Evidence map›Paper›PMID 37898813›Full record

ArticleSkeletal muscle2023

DNA methylation of insulin signaling pathways is associated with HOMA2-IR in primary myoblasts from older adults.

Mark A Burton, Emma S Garratt, Matthew O Hewitt, Hanan Y Sharkh, Elie Antoun, Leo D Westbury, Elaine M Dennison, Nicholas C Harvey, Cyrus Cooper, Julia L MacIsaac and 4 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Skeletal muscle, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.5field-weighted citation impact, top 32% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 3 citations in OpenAlex.

  1. Review
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 4 institutions in 2 countries.

Mark A Burton *Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK.
Emma S Garratt *Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK.
Matthew O HewittHuman Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK.
Hanan Y SharkhHuman Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK.
Elie AntounHuman Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK.
Leo D WestburyMRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, UK.
Elaine M DennisonNIHR Southampton Biomedical Research Centre, University of Southampton & University Hospital Southampton NHS Foundation Trust, Southampton, UK.
Nicholas C HarveyNIHR Southampton Biomedical Research Centre, University of Southampton & University Hospital Southampton NHS Foundation Trust, Southampton, UK.
Cyrus CooperNIHR Southampton Biomedical Research Centre, University of Southampton & University Hospital Southampton NHS Foundation Trust, Southampton, UK.
Julia L MacIsaacDepartment of Medical Genetics, Faculty of Medicine, Edwin S.H. Leong Healthy Aging Program, University of British Columbia, Vancouver, Canada.
Michael S KoborDepartment of Medical Genetics, Faculty of Medicine, Edwin S.H. Leong Healthy Aging Program, University of British Columbia, Vancouver, Canada.
Harnish P Patel *NIHR Southampton Biomedical Research Centre, University of Southampton & University Hospital Southampton NHS Foundation Trust, Southampton, UK.
Keith M Godfrey *Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK.
Karen A Lillycrop *Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK. kal@soton.ac.uk.ORCID 0000-0001-7350-5489
University Hospital Southampton NHS Foundation Trust · GBUniversity of Southampton · GBUniversity of British Columbia · CAMRC Lifecourse Epidemiology Unit · GB

Funding

Interdisciplinary Research Network on Early Adversity & Later Life ReversibilityU24AG047867 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GODFREY, KEITH, MCEWEN, BRUCE S. · 2014 to 2018
$954k
Biotechnology and Biological Sciences Research Council ES/M0099XMedical Research Council G0400491Medical Research Council G0601019Medical Research Council MC_PC_21000Medical Research Council MC_PC_21001Medical Research Council MC_PC_21003Medical Research Council MC_PC_21022Medical Research Council MC_U147585819Medical Research Council MC_U147585824Medical Research Council MC_U147585827Medical Research Council MC_UP_A620_1014Medical Research Council MC_UP_A620_1015Medical Research Council MC_UU_12011/1Medical Research Council MC_UU_12011/2NIA NIH HHS U24 AG047867Versus Arthritis 19583
6 · The paper itself

Abstract

backgroundWhile ageing is associated with increased insulin resistance (IR), the molecular mechanisms underlying increased IR in the muscle, the primary organ for glucose clearance, have yet to be elucidated in older individuals. As epigenetic processes are suggested to contribute to the development of ageing-associated diseases, we investigated whether differential DNA methylation was associated with IR in human primary muscle stem cells (myoblasts) from community-dwelling older individuals.

methodsWe measured DNA methylation (Infinium HumanMethylationEPIC BeadChip) in myoblast cultures from vastus lateralis biopsies (119 males/females, mean age 78.24 years) from the Hertfordshire Sarcopenia Study extension (HSSe) and examined differentially methylated cytosine phosphate guanine (CpG) sites (dmCpG), regions (DMRs) and gene pathways associated with HOMA2-IR, an index for the assessment of insulin resistance, and levels of glycated hemoglobin HbA1c.

resultsThirty-eight dmCpGs (false discovery rate (FDR) < 0.05) were associated with HOMA2-IR, with dmCpGs enriched in genes linked with JNK, AMPK and insulin signaling. The methylation signal associated with HOMA2-IR was attenuated after the addition of either BMI (6 dmCpGs), appendicular lean mass index (ALMi) (7 dmCpGs), grip strength (15 dmCpGs) or gait speed (23 dmCpGs) as covariates in the model. There were 8 DMRs (Stouffer < 0.05) associated with HOMA2-IR, including DMRs within T-box transcription factor (TBX1) and nuclear receptor subfamily-2 group F member-2 (NR2F2); the DMRs within TBX1 and NR2F2 remained associated with HOMA2-IR after adjustment for BMI, ALMi, grip strength or gait speed. Forty-nine dmCpGs and 21 DMRs were associated with HbA1c, with cg13451048, located within exoribonuclease family member 3 (ERI3) associated with both HOMA2-IR and HbA1c. HOMA2-IR and HbA1c were not associated with accelerated epigenetic ageing.

conclusionsThese findings suggest that insulin resistance is associated with differential DNA methylation in human primary myoblasts with both muscle mass and body composition making a significant contribution to the methylation changes associated with IR.

Indexed as

Insulin ResistanceAgedDNA MethylationFemaleGlycated HemoglobinHumansInsulinMaleMyoblastsSignal TransductionGlycated HemoglobinInsulinDNA methylationHOMA2-IRInsulin resistanceSkeletal muscle

Identifiers

PMID37898813
PMCPMC10612387
OpenAlexW4388002068

What Socratic holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.