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Mtc2.5
MOTS-c – Forschung
Überwiegend Mechanismus / Beobachtung
15 begutachtete Studien
Was die Evidenz sagt
Überwiegend Mechanismus / Beobachtung
Die meisten Studien zu MOTS-c sind mechanistisch oder beobachtend statt RCTs, die einen klinischen Effekt messen — betrachte die Ergebnisse als vorläufig.
Die meiste Evidenz stammt aus gemischt-qualitativen Meta-Analysen und randomisierten Studien, veröffentlicht 2015–2026 mit einer typischen Studiengröße von 435 Teilnehmenden.
Basierend auf 15 Studien · 1 Meta-Analyse · 1 RCT · 445 Teilnehmende insgesamt
Konfidenz
Mittlere Konfidenz
Nach Outcome
Longevity & agingEin aus Mitochondrien abgeleitetes Peptid mit trainingsimitierenden und metabolischen Effekten im Tiermodell sowie beobachtungsbasierten Assoziationen beim Menschen; keine interventionelle Evidenz beim Menschen. · Nicht belegt (keine interventionellen Humandaten)
Überwiegend Mechanismus / Beobachtung10 Studien
Glucose & metabolicVerbesserte Insulinsensitivität/Glukosestoffwechsel ausschließlich im Tiermodell; Humandaten sind beobachtungsbasiert, nicht interventionell. · Nicht belegt (keine interventionellen Humandaten)
Überwiegend Mechanismus / Beobachtung5 Studien
Exercise & physical performance
Überwiegend Mechanismus / Beobachtung3 Studien
Aktives Forschungsgebiet
7 Studien in den letzten 5 Jahren · Neueste Meta-Analyse: 2024
201520202026
1RCTn=10 · very small study2025
Einfach gesagt: Further research is needed to elucidate the underlying mechanisms and explore the therapeutic potential of heat stress and mitokines in mitigating muscle loss.
Elhusseiny R, Ihsan M, Labidi M, Alhammoud M, Mtibaa K, Nader N, Nasir N, Farooq A, Papakostas E, Olory B, Cruz F, D'Hooghe P, Racinais S, Deldicque L. · Medicine and science in sports and exercise (2025)
Results Although immobilization did not induce any effect on mitokine levels, repeated heat treatment upregulated the circulating MOTS-c ( P = 0.033) and downregulated the skeletal muscle FGF21 ( P = 0.027) levels.
Immobilization decreased muscle thickness ( P = 0.012, η2 = 0.32) and cross-sectional area ( P < 0.01, η2 = 0.75) of the gastrocnemius medialis.
Conclusions Our results indicate that repeated heat stress specifically modulates the levels of the mitokines MOTS-c and FGF21 in a manner that is comparable to, but not identical to, exercise.
Einfach gesagt: Therefore, further research, particularly controlled clinical trials and longitudinal studies, is needed to confirm these findings and evaluate MDP's potential as a therapeutic target in the prevention and management of metabolic diseases.
Ayubi N, Wibawa JC, Kurnaz M, Komaini A. · Physiology international (2026)
However, these findings should be interpreted with caution due to the limited number of studies and variations in study design, subject characteristics, and exercise protocols.
Conclusion Available evidence suggests that physical exercise has the potential to increase MDP levels, which may be associated with improved metabolic function, increased insulin sensitivity, and the efficiency of cellular energy metabolism.
However, current evidence is limited, particularly in human studies.
Einfach gesagt: Its primary target organ appears to be the skeletal muscle, and its cellular actions inhibit the folate cycle and its tethered de novo purine biosynthesis, leading to AMPK activation.
Lee C, Zeng J, Drew BG, Sallam T, Martin-Montalvo A, Wan J. · Cell Metab (2015)
Discovery paper: identifies MOTS-c, a 16-amino-acid peptide encoded within the mitochondrial 12S rRNA, that regulates insulin sensitivity and metabolic homeostasis
Cellular action is inhibition of the folate cycle and de novo purine biosynthesis, leading to AMPK activation, with skeletal muscle as the primary target
MOTS-c treatment in mice prevented age-dependent and high-fat-diet-induced insulin resistance and diet-induced obesity
Einfach gesagt: Mitochondrial-encoded MOTS-c can significantly enhance physical performance in young (2 mo.), middle-age (12 mo.), and old (22 mo.) mice... In humans, exercise induces endogenous MOTS-c expression in skeletal muscle and in circulation.
Reynolds JC, Lai RW, Woodhead JST, Joly JH, Mitchell CJ, Cameron-Smith D. · Nat Commun (2021)
In mice, MOTS-c treatment enhanced physical performance across young, middle-aged and old animals, and late-life intermittent dosing (3×/week) increased physical capacity and healthspan
MOTS-c regulated nuclear genes related to metabolism and proteostasis and modulated skeletal-muscle metabolism and myoblast stress adaptation
Human component is observational: exercise induced endogenous MOTS-c in skeletal muscle and circulation — not an interventional trial of administered MOTS-c
Einfach gesagt: MOTS-c... translocates to the nucleus and regulates nuclear gene expression following metabolic stress in a 5'-adenosine monophosphate-activated protein kinase (AMPK)-dependent manner.
Kim KH, Son JM, Benayoun BA, Lee C. · Cell Metab (2018)
Mechanistic cell study showing MOTS-c translocates to the nucleus and regulates nuclear gene expression in an AMPK-dependent manner under metabolic stress
Under glucose restriction, MOTS-c regulated genes with antioxidant response elements (ARE) and interacted with the stress transcription factor NRF2 (NFE2L2)
Frames a bi-genomic 'mitonuclear' communication mechanism — a mitochondrial-encoded factor controlling the nuclear genome
Einfach gesagt: MOTS-c may act as an inhibitor of VC by activating the AMPK signaling pathway and suppressing the expression of the AT-1 and ET-B receptors.
