Cross‐sectional relations of whole‐blood mi<scp>RNA</scp> expression levels and hand grip strength in a community sample

Murabito, Joanne M.; Rong, Jian; Lunetta, Kathryn L.; Huan, Tianxiao; Lin, Honghuang; Zhao, Qiang; Freedman, Jane E.; Tanrıverdi, Kahraman; Levy, Daniel; Larson, Martin G.

doi:10.1111/acel.12622

Cited by 13 publications

(18 citation statements)

References 46 publications

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“…Animal experiment showed that circulating level of miR-19b-3p was associated with cardiac dysfunction level during the development of diabetic cardiomyopathy [20], indicating possible involvement of miR-19b-3p in cardioembolic stroke. As a member of the miR-17 family, miR-20a-5p was well known of the biologic function in hepatic insulin resistance; however its function linked to skeletal muscle as a strength related miRNA emerged recently [21]. Bulent Vatan M reported altered expression of miR-20a-5p in patients with mitral chordae tendineae rupture, suggesting its potential target tissue of myocardium.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA Expression Profiles Identify Biomarker for Differentiating the Embolic Stroke from Thrombotic Stroke

Chen

Jiang

2018

BioMed Research International

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In order to identify potential biomarkers that distinguish the embolic stroke (ES) from thrombotic stroke (TS), a profile of microRNA expression was analyzed. The GSE60319 expression profile was downloaded from the Gene Expression Omnibus (GEO) database. The GEO2R was applied to screen for differentially expressed microRNAs (DEmiRNAs) between the embolic stroke group and thrombotic stroke group. The miRWalk was utilized to predict the target genes of DEmiRNAs. Genes associated with embolic stroke were downloaded from the Comparative Toxicogenomics Database. Cross reference of target genes to disease related genes was conducted to construct the DEmiRNA-gene network. The protein-protein interaction (PPI) network of overlapping genes was evaluated by STRING, using the MCODE and CytoHubba plugin of Cytoscape to identify the modules and hub genes. The enrichment of Kyoto Encyclopedia of Genes and Genomes (KEGG) in modules was performed. There were 30 microRNAs in total identified as DEmiRNAs between embolic stroke and thrombotic stroke groups, of which 8 were upregulated and 22 were downregulated. Among these differentially expressed miRNAs, miR-15a-5p, miR-17-5p, miR-19b-3p, and miR-20a-5p were significantly associated with an ES to TS. Using the miRWalk 3.0 online tool, target genes regulated by DEmiRNAs were predicted. In addition, disease related genes were predicted and compared with target genes of DEmiRNAs. 166 overlapped genes regulated by miR-15a-5p, miR-17-5p, miR-19b-3p, and miR-20a-5p were identified, suggesting their association with diseases that contributed to ES, mainly including atrial fibrillation, mitral valve stenosis, myocardial infarction, and aortic dissection. Therefore, miR-15a-5p, miR-17-5p, miR-19b-3p, and miR-20a-5p were promising candidate biomarkers for differentiating an ES from TS. The PPI network demonstrated that miR-15a-5p, miR-17-5p, miR-19b-3p, and miR-20a-5p were associated with an ES by mainly regulating “CCND1, E2F2, E2F3, ITCH, UBE4A, UBE3C, RBL2, FBXO31, EIF2C4, and EIF2C1”. Furthermore, miR-15a-5p and miR-17-5p may function through “cell cycle, prostate cancer, and small cell lung cancer” while miR-19b-3p and miR-20a-5p function through “insulin resistance, hepatitis B, and viral carcinogenesis” and “vasopressin-regulated water reabsorption”, respectively. However, these results were approached in the manner of bioinformatics analysis; therefore, further verification is required.

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Section: Discussionmentioning

confidence: 99%

MicroRNA Expression Profiles Identify Biomarker for Differentiating the Embolic Stroke from Thrombotic Stroke

Chen

Jiang

2018

BioMed Research International

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“…(28) Handgrip strength was assessed by measuring the highest force generated (in kilograms [kg]) by participants asked to squeeze a JAMAR dynamometer (Sammons Preston/JLW Instruments, Chicago, IL, USA) as hard as possible, three times in each hand. (29) Physical Activity Accelerometry All participants were asked to wear an omnidirectional accelerometer (Actical model no. 198-0200-00; Philips Respironics) on the hip for 8 days during all hours throughout the day and night (except when bathing).…”

Section: Physical Performancementioning

confidence: 99%

Objective physical activity and physical performance in middle-aged and older adults

