Age was associated with reduced accessibility of gene-regulatory DNA in 287 human muscle biopsies

Age was associated with reduced accessibility of gene-regulatory DNA in 287 human muscle biopsies

Across 467 126 cell nuclei, the authors compared RNA-based gene activity with DNA accessibility, which indicates whether regulatory proteins can reach a given site. In three muscle fiber types, aging was associated more often with the closing than the opening of regulatory DNA.

On August 24, 2026, the authors published a preprint, a preliminary report that has not undergone independent peer review. They reanalyzed data from 287 frozen human muscle biopsies collected in 2023 to examine how age affects regulation within muscle fibers themselves.

For each sample, the researchers compared two measurements. RNA indicates which genes the cell is transcribing at the time of measurement. Chromatin accessibility, which measures how exposed a DNA region is within the nucleus, indicates whether regulatory proteins can reach it. Across the three fiber types, 68 to 72% of the regions whose accessibility changed with age became less accessible. Type 2a fibers contained 4 061 such regions.

Active enhancers were especially likely to close. These DNA regions help activate genes and can sometimes be located far from them. Sites where gene transcription begins were less common among the regions that closed. The RNA measurements did not fully reproduce this pattern. The new analysis identifies changes in access to regulatory regions that may not be reflected in current gene transcription.

The regions that closed were enriched for motifs, which are short DNA sequences that proteins recognize as binding sites. These included motifs for steroid hormone receptors, including the glucocorticoid and androgen receptors. The authors propose testing whether reduced accessibility at these sites lowers the sensitivity of muscle fibers to hormonal signals that support muscle maintenance and repair.