A Plasma Proteomic Signature of Skeletal Muscle Mitochondrial Function

Area of Science:

• Biochemistry
• Physiology
• Gerontology

Background:

• Mitochondrial dysfunction is linked to aging, reduced physical function, and age-related diseases.
• Current measures of mitochondrial health lack accessibility and affordability.
• A non-invasive biomarker for mitochondrial health is needed.

Purpose of the Study:

• To identify a plasma proteomic signature correlating with skeletal muscle mitochondrial oxidative capacity.
• To establish an accessible measure of mitochondrial health.

Main Methods:

• Analyzed plasma protein concentrations in 165 adults using the SOMAscan assay.
• Assessed skeletal muscle maximal oxidative phosphorylation capacity via phosphorous magnetic resonance spectroscopy (assessed as post-exercise phosphocreatine recovery time constant, τ_PCr).
• Correlated protein concentrations with τ_PCr, adjusting for age, sex, and phosphocreatine depletion.

Main Results:

• Identified 87 plasma proteins significantly associated with skeletal muscle oxidative capacity (τ_PCr).
• Sixty proteins correlated positively with better mitochondrial function, while 27 correlated with poorer function.
• Enriched protein clusters involved in energy metabolism, proteostasis, oxidative stress response, and inflammation.

Conclusions:

• Plasma proteomic profiles can serve as a surrogate marker for skeletal muscle mitochondrial oxidative capacity.
• This discovery paves the way for accessible and affordable assessment of mitochondrial health.
• Further validation in independent cohorts and longitudinal studies is recommended.