High-intensity interval exercise increases humanin, a mitochondrial encoded peptide, in the plasma and muscle of men.

Humanin, a small regulatory peptide encoded within the 16S ribosomal RNA gene (MT-RNR2) of the mitochondrial genome, has cellular cyto- and metabolo-protective properties similar to that of aerobic exercise training. Here we investigated whether acute high-intensity interval exercise or short-term high-intensity interval training (HIIT) impacted skeletal muscle and plasma humanin levels. Vastus lateralis muscle biopsies and plasma samples were collected from young healthy untrained men (n=10, 24.5+/-3.7 y) before, immediately following, and 4 h following the completion of 10 x 60 s cycle ergometer bouts at VO2peak power output (untrained). Resting and post-exercise sampling was also performed after six HIIT sessions (trained) completed over 2 weeks. Humanin protein abundance in muscle and plasma were increased following an acute high-intensity exercise bout. HIIT trended (p=0.063) to lower absolute humanin plasma levels, without effecting the response in muscle or plasma to acute exercise. A similar response in the plasma was observed for the small humanin-like peptide 6 (SHLP6), but not SHLP2, indicating selective regulation of peptides encoded by MT-RNR2 gene. There was a weak positive correlation between muscle and plasma humanin levels, and contraction of isolated mouse EDL muscle increased humanin levels approximately 4-fold. The increase in muscle humanin levels with acute exercise was not associated with MT-RNR2 mRNA or humanin mRNA levels (which decreased following acute exercise). Overall, these results suggest that humanin is an exercise sensitive mitochondrial peptide and acute exercise-induced humanin responses in muscle are non-transcriptionally regulated and may partially contribute to the observed increase in plasma concentrations.