Circular RNAs in skeletal muscle aging and sarcopenia: a critical review of evidence
This critical review sorts circular RNA evidence on skeletal muscle aging and sarcopenia into four levels, from discovery to functional intervention, and finds human biomarker validation still insufficient. [1]
Automatic summary · not editorially reviewed
The key findings
The review applies a four-level framework: discovery, mechanistic support, in vivo causality and functional intervention. [1]
circSnd1 and circDdb1 currently provide the strongest combination of functional preclinical evidence and association with aged human skeletal muscle. [1]
Clinical validation of a circulating circular RNA biomarker for sarcopenia remains insufficient. [1]
The source at a glance
- Study type / format
- Critical review (abstract)
- Population / context
- Skeletal muscle aging and sarcopenia, including aged human skeletal muscle and human blood or serum-vesicle samples
- Summary based on
- Study abstract
- Original publication
- October 3, 2026
Review scope: muscle aging and sarcopenia evidence levels
The review organizes literature on skeletal muscle aging and sarcopenia, which can follow interacting defects in protein balance, mitochondrial quality control, inflammatory signaling, nerve-muscle integrity, regeneration and mechanical-metabolic plasticity. It applies a four-level framework: discovery, mechanistic support, in vivo causality and functional intervention. Human linkage, species, treatment timing, site of action and whether a circular RNA is natural or engineered are assessed separately. The authors argue the field should prioritize rigorous validation over more descriptive cataloging.
Supporting source [1]
Strongest preclinical candidates: circSnd1 and circDdb1
According to the review, circSnd1 and circDdb1 currently offer the strongest combination of functional preclinical evidence and association with aged human skeletal muscle. circFUT10, circBBS9, circNEB and circGLIS3 cover less mature areas: regeneration, discovery, histology or muscle quality. Studies in non-aging atrophy, including circTmeff1 and engineered circmiR-29b, test whether proposed mechanisms stay active under defined catabolic stress. These are preclinical and model-based findings, not demonstrated human benefits.
Supporting source [1]
Human biomarker and therapy readiness remain limited
Human blood and serum-vesicle studies show discovery-level associations with strength or mobility, but clinical validation of a circulating circular RNA biomarker for sarcopenia remains insufficient. Therapeutic development is constrained by quantitative target credibility, systemic exposure of skeletal muscle, post-onset functional efficacy in aged organisms, safety, reversibility and independent replication. The abstract does not report sample sizes, follow-up or effect estimates.
Supporting source [1]
How to interpret this
Abstract only; the full text was not reviewed. No sample sizes, follow-up or effect estimates are reported, and most cited evidence is preclinical or discovery-level.
Based on the study abstract; the full paper, tables and supplementary data were not reviewed.
Source & supporting passages
Ngo THP, Lee W. · europepmc.org · October 3, 2026