| Zhang 2026 Antioxidants (Basel) Endogenous MOTS-c measured | Human obs. Healthy young males stratified as elite track and field athletes, recreationally active and sedentary; serum MOTS-c and fitness testing | Measured progressively higher serum MOTS-c from sedentary to recreationally active to elite athlete groups of young males. Reported strong positive correlations of serum MOTS-c with peak oxygen uptake, superoxide dismutase, back muscle endurance and post-fatigue force, a strong inverse correlation with post-exercise malondialdehyde, and no significant correlation with handgrip strength. | Very small groups of 10 young males each; cross-sectional design precludes causal inference; multiple strong correlations in a small sample risk overfitting. | Evidence tier B |
| Horwath 2026 Exp Physiol Endogenous MOTS-c measured | Human obs. Adults with cerebral palsy using running frames and typically developing adults and adolescents; plasma MDPs before and after endurance exercise | Measured plasma MOTS-c, humanin and SHMOOSE in adults with cerebral palsy and typically developing participants and found comparable basal levels despite lower muscle mass and peak oxygen uptake in the cerebral palsy group. Reported no or only modest changes in circulating MDPs after an acute endurance exercise bout, with no differences between groups. | Small group sizes not reported in the abstract; single post-exercise sampling point; in-house ELISA without external validation and heterogeneous exercise modes between groups. | Evidence tier B |
| Elhusseiny 2025 Med Sci Sports Exerc Endogenous MOTS-c measured | Human obs. Physically active young adult men undergoing unilateral ankle immobilization after supervised training | Measured circulating and skeletal muscle mitokine levels in physically active men during ankle immobilization and reported that immobilization itself did not change mitokine levels. Found higher circulating MOTS-c and lower skeletal muscle FGF21 in the repeated heat-treatment group than in the sham group, while immobilization decreased gastrocnemius medialis muscle thickness and cross-sectional area in these participants. | Small sample of 19 men with roughly nine or ten per arm; men only and physically active volunteers, limiting generalisability; MOTS-c was a secondary mitokine outcome and the comparison with exercise was not directly tested. | Evidence tier B |
| Feng 2025 Free Radic Biol Med Endogenous MOTS-c measured | Human obs. Marathon runners and sedentary subjects, and mice undergoing long-term endurance training | Measured serum MOTS-c levels that were closely associated with aerobic exercise capacity in marathon runners and sedentary subjects. In mice, reported higher serum MOTS-c and greater skeletal muscle mitochondrial respiration after long-term endurance training than in sedentary mice, alongside AMPK/PGC-1α activation. | Human sample sizes are not reported and the human comparison is cross-sectional, so training and selection effects cannot be separated; the mouse mechanism was not tested in people. | Evidence tier B |
| Jia 2024 Theranostics Several | Human obs. Human participants after moderate-intensity or high-intensity eccentric exercise, TRIM72 knockout mice, and cultured muscle and endothelial cells | Measured MOTS-c levels in human participants that correlated positively with mitochondrial abundance and with TRIM72, with greater MOTS-c secretion after moderate-intensity than after high-intensity eccentric exercise. In cells and mice, MOTS-c was reported to promote TRIM72 trafficking to damaged membrane and to interact with phosphatidylinositol (4,5) bisphosphate, while having little membrane-repair effect on its own. | Human sample size and characteristics are not reported and the human data are correlative; animal work relies on a single knockout line; the mix of models makes attribution of each finding difficult. | Evidence tier B |
| Domin 2023 Int J Mol Sci Endogenous MOTS-c measured | Human obs. Physically active healthy volunteers undergoing countermovement jump tests, cardiopulmonary exercise testing and bioelectrical impedance analysis | Measured resting serum MOTS-c concentration and related it to countermovement jump performance, cardiopulmonary exercise test results and body composition in physically active healthy adults. Reported that higher serum MOTS-c correlated positively with average power and with average and maximal jump force and with overall and leg muscle mass, but showed no correlation with body fat percentage or with peak oxygen uptake. | Small preliminary sample of 20 volunteers with a strong male predominance; cross-sectional correlational design with a single resting MOTS-c measurement and no control group; the authors describe it as preliminary and requiring replication. | Evidence tier B |
| Alser 2022 Rev Cardiovasc Med Several | Human obs. Serum MOTS-c and humanin in professional endurance athletes and non-athlete controls, measured by ELISA | Measured serum MOTS-c and humanin by ELISA and reported lower MOTS-c and higher humanin in professional athletes than in sedentary controls. Reported that within the athlete groups humanin was lower in high endurance than in low/moderate endurance athletes of the same sex and age group, that MOTS-c did not differ between those subgroups, and that the two peptides were strongly correlated in athletes but not in controls. | Described by the authors as pilot data; cross-sectional single-timepoint sampling with controls not matched for body composition or diet; unequal and small subgroups, particularly the high endurance group; training load characterised only by broad endurance category. | Evidence tier B |
| Kumagai 2022 Biochim Biophys Acta Gen Subj MT-RNR1 / K14Q variant | Human obs. Japanese adults genotyped for m.1382A>C with muscle fibre composition and strength testing, athlete and control allele-frequency groups, and young male mice given a MOTS-c neutralising antibody | Reported that carriers of the C allele of the East Asian-specific m.1382A>C variant, which produces MOTS-c K14Q, had a higher proportion of MHC-IIx fibres, and that men with the C allele had higher peak leg flexion and extension torque. C-allele frequency was higher in sprint and power athletes than controls and lowest in endurance athletes, and mice given a MOTS-c neutralising antibody showed higher MHC-fast expression. | Observational genetic associations in a single East Asian population with modest subgroup sizes, strength measured only in men, and the animal arm uses antibody neutralisation in young male mice as an indirect mimic of the variant. | Evidence tier B |
| Dieli-Conwright 2021 Sci Rep Endogenous MOTS-c measured | Human obs. Hispanic and non-Hispanic White breast cancer survivors randomised to an aerobic and resistance exercise programme or standard care | Measured fasting plasma MOTS-c in breast cancer survivors over a 16-week aerobic and resistance exercise intervention and found higher post-intervention levels than at baseline and than usual care among non-Hispanic White survivors, but not among Hispanic survivors. Post-intervention MOTS-c levels in non-Hispanic White survivors were associated with lower fat mass, body weight, HOMA-IR and C-reactive protein and higher lean mass. | Secondary analysis of a trial not designed for this outcome, small ethnic subgroups with baseline differences in age, adiposity and cancer stage, women only, and MOTS-c measured with an in-house ELISA. | Evidence tier B |
| von 2021 J Appl Physiol (1985) Endogenous MOTS-c measured | Human obs. Healthy participants randomised to acute endurance cycling, acute resistance exercise or a non-exercising control condition | Measured circulating mitochondrial-derived peptides before and after acute exercise in healthy adults and found that plasma humanin rose significantly after endurance but not resistance exercise, while MOTS-c showed only a trend towards an increase after endurance exercise. Resting MOTS-c correlated with humanin levels and age but not with fitness measures. | Small groups of ten participants each, single acute exercise bouts with short follow-up sampling, and MOTS-c changes that did not reach significance; participant sex distribution is not stated in the abstract. | Evidence tier B |