Table 1.
Defining exercise intensities.
Table 2.
Study inclusion and exclusion criteria.
Table 3.
Summary of Included Studies.
Fig 1.
The selection process for studies included in the systematic review and meta-analysis detailing the number of records identified, screened, and assessed for eligibility, as well as those included in the final synthesis.
Table 4.
Summary of GRADE assessment for the quality of evidence across outcomes.
Fig 2.
Forest plots of meta-analyses for markers relating to mitochondrial biogenesis.
Effect of moderate intensity continuous training on: (A) Mitochondrial Volume Density, (B) Citrate Synthase Activity, (C) VO2 max, D) Protein Content of MFN2, E) PGC-1α, (F) TFAM (G) DRP1. Positive values favor an increase at post-training, and negative values favor decrease/no change at post-training. Effect sizes are expressed as standardized mean differences (SMD) with 95% confidence internals. Heterogeneity was assessed using the I2 statistic. a* young cohort, b* older cohort.
Fig 3.
Mitochondrial biogenesis and dynamics in human skeletal muscle in response to exercise.
Endurance type exercise increases expression of PPARGC1A (PGC-1α) which leads to an elevated level of PGC-1α. This coactivator interacts with transcription factors NRF1 and NRF2 promoting expression of TFAM, a protein integral for the initiation of mitochondrial biogenesis. TFAM is synthesized in the cytosol and imported into the mitochondrial matrix via TOM (Translocase of the Outer Membrane) and TIM (Translocase of the Inner membrane) complexes. Inside the mitochondria, TFAM binds to mtDNA to regulate replication and transcription. Mitochondrial morphology is maintained through dynamic remodeling: fusion is mediated by MFN1/MFN2 (outer membrane) and OPA1 (inner membrane), while fission is directed by the cytosolic protein DRP1 is recruited to the mitochondrial surface where is assembles into a ring-like structure, constricting and dividing the organelle into two distinct mitochondria. Together, these pathways ensure mitochondrial quality and adaptability to the energetic demands imposed by exercise in skeletal muscle cells. Figure generated in BioRender.com [68].