Kulkarni · Aging 2020 · randomized controlled trial · n=47 older adults (plus young reference cohort)

Metformin alters skeletal muscle transcriptome adaptations to resistance training in older adults.

Cited 41 times in the scientific literature.

Level 2 - randomized trial

Randomized controlled trial transcriptomic analysis

PubMed 33071237 · doi:10.18632/aging.104096 · record verified 2026-08-28

What was done

Analyzed skeletal muscle transcriptomes from 47 older adults who completed a 14-week randomized controlled trial comparing progressive resistance exercise training plus metformin (metPRT, n = 23) against resistance training plus placebo (plaPRT, n = 24). Baseline biopsy gene profiles were also compared against resting muscle biopsies from a young volunteer reference cohort.

What was found

The abstract reports qualitative pathway directions without specific numerical metrics, fold changes, or p-values. Resistance training upregulated extracellular matrix remodeling pathways and downregulated RNA processing pathways in both groups, though metformin reduced the number of differentially expressed genes in these pathways relative to placebo. Genes uniquely altered in the metPRT group regulated aging-related pathways, including cellular senescence and autophagy. Baseline differences between older adults and young volunteers were reduced after resistance training in the placebo arm and were reduced further in the metformin arm.

Why it matters

These findings suggest that while metformin blunts specific transcriptional cascades tied to muscle hypertrophy during resistance training, it simultaneously modifies distinct anti-aging molecular pathways such as autophagy and senescence in aging muscle.

Limits

The abstract provides no effect sizes, gene counts, or statistical significance metrics. The study is limited by a modest sample size (n = 47 older adults), and transcriptomic changes were not directly tied to long-term functional or clinical outcomes within the abstract.

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