Cardiolipin loss in aging muscle linked to fiber-type shift via ERRγ in mice and human tissue
In aging mouse and human skeletal muscle, the abstract links falling cardiolipin levels to a shift toward mitochondria-rich oxidative fibers, mediated by mitochondria-to-nucleus signaling through estrogen-related receptor γ. [1]
Automatic summary · not editorially reviewed
The key findings
The abstract reports that cardiolipin synthesis causally links mitochondrial dysfunction to fiber-type adaptations in aging mouse and human skeletal muscle. [1]
Inducible tissue-specific Crls1 deletion in young mice reproduced aging hallmarks, including the shift from glycolytic to oxidative fibers, mediated by estrogen-related receptor γ. [1]
Restoring Crls1 expression in adult Crls1 knockout mice reestablished cardiolipin levels, began reversing muscle atrophy and fully rescued premature mortality. [1]
The source at a glance
- Study type / format
- Abstract of a preclinical and tissue-based mechanistic study
- Population / context
- Aging mouse and human skeletal muscle; young and adult Crls1 knockout mice.
- Summary based on
- Study abstract
- Original publication
- September 29, 2026
Aging muscle paradox in mice and humans
The abstract describes a paradox: aging brings both a decline in skeletal muscle mitochondrial function and a shift toward fibers rich in mitochondria. The biological reason and mechanism were largely unknown. The authors report that synthesis of the mitochondrial membrane lipid cardiolipin causally links mitochondrial dysfunction to fiber-type adaptations in aging mouse and human skeletal muscle.
Supporting source [1]
Crls1 deletion in young mice mimics aging shift
To mimic the aging decline of muscle cardiolipin in young mice, the researchers used inducible, tissue-specific deletion of cardiolipin synthase 1 (Crls1). This reproduced key aging hallmarks, including the shift from glycolytic to oxidative fibers. The shift is mediated by mitochondria-to-nucleus signaling through the nuclear receptor estrogen-related receptor γ, which promotes reactive oxygen species-sensitive glucose uptake and enhanced glycolytic rerouting to sustain antioxidant defenses.
Supporting source [1]
Restoring Crls1 in adult knockout mice
Restoring Crls1 expression in adult Crls1 knockout mice reestablished cardiolipin levels, began reversing muscle atrophy and fully rescued premature mortality, according to the abstract. The authors say the findings show how changes in a mitochondrial membrane lipid cell autonomously orchestrate fiber-type adaptations in aging and myopathies. These are abstract-level results in mice and human tissue; the full text was not reviewed, and the abstract does not report sample sizes, follow-up or effect sizes.
Supporting source [1]
How to interpret this
Abstract only; the full text was not reviewed. The abstract does not report sample sizes, follow-up, effect sizes or whether the human data are observational. Mouse deletion and rescue results do not establish human lifespan or clinical benefits.
Based on the study abstract; the full paper, tables and supplementary data were not reviewed.
Source & supporting passages
Finger F, Frost M, Watanabe S, Ma T, Kang T, Biswas D, Zapata-Perez R, Anton V, Dollet L, Markussen LK, Senoo N, Karavaeva I, Basse AL, Dmytriyeva O, TeSlaa T, Havelund JF, Ehrlich AM, Moreno-Torres M, Yonamine CY, Andersen NR, Blom I, Garcia-Carrizo F, Siripoksup P, Asping M, Nielsen TS, Nygård M, Klein AB, Tvardovskiy A, Nicolaisen TS, Durantez-Fernández C, Qvortrup K, Prats C, Rabinowitz JD, Clemmensen C, Sylow L, Zierath JR, Treebak JT, Schulz TJ, Grevengoed TJ, Claypool SM, Prudent J, Wüst RCI, Mandrup S, Houtkooper RH, Sakamoto K, Færgeman NJ, Larsen MR, Funai K, Larsen S, Gerhart-Hines Z. · europepmc.org · September 29, 2026