Cardiolipin loss drives muscle fiber shifts during aging via a nuclear receptor
Restoring cardiolipin synthesis in knockout mice reversed muscle atrophy and prevented premature death.
Nature aging · Finger F et al. · Paper published 29 Sep 2026
In mice and human skeletal muscle, the loss of the mitochondrial membrane lipid cardiolipin links organelle dysfunction to aging-related fiber adaptations. Researchers depleted cardiolipin in young mice by deleting muscle cardiolipin synthase 1. This deletion reproduced key hallmarks of aging, including a transition from glycolytic to oxidative fibers. The shift was mediated by mitochondria-to-nucleus signaling through estrogen-related receptor γ, which enhanced reactive oxygen species-sensitive glucose uptake and rerouted glycolysis to maintain antioxidant defenses. Restoring cardiolipin synthase 1 expression in adult knockout mice replenished cardiolipin, initiated the reversal of muscle atrophy, and fully prevented premature mortality.
Why it matters
The study identifies a lipid-driven signaling pathway that explains why aging muscle paradoxically shifts toward mitochondria-rich fibers despite overall mitochondrial decline.
Caveats
The causal mechanisms and genetic rescue interventions were demonstrated primarily in mice, meaning translation to human muscle aging remains to be confirmed.
Written from the paper’s abstract, and every claim checked against it before publishing. Read the paper for the full methods and data.
The paper
Mitochondrial membrane lipid cardiolipin controls fiber-type adaptations in aging muscle via estrogen-related receptor γ
Finger F, Frost M, Watanabe S et al.
Nature aging · 29 Sep 2026 · Peer-reviewed
- Relevance
- Core geroscience
- News value
- Important
- Evidence
- Animals
- Status
- Peer-reviewed
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