Latest studies
Every paper our editors flag with a plain-language note and an evidence rating. Filter by evidence, species, or design to find what actually applies to you.
- Study · MOTS-cWeak / none
MOTS-c attenuates hyperoxia-induced neonatal cardiac injury by inhibiting oxeiptosis via maintaining the KEAP1-PGAM5 interaction.
In neonatal mice and a rat cardiomyocyte line exposed to high oxygen (hyperoxia), researchers found that MOTS-c lessened oxidative cardiac injury, and that serum MOTS-c fell with hyperoxia. They attribute the protection to inhibition of oxeiptosis, a reactive-oxygen-driven form of cell death, via preservation of the KEAP1-PGAM5 interaction; forcing KEAP1 expression abolished the benefit, supporting KEAP1 as the target. This is a mechanistic, single-model preclinical study. These are preclinical findings; human data are needed before any clinical conclusions can be drawn, and the term "therapeutic agent" in the abstract reflects the authors' framing, not demonstrated clinical benefit. It is consistent with MOTS-c's recurring antioxidant, mitochondria-protective role in animal tissue-injury models.
Life sciencesn=—AnimalAug 1, 2026 - Study · MOTS-cWeak / none
Mitochondrial-derived peptide MOTS-c targets SLC7A11 to preserve spermatogenesis by suppressing ferroptosis.
A preclinical study on MOTS-c and sperm production. The authors report that serum MOTS-c was lower in men with oligoasthenozoospermia and correlated with semen quality, then used a mouse mechanical-stress (microgravity) model to show spermatogenic impairment. Exogenous MOTS-c was associated with reduced oxidative stress and ferroptosis and better-preserved spermatogenesis, with SLC7A11 identified as a molecular target through loss- and gain-of-function experiments. These are preclinical findings plus a human correlation; human interventional data are needed before clinical conclusions can be drawn. Key caveats: the human component is observational and correlational (low MOTS-c associates with poorer semen quality, which does not establish direction or cause), and the therapeutic effect is demonstrated only in a mouse stress model. For a tracked peptide this is a mechanistically detailed but early signal for MOTS-c in male fertility, hypothesis-generating, not clinical evidence.
Free radical biology & medicinen=—AnimalJul 1, 2026 - Study · MOTS-cWeak / none
LAT1-mediated delivery of engineered R13A-MOTS-c attenuates radiation-induced lung injury via Nrf2 activation and mitochondrial protection.
A preclinical study engineering a modified MOTS-c (R13A-MOTS-c) to improve cell uptake, then testing it against radiation-induced lung injury. In cells and in C57BL/6 mice given thoracic irradiation, daily intraperitoneal R13A-MOTS-c (5 mg/kg for two weeks) was associated with reduced lung inflammation, oxidative stress and mitochondrial dysfunction, with effects tied to activation of the Nrf2 antioxidant pathway and lost when Nrf2 or the LAT1 transporter were blocked. These are preclinical findings; human data are needed before clinical conclusions can be drawn. Two specifics matter for readers: the agent is an engineered analog, not native MOTS-c, so results may not transfer to the unmodified peptide, and the model is acute radiation injury in mice. This is a mechanistically detailed signal for MOTS-c-based approaches, useful as hypothesis-generating context, not evidence of benefit in people.
Redox biologyn=—AnimalJul 1, 2026 - Study · MOTS-cMixed
Mitochondrial-derived peptide MOTS-c activates metabolic signaling but blunts reparative function in human mesenchymal stromal cells.
This is a notable counter-signal study on MOTS-c, the mitochondrial-derived peptide often framed as an exercise-mimetic metabolic regulator. Using adipose-derived mesenchymal stromal cells from people with obesity and lean donors, plus a mouse kidney-stenosis model, researchers reported that exogenous MOTS-c did activate AMPK signaling but paradoxically reduced cell proliferation, increased senescence markers (p16, p21) and TNF-alpha, and, in vivo, failed to improve kidney perfusion, fibrosis or injury, while also blunting the reparative efficacy of lean-donor cells. The message is that metabolic activation did not translate to improved regenerative function and may have worsened senescence and inflammation. It is preclinical (human cells plus mouse model), but a well-constructed cautionary data point against assuming MOTS-c is uniformly beneficial. These are preclinical findings; human data are needed before clinical conclusions can be drawn.
