Multi-omics research in sarcopenia: Current progress and future prospects

Liu, Jiachen; Dong, Shanshan; Shen, Hui; Yang, Dan-Yue; Chen, Binbin; Ma, Xueying; Yan, Peng; Xiao, Hong‐Mei; Deng, Hong‐Wen

doi:10.1016/j.arr.2022.101576

Cited by 37 publications

(27 citation statements)

References 154 publications

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“…For the studies [ 12 , 32–35 ] performed the plasma proteome analysis in which participants with the condition of sarcopenia or frailty or muscle weakness were recruited, the reported differential expression proteins ( N = 178) were included. Additionally, from the muscular proteome analysis studies [ 13 , 36 ] and review articles [ 37–41 ], we also collected the proteins associated with sarcopenia ( N = 216) not reported in previous plasma studies. We also searched the PubMed database with the keywords as ((‘sarcopenia’) OR (‘frailty’) OR (‘muscle weakness’)) AND (‘biomarker’).…”

Section: Methodsmentioning

confidence: 99%

Potential therapeutic targets for sarcopenia identified by Mendelian randomisation

et al. 2023

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Background Identifying sarcopenia’s causally associated plasma proteins would provide potential therapeutic targets. Methods We screened out sarcopenia-related proteins with genome-wide association studies (GWAS) summary data and cis-protein loci genetic instruments. Summary data of sarcopenia were obtained from a GWAS of 256,523 Europeans aged 60 years and over. The causal effects of the proteins were investigated by cis-Mendelian Randomisation (MR) and multiverse sensitivity analysis. We also explored the robust proteins’ causal associations with appendicular lean mass (ALM) and surveyed their druggability and clinical development activities. Results In sum, 60 proteins from plasma proteome analysis studies and 12 from other studies were enrolled for MR analysis. In the whole population, four proteins (HPT, AT1B2, ISLR2 and TNF12) showed causal associations with the risk of sarcopenia according to the European Working Group on Sarcopenia in Older People (EWGSOP) criterion. In the female population, AT1B2 and TNFSF12 revealed causal associations with sarcopenia risk according to the EWGSOP criterion; HGF revealed a negative association according to the National Institutes of Health criterion. All of them were druggable, and the inhibitors of TNF12 and HGF were evaluated in clinical trials for other diseases. TNF12 also revealed a negative causal association with ALM, whereas HGF was positively causally associated with ALM. Conclusions Five druggable plasma proteins revealed causal associations with sarcopenia in the whole or female populations. TNF12 and HGF were the targets of therapeutic agents evaluated in clinical trials, and they were also causally associated with ALM. Our study suggested the potential mechanisms and therapeutic targets for sarcopenia.

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Section: Methodsmentioning

confidence: 99%

Potential therapeutic targets for sarcopenia identified by Mendelian randomisation

et al. 2023

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“…The major pathways of co-expressed enrichment of these two diseases were identified by GSVA, and the results revealed that the enrichment pathway was not only significantly related to epigenetics but also involved in other metabolic diseases and immune-related pathways ( Figure 3 ). This suggests that the gene expression of most metabolic diseases is very similar, and the cause of metabolic diseases may be related to REDOX-related pathways ( 24 ), epigenetic modification, or the mutual regulation of various RNAs ( 25 , 26 ), as well as activating the immune system ( 27 , 28 ).…”

Section: Discussionmentioning

confidence: 99%

Exploration of the core gene signatures and mechanisms between NAFLD and sarcopenia through transcriptomic level

Yu²,

Li³

et al. 2023

Front. Endocrinol.

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IntroductionThe increased prevalence of non-alcoholic fatty liver disease (NAFLD) and sarcopenia among the elderly are facing a significant challenge to the world’s health systems. Our study aims to identify the coexpressed genes in NAFLD and sarcopenia patients.MethodsWe downloaded the transcriptome data of NAFLD tissue from patients, as well as muscle tissues from sarcopenia patients, from the GEO database in order to investigate the shared transcriptional regulation mechanisms between these two diseases. Then, focusing on the genes that were frequently expressed in these diseases, together with GSVA and WGCNA, we utilized a range of analysis methods to identify the main co-expressed genes in both diseases by taking intersections. We investigated these changes after learning that they mostly affected lipid metabolism and oxidative stress injury pathways.ResultsBy analyzing these genes and their interactions with transcription factors and proteins, we were able to identify 8 genes that share common patterns. From these 8 genes, we were possible to forecast potential future medicines. Our research raises the possibility of NAFLD and sarcopenia transcriptome regulatory pathways in aging populations.DiscussionIn conclusion, a complete transcription pattern mapping was carried out in order to identify the core genes, underlying biological mechanisms, and possible therapeutic targets that regulate aging in NAFLD and sarcopenia patients. It provides novel insights and proof in favor of decreasing the increased prevalence of sarcopenia in the elderly caused by NAFLD.

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“…The search for susceptibility genes is another powerful tool to weigh the importance of the many factors involved in muscle disease, and genome-wide association studies in older individuals can identify gene variants that associate with muscle weakness [ 112 ]. Multi-omics approaches that combine the layers of knowledge obtained through genomics, transcriptomics and metabolomics, are powerful tools to unravel complex muscle disease mechanisms, as has recently been elegantly reviewed [ 113 ].…”

Section: Discussionmentioning

confidence: 99%

The Cytokine Growth Differentiation Factor-15 and Skeletal Muscle Health: Portrait of an Emerging Widely Applicable Disease Biomarker

Paepe

2022

IJMS

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Growth differentiation factor 15 (GDF-15) is a stress-induced transforming growth factor-β superfamily cytokine with versatile functions in human health. Elevated GDF-15 blood levels associate with multiple pathological conditions, and are currently extensively explored for diagnosis, and as a means to monitor disease progression and evaluate therapeutic responses. This review analyzes GDF-15 in human conditions specifically focusing on its association with muscle manifestations of sarcopenia, mitochondrial myopathy, and autoimmune and viral myositis. The use of GDF-15 as a widely applicable health biomarker to monitor muscle disease is discussed, and its potential as a therapeutic target is explored.

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Multi-omics research in sarcopenia: Current progress and future prospects

Cited by 37 publications

References 154 publications

Potential therapeutic targets for sarcopenia identified by Mendelian randomisation

Potential therapeutic targets for sarcopenia identified by Mendelian randomisation

Exploration of the core gene signatures and mechanisms between NAFLD and sarcopenia through transcriptomic level

The Cytokine Growth Differentiation Factor-15 and Skeletal Muscle Health: Portrait of an Emerging Widely Applicable Disease Biomarker

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