SKELETAL MUSCLE TRANSCRIPTIONAL AND REGULATORY SIGNALING ADAPTATIONS TO HIGH-INTENSITY INTERVAL TRAINING VERSUS MODERATE-INTENSITY CONTINUOUS TRAINING: A SYSTEMATIC REVIEW

Abstract

The p53 (tumor protein 53), mitochondrial transcription factor A (TFAM) and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) are an integrated network of transcriptional regulators of mitochondrial biogenesis in skeletal muscle. The question of whether high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) produce similar activation of these upstream regulatory pathways in humans is not well understood. A recent meta-regression has synthesized training impacts on mitochondrial content markers but has not considered regulatory signaling particularly. Our search was a systematic review of randomized and quasi-randomized comparative trials on healthy adults to examine the effects of HIIT compared with MICT on transcriptional and regulatory comparative signatures of mitochondrial biogenesis on human skeletal muscle. A structured search strategy in PubMed/MEDLINE, Cochrane CENTRAL, and Embase up to April 2026 was used, including interval training, skeletal muscle, and regulatory signaling outcomes. Two reviewers individually screened 298 deduplicated records, evaluated full texts, and elicited data. Cochrane RoB 2 was used as the instrument to evaluate the risk of bias. There were 4 trials (n=81 good individuals) that passed all the eligibility criteria. PGC-1α was measured in 5 HIIT-versus-comparator comparisons, p53 and TFAM were each measured in 2 comparisons in a single 3-arm trial. HIIT and MICT enhanced the expression of PGC-1α in three of four trials, in which training duration was at least six weeks, and there was no clear difference in effectiveness of either modality. Only the all-out sprint interval training arm activated p53 signaling and PGC-1α, in contrast to work-matched HIIT and continuous training, in a four-week intervention. There was no change of TFAM with any modality. The evidence base is small and does not permit quantitative pooling and additional direct head-to-head comparisons have to be conducted.