InterventionsAnimalsPreprint

Inhibiting miR-128-3p restores muscle mass and function in aged mice

The microRNA inhibitor also improved cardiac outcomes after infarction and reduced pathology in mouse and pig models of muscular dystrophy.

Figure 1. SNPs in the miR-128 loci are associated with muscle and pulmonary function in humans and anti-miR-128 improves muscle function and transcriptional programs in aged mice. — Figure 1. SNPs in the miR-128 loci are associated with muscle and pulmonary function in humans and anti-miR-128 improves muscle function and transcriptional programs in…SNPs in the miR-128 loci are associated with muscle and pulmonary function in humans and anti-miR-128 improves muscle function and transcriptional programs in aged mice.Boldridge et al.

bioRxiv3 Oct 2026, 00:14 BST

In aged mice, inhibiting the microRNA miR-128-3p with antisense oligonucleotides restored muscle mass and function, according to a recent preprint. The researchers targeted miR-128-3p because its genomic locus associates with variation in human grip strength, pulmonary function, and cardiometabolic traits. Beyond restoring aged muscle, miR-128-3p inhibition improved cardiac function and limited adverse remodeling after myocardial infarction in mice. It also ameliorated skeletal and cardiac muscle pathology in mouse and pig models of Duchenne muscular dystrophy. Across these settings, blocking miR-128-3p activated mitochondrial gene programs and suppressed inflammatory and fibrotic signaling, resembling patterns produced by established longevity interventions.

Why it matters

These findings identify miR-128-3p as a regulator of a conserved striated muscle aging program involving mitochondrial dysfunction and inflammation. The results demonstrate that aging-related functional declines in muscle can be pharmacologically reversed in animal models.

Caveats

The work is reported in a preprint and has not yet completed peer review. While the locus is linked to human traits, therapeutic interventions were evaluated only in mouse and pig models.