantly expressed during aging. We show that Smoc2 levels are elevated during regeneration and that its accumulation in the aged MuSC niche causes impairment of MuSCs function through constant activation of integrin/MAPK signaling. In vivo, supplementation of exogenous Smoc2 hampers the regeneration of young muscles following serial injuries, leading to a phenotype reminiscent of regenerating aged skeletal muscle. Taken together, we provide a comprehensive resource of changes in the composition of the ECM of aged skeletal muscles, we pinpoint the cell types driving these changes, and we identify a new niche protein causing functional impairment of MuSCs thereby hampering the regeneration capacity of skeletal muscles.

2021-11-25 | PXD015728 | Pride

Deep proteome of aging skeletal muscles reveals Smoc2 as a modulator of satellite cell regenerative capacity

2021-11-25 | PXD015616 | Pride

Leucocyte small nucleolar RNA and microRNA expression data from healthy control subjects of different age

Project description:It has been observed that immune cell deterioration occurs in the elderly, as well as a chronic low-grade inflammation called inflammaging. These cellular changes must be driven by numerous changes in gene expression and in fact, both protein-coding and non-coding RNA expression alterations have been observed in peripheral blood mononuclear cells from elder people. In the present work we have studied the expression of small non-coding RNA (microRNA and small nucleolar RNA -snoRNA-) from healthy individuals from 24 to 79 years old. We have observed that the expression of 69 non-coding RNAs (56 microRNAs and 13 snoRNAs) changes progressively with chronological age. According to our results, the age range from 47 to 54 is critical given that is the period when the expression trend (increasing or decreasing) of age-related small non-coding RNAs is more pronounced. Furthermore, age-related miRNAs regulate genes that are involved in immune, cell cycle and cancer-related processes, which had already been associated to human aging. Therefore, human aging could be studied as a result of progressive molecular changes, and different age ranges should be analysed to cover the whole aging process.

2016-11-30 | GSE89042 | GEO

Human skeletal muscle CD90+ fibro-adipogenic progenitors are associated with muscle degeneration in type 2 diabetic patients

Project description:Aging and type 2 diabetes mellitus (T2DM) are associated with impaired skeletal muscle function and degeneration of the skeletal muscle microenvironment. However, the origin and mechanisms underlying the degeneration are not well described in human skeletal muscle. Here we show that skeletal muscles of T2DM patients exhibit pathological degenerative remodeling of the extracellular matrix that was associated with a selective increase of a subpopulation of fibro-adipogenic progenitors (FAPs) marked by expression of THY1 (CD90).

| EGAS00001005599 | EGA

MiRNA expression profiling of skeletal muscles in aged rodents

Project description:Skeletal muscle atrophy is one of the critical issues which elderly people face. The precise mechanism underlying muscle atrophy during aging is not fully understood. In order to identify miRNA whose expression is changed in age-associated muscle atrophy, we performed miRNA expression profiling of skeletal muscles in young and aged rats. Microarray analysis revealed differential miRNA expression in EDL and soleus muscles of aged rats compared with those of young rats. We next investigated whether the age-associated changes of miRNA expression observed in rats were recapitulated in mice and found that the expression level of miR-206 in EDL muscle and that of miR-196a in EDL and soleus muscles were respectively higher and lower in aged rodents than in young rodents. In mouse C2C12 myoblasts and myotubes, introduction of miR-196a decreased the protein level of Forkhead-box transcription factor Foxo1, a known target of miR-196a, indicating that miR-196a may regulate Foxo1 expression also in skeletal muscles. Furthermore, miR-196a overexpression exacerbated cell death caused by an exposure to hydrogen peroxide. Lastly, we demonstrated that expression of Foxo1 was elevated in EDL and soleus muscles of aged mice compared with those of young mice. These results suggest that miRNAs are involved in skeletal muscle atrophy during aging and that decreased miR-196a expression may protect skeletal muscle cells from oxidative stress in part through induction of Foxo1.

2016-08-31 | GSE70990 | GEO

Novel Sarcopenia-related Alterations in Sarcomeric Protein Post-translational Modifications in Skeletal Muscles Identified by Top-down Proteomics

Project description:Sarcopenia, the age-related loss of skeletal muscle mass and strength, is a significant cause of morbidity in the elderly and is a major burden on health care systems. Unfortunately, the underlying molecular mechanisms in sarcopenia remain poorly understood. Herein, we utilized top-down proteomics to elucidate sarcopenia-related changes in the fast- and slow-twitch skeletal muscles of aging rats with a focus on the sarcomeric proteome, which includes both myofilament and Z-disc proteins--the proteins that constitute the contractile apparatuses.

2017-06-12 | MSV000081157 | MassIVE

Transcription profiling by array of human bone marrow hematopoietic stem cells from healthy young and elderly individuals

Project description:In the human hematopoietic system, aging is associated with decreased bone marrow cellularity, decreased adaptive immune system function, and increased incidence of anemia and other hematological disorders and malignancies. Recent studies in mice suggest that changes within the hematopoietic stem cell (HSC) population during aging contribute significantly to the manifestation of these age-associated hematopoietic pathologies. While the mouse HSC population has been shown to change both quantitatively and functionally with age, changes in the human HSC and progenitor cell populations during aging have not yet been characterized. Gene expression profiling revealed that aged human HSC transcriptionally up-regulate genes associated with cell cycle, myeloid lineage specification, and myeloid malignancies. These age-associated alterations in the frequency, function, and gene expression profile of human HSC are significantly similar to those changes observed in mouse HSC, suggesting that hematopoietic aging is an evolutionarily conserved process. In order to elucidate the properties of an aged human hematopoietic system that may predispose to age-associated hematopoietic dysfunction, we evaluated HSC and other hematopoietic progenitor populations from healthy, hematologically normal young and elderly human bone marrow samples. We found that aged human HSC increase in frequency, are less quiescent, and exhibit myeloid-biased differentiation potential compared to young HSC.

2011-11-11 | E-GEOD-32719 | biostudies-arrayexpress

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