Skeletal Muscle mRNA Splicing Variants Association With Four Different Fitness and Energetic Measures in the GESTALT Study
2025

Skeletal Muscle mRNA Splicing Variants and Fitness Measures

Sample size: 82 publication 10 minutes Evidence: moderate

Author Information

Author(s): Donega Stefano, Banskota Nirad, Gupta Esha, Gonzalez‐Freire Marta, Moore Ann Zenobia, Ubaida‐Mohien Ceereena, Munk Rachel, Zukley Linda, Piao Yulan, Bergeron Chris, Bergeron Jan, Bektas Arsun, Zampino Marta, Stagg Carole, Indig Fred, Hartnell Lisa M., Kaileh Mary, Fishbein Kenneth, Spencer Richard G., Gorospe Myriam, De Supriyo, Egan Josephine M., Sen Ranjan, Ferrucci Luigi

Primary Institution: National Institute on Aging, NIH

Hypothesis

We explored the association of human skeletal muscle transcriptomic with four measures of energetics and mitochondria oxidative capacity in healthy individuals.

Conclusion

A consistent mitochondrial signature emerged across all energetic measures, with alternative splicing enhanced in older, low fitness participants.

Supporting Evidence

  • Physical activity is essential for maintaining muscle mitochondrial function and aerobic capacity.
  • Individuals who engage in regular physical activity exhibit higher levels of mitochondrial proteins.
  • Octogenarian master athletes have higher muscle mitochondrial protein content compared to non-athlete controls.
  • Alternative splicing was enhanced in older, low fitness participants.

Takeaway

This study looked at how muscle genes change with different levels of fitness and age, finding that older people with lower fitness have more changes in their muscle genes.

Methodology

RNA sequencing of vastus lateralis muscle biopsies from participants was used to explore gene and splicing variant expression profiles.

Potential Biases

Self-reported physical activity measures may introduce substantial measurement error.

Limitations

The cross-sectional nature of the study cannot establish direct causal pathways between gene expression changes and the assessed energetic variables.

Participant Demographics

82 participants (50 men and 32 women), aged 22–89 years, free of major diseases.

Statistical Information

P-Value

p<0.01

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1002/jcsm.13603

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