Wei M, Gan L, Liu Z, Liu L, Chang JR, Yin DC. · Cardiorenal Med (2020)
Rat vitamin-D3/nicotine vascular-calcification model; MOTS-c injected at 5 mg/kg/day for 4 weeks
MOTS-c significantly attenuated vascular calcification and secondary myocardial remodeling on echocardiography and histology
Mechanistically raised phosphorylated AMPK and lowered angiotensin-II type-1 (AT-1) and endothelin-B (ET-B) receptor expression
Einfach gesagt: MOTS-c treatment significantly alleviated bone loss... MOTS-c increased phosphorylated AMPK levels, and compound C, an AMPK inhibitor, could partially abrogate the effects of the MOTS-c on osteoclastogenesis.
Ming W, Lu G, Xin S, Huanyu L, Yinghao J, Xiaoying L. · Biochem Biophys Res Commun (2016)
Mouse ovariectomy osteoporosis model; MOTS-c injected at 5 mg/kg/day for 12 weeks
MOTS-c significantly reduced bone loss on micro-CT and inhibited RANKL-induced osteoclast differentiation
Effect depended on AMPK: MOTS-c raised phosphorylated AMPK and the AMPK inhibitor compound C partially abrogated the benefit
Einfach gesagt: Circulating MOTS-c reduced with age, but older (70-81 y) and middle-aged (45-55 y) men had ~1.5-fold higher skeletal muscle MOTS-c expression than young (18-30 y).
D'Souza RF, Woodhead JST, Hedges CP, Zeng N, Wan J, Kumagai H. · Aging (Albany NY) (2020)
Human observational study of plasma and skeletal-muscle MOTS-c across young, middle-aged and older healthy men
Circulating MOTS-c declined with age, while muscle MOTS-c expression was higher in older/middle-aged men and tracked slow-type myofiber markers
In older men, muscle MOTS-c was associated with better muscle quality (leg-press load relative to thigh cross-sectional area)
Einfach gesagt: MOTS-c has been used less frequently in disease treatment, and no effective method of applying MOTS-c in the clinic has been developed.
Zheng Y, Wei Z, Wang T. · Front Endocrinol (Lausanne) (2023)
Review of MOTS-c biology and its proposed roles in aging, cardiovascular disease, insulin resistance and inflammation
Describes nuclear translocation under metabolic stress, improved skeletal-muscle glucose metabolism, and an age-related decline in plasma levels
Explicitly states no effective clinical application of MOTS-c has been developed — underscoring the lack of human therapeutic evidence
Einfach gesagt: Among MDPs, mitochondrial ORF of the 12S rRNA type-c (MOTS-c) is the most associated with exercise... Systemic MOTS-c administration increases exercise performance by boosting skeletal muscle stress responses.
Yoon TK, Lee CH, Kwon O, Kim MS. · Diabetes Metab J (2022)
Review of MOTS-c within exercise-related mitohormesis (the beneficial response to low-level mitochondrial stress)
Summarizes that MOTS-c rises in skeletal muscle, circulation and hypothalamus with exercise, and that exogenous MOTS-c boosts performance and adipose thermogenesis in animal studies
Frames MOTS-c as a mediator of some salutary metabolic effects of exercise
Einfach gesagt: Increased β-amyloid or low MOTS-c are additive predictors to high on-clopidogrel platelet reactivity for adverse outcome in diabetics with CAD during 2-years follow-up.
Ikonomidis I, Katogiannis K, Kyriakou E, Taichert M, Katsimaglis G, Tsoumani M. · J Thromb Thrombolysis (2020)
Prospective observational cohort of 121 type 2 diabetics after coronary revascularization (plus a 90-patient external validation cohort); MOTS-c measured by blood assay
Low MOTS-c (< 167 ng/ml) independently predicted major adverse cardiac events over 2 years (relative risk 3.8), additive to high on-clopidogrel platelet reactivity
An association/prognostic-marker study of endogenous circulating MOTS-c, not an interventional trial of administered MOTS-c
Einfach gesagt: This is the first study to show increased lipid enhanced circulating MOTS-c whilst insulin attenuated the MOTS-c response in human... eight weeks of moderate exercise training did not show any changes in circulating MOTS-c levels.
Ramanjaneya M, Jerobin J, Bettahi I, Bensila M, Aye M, Siveen KS. · Clin Endocrinol (Oxf) (2019)
Human observational/physiology study in PCOS and healthy subjects using intralipid infusion + hyperinsulinaemic-euglycaemic clamp, with plasma MOTS-c measured by ELISA
Intralipid significantly raised plasma MOTS-c (to ~232% basal in controls, ~349% in PCOS); insulin infusion blunted the lipid-induced rise
Notably, eight weeks of moderate exercise training did NOT change circulating MOTS-c in either group — a null human finding
Einfach gesagt: We suggest that the m.1382A>C polymorphism located in the MOTS-c encoding mtDNA, which is specific for the Northeast Asian population, may be among the putative biological mechanisms explaining the high longevity of Japanese people.
Fuku N, Pareja-Galeano H, Zempo H, Alis R, Arai Y, Lucia A. · Aging Cell (2015)
Hypothesis/perspective linking a MOTS-c-encoding mtDNA polymorphism (m.1382A>C) to exceptional longevity in Northeast Asian populations
Frames circulating MOTS-c decline and genetic variation as putative aging mechanisms — explicitly noting more research is needed
An association/hypothesis paper, not interventional evidence