Lyass

Larson

Tran

et al. 2019

Experimental Gerontology

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Background: Older adults may have difficulty meeting the Physical Activity (PA) Guidelines. A favorable balance between PA and sedentary time (SED) is an important determinant of physical performance in older adults. Our objective was to explore associations of PA/SED with physical performance across mid-older age in adults without overt mobility disability. Methods: Framingham Offspring Study participants free of mobility disability with accelerometry and physical performance data (gait speed, chair stand time, and handgrip strength), were studied in cross-sectional analysis (n=1352). We regressed physical performance on PA level, measured using steps, moderate to vigorous (MV)PA and SED. We stratified by age groups, adjusted for covariates, and modelled MVPA and SED separately and together as predictors. Results: Only 38% of adults 50-64 years and 15% of adults ≥75 years met the PA Guidelines (i.e., 150 minutes MVPA per week). Individuals achieving at least 5 minutes/day of MVPA had 0.062±0.013 m/s greater gait speed and better chair stands and handgrip strength (in women) than those with <5 minutes/day of MVPA (p<0.01) across mid-older age. SED was associated with poorer performance on gait speed and chair stand tests, but results were not significant after adjusting for MVPA (p>0.05). For adults ≥75 years, every 5000 more steps/day related to ~0.045 m/s greater gait speed (p=0.006). Conclusion: Our cross-sectional study demonstrated that, across mid-older adulthood, MVPA related to better physical performance, but in adults ≥75 years, total steps walked associated with better gait speed. These data warrant future research on the impact of PA on physical performance and health outcomes in older age.

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“…Only one study on the epigenetics of hand grip strength has been published so far (Marioni et al 2015) with no significant CpG sites or pathways reported. However, 3 GWAS (Chan et al 2015, Matteini et al 2016 and Willems et al 2017), 2 TWAS (Harries et al 2012 and Pilling et al 2016) and 1 genome-wide miRNA study (Murabito et al 2017) have explored hand grip strength. None of these studies report overlapping genes among their top findings, and none of the suggestive genes of the present study were reported in these studies, neither among the top findings nor among the nominal significant genes reported by Harries et al (2012), Chan et al (2015), and Matteini et al (2016).…”

Section: Discussionmentioning

confidence: 99%

“…They identified 208 differentially expressed genes, half of which were novel in muscle-related literature, thus warranting future work on mechanisms underlying these associations (Pilling et al 2016). Recently, Murabito et al (2017) examined the association of 229 whole-blood microRNAs (miRNAs) with hand grip strength in a population of 5668 individuals aged 24–90 years. The study identified 93 significant miRNAs, for which the potential gene targets were involved in biological pathways of importance for muscle and aging (e.g.…”

Section: Introductionmentioning

confidence: 99%

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Epigenome-wide exploratory study of monozygotic twins suggests differentially methylated regions to associate with hand grip strength

Soerensen

Debrabant

et al. 2019

Biogerontology

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Hand grip strength is a measure of muscular strength and is used to study age-related loss of physical capacity. In order to explore the biological mechanisms that influence hand grip strength variation, an epigenome-wide association study (EWAS) of hand grip strength in 672 middle-aged and elderly monozygotic twins (age 55–90 years) was performed, using both individual and twin pair level analyses, the latter controlling the influence of genetic variation. Moreover, as measurements of hand grip strength performed over 8 years were available in the elderly twins (age 73–90 at intake), a longitudinal EWAS was conducted for this subsample. No genome-wide significant CpG sites or pathways were found, however two of the suggestive top CpG sites were mapped to the COL6A1 and CACNA1B genes, known to be related to muscular dysfunction. By investigating genomic regions using the comb-p algorithm, several differentially methylated regions in regulatory domains were identified as significantly associated to hand grip strength, and pathway analyses of these regions revealed significant pathways related to the immune system, autoimmune disorders, including diabetes type 1 and viral myocarditis, as well as negative regulation of cell differentiation. The genes contributing to the immunological pathways were HLA-B, HLA-C, HLA-DMA, HLA-DPB1, MYH10, ERAP1 and IRF8, while the genes implicated in the negative regulation of cell differentiation were IRF8, CEBPD, ID2 and BRCA1. In conclusion, this exploratory study suggests hand grip strength to associate with differentially methylated regions enriched in immunological and cell differentiation pathways, and hence merits further investigations.Electronic supplementary materialThe online version of this article (10.1007/s10522-019-09818-1) contains supplementary material, which is available to authorized users.

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Cross‐sectional relations of whole‐blood miRNA expression levels and hand grip strength in a community sample

Cited by 13 publications

References 46 publications

MicroRNA Expression Profiles Identify Biomarker for Differentiating the Embolic Stroke from Thrombotic Stroke

MicroRNA Expression Profiles Identify Biomarker for Differentiating the Embolic Stroke from Thrombotic Stroke

Objective physical activity and physical performance in middle-aged and older adults

Epigenome-wide exploratory study of monozygotic twins suggests differentially methylated regions to associate with hand grip strength

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