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Exercise & healthspan
Research brief

Methylome and transcriptome signatures in aged rat soleus muscle of high- versus low-running-capacity lines

In soleus muscle of aged rats bred for high or low running capacity, the abstract reports broad baseline methylome remodeling, 322 differentially expressed genes and 72 methylome-transcriptome pairs; chronic voluntary running produced more differentially expressed genes in high-capacity muscle, while both lines converged on mitochondrial and oxidative metabolism. [1]

Automatic summary · not editorially reviewed

The key findings

  1. Soleus muscle from aged rats selectively bred for high or low running capacity (23–24 months) was profiled by methylation and RNA sequencing, with an age-comparable voluntary-running cohort also analyzed. [1]

  2. The abstract reports 7196 significant differentially methylated regions, 322 differentially expressed genes between the lines, and 72 region–gene pairs covering 53 unique genes. [1]

  3. Chronic voluntary running induced more differentially expressed genes in high- than low-capacity muscle, while both lines converged on mitochondrial and oxidative metabolism at pathway level. [1]

The source at a glance

Study type / format
Abstract of a preclinical animal study with molecular profiling and an exercise cohort
Population / context
Aged rats (23–24 months) selectively bred for high or low running capacity, plus an age-comparable voluntary-running cohort; soleus muscle.
Summary based on
Study abstract
Original publication
September 17, 2026

Aged rat soleus: high versus low running capacity

The abstract describes soleus muscle from aged rats selectively bred for high (HCR) or low (LCR) running capacity, aged 23–24 months. Muscle was profiled with reduced representation bisulfite sequencing for methylation and RNA sequencing for gene expression. An age-comparable voluntary-running cohort was also analyzed by RNA sequencing and selected protein profiling to assess exercise adaptation. The question was whether intrinsic aerobic-capacity differences in aged muscle have epigenomic and transcriptomic features and distinct exercise-related molecular responses.

Supporting source [1]

Baseline methylome, 322 genes and 72 paired regions

At baseline, the abstract reports 7196 significant differentially methylated regions, with a higher proportion of hypermethylated regions in HCR muscle. These regions were mainly at open-sea CpGs; gene-associated regions were predominantly intronic and exonic and showed context-dependent functional enrichment. RNA sequencing identified 322 differentially expressed genes between HCR and LCR muscle. Integration revealed 72 differentially methylated region–gene pairs covering 53 unique genes, mostly in open-sea, intronic and exonic regions. An exploratory analysis linked 63 regions to aerobic capacity.

Supporting source [1]

Running response and protein differences in both lines

Chronic voluntary running induced more differentially expressed genes in HCR than in LCR muscle, while pathway-level responses in both lines converged on mitochondrial and oxidative metabolism. Selected protein profiling showed mainly baseline LCR–HCR differences, with limited additional exercise-associated changes. The abstract concludes that intrinsic high aerobic capacity in aged skeletal muscle is associated with hypermethylation-enriched methylome remodeling, feature-dependent functional enrichment, distinct transcriptional signatures and oxidative-metabolic protein differences. It presents these as a multi-layer molecular framework and candidate regulatory regions for future functional validation.

Supporting source [1]

How to interpret this

This explainer is based only on the abstract; the full text was not reviewed. The abstract reports no sample sizes per group, no effect sizes or statistical details for most comparisons, and the aerobic-capacity analysis is described as exploratory. The findings are associations in a rat model, not evidence of human lifespan or health benefits, and the candidate regulatory regions require future functional validation.

Based on the study abstract; the full paper, tables and supplementary data were not reviewed.

Source & supporting passages

[1]
Methylome-transcriptome integration reveals molecular signatures of intrinsic aerobic capacity in aged skeletal muscle.

Zhou L, Mozaffaritabar S, Torma F, Koltai E, Kawamura T, Higuchi M, Zhong Z, Koch LG, Britton SL, Radák Z. · europepmc.org · September 17, 2026

Read the quoted passagesIn the language of the original source
  1. Finding 1 ↑

    Soleus muscle from aged selectively bred high-
  2. Finding 2 ↑

    Baseline RNA-seq identified 322 DEGs between HCR
  3. Finding 3 ↑

    Chronic voluntary running induced more DEGs in

AI-assisted summary with linked source passages. No independent editorial or clinical review.

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