Inflammation and regenerationn=—AnimalJun 22, 2026 - Study · MOTS-cWeak / none
Mitochondrial peptide MOTS-c suppresses systemic and cardiac inflammasome activation in a diabetic rat model.
In a high-fat-diet/streptozotocin rat model of type-2 diabetes, researchers reported that MOTS-c treatment lowered fasting blood glucose and C-reactive protein, modulated inflammatory cytokines (IL-10, IL-1beta), and reduced NLRP3-inflammasome components (NLRP3, ASC, cleaved caspase-1) in heart tissue. They frame this as MOTS-c dampening systemic and cardiac inflammation relevant to diabetic cardiomyopathy. It is a single preclinical rodent study with biochemical and immunohistochemical endpoints, mechanistically consistent with MOTS-c's proposed metabolic and anti-inflammatory roles but far from clinical proof, and it should be read alongside the counter-signal stromal-cell study in this batch showing context-dependent effects. These are preclinical findings; human data are needed before clinical conclusions can be drawn.
Experimental physiologyn=—AnimalJun 19, 2026 - Study · MOTS-cWeak / none
MOTS-c, a mitochondrial-derived peptide, ameliorates lysosomal membrane permeability and improves survival of soft tissue transplantation.
In an animal ischemic-flap model, researchers report that MOTS-c improved blood perfusion and tissue survival, reducing endothelial cell death (pyroptosis), enhancing autophagy, and limiting lysosomal membrane damage. Mechanistically they trace the effect to suppression of PLA2G4A via a MAPK-NF-kB cascade, supported by gene-overexpression experiments. This is a mechanism-heavy, single-model preclinical study; it establishes plausible pathways, not clinical benefit. These are preclinical findings, and human data would be needed before any conclusions about reconstructive surgery could be drawn. It fits the broader MOTS-c pattern of protecting stressed tissue by stabilising mitochondrial and lysosomal function, but the specificity of the proposed PLA2G4A axis rests on this one dataset and warrants independent replication.
Autophagyn=—AnimalJun 2, 2026 - Study · MOTS-cWeak / none
MOTS-c preserves mitochondrial subpopulation bioenergetics and genome integrity to attenuate cardiac ischemia reperfusion injury.
In an isolated (Langendorff-perfused) rat heart model, researchers found that MOTS-c, given before ischaemia or at reperfusion, improved post-ischaemic mechanical recovery and partly preserved mitochondrial function after ischaemia-reperfusion injury. The design is mechanistic and ex vivo: female Wistar rat hearts, six per group, studied outside the body, so systemic and long-term effects are not captured. Effects varied across mitochondrial subpopulations and parameters, and the authors note the signalling mechanism still needs validation. These are preclinical findings; human data are needed before any clinical conclusions can be drawn. The result is consistent with a recurring MOTS-c theme, cardioprotection against ischaemic and oxidative stress in animal hearts, but replication in small isolated-organ models does not substitute for controlled human trials, of which there are none for exogenous MOTS-c.
Molecular biology reportsn=—AnimalJun 2, 2026 - Study · MOTS-cMixed
Reduced Circulating MOTS-c Levels in Hashimoto's Thyroiditis Reflect Integrated Autoimmune and Metabolic Dysregulation: A Cross-Sectional Study.
This cross-sectional human study measured circulating MOTS-c in 90 patients with Hashimoto's thyroiditis versus 90 matched controls, finding significantly lower MOTS-c in patients and inverse correlations with BMI, fasting glucose, HbA1c, HOMA-IR, TSH, CRP and thyroid autoantibodies; regression flagged Hashimoto's and insulin resistance as independent predictors of lower MOTS-c. Importantly, this examines endogenous MOTS-c as a biomarker, not MOTS-c supplementation, so it speaks to associations rather than to peptide administration. A cross-sectional design cannot establish direction or causation (low MOTS-c could be consequence, not cause). It is genuine human data relevant to MOTS-c biology, but should not be read as evidence that taking MOTS-c does anything. Associational human evidence only.
Journal of clinical medicinen=—HumanMay 22, 2026 - Study · MOTS-cMixed
MOTS-c is associated with oxidative stress and arterial stiffness in peritoneal dialysis patients: a pilot study.
This small pilot in 32 peritoneal-dialysis patients measured MOTS-c across serum, urine, and dialysate and correlated it with oxidative stress and arterial stiffness. The findings are mixed and compartment-specific: higher urinary MOTS-c went with lower oxidative stress but greater arterial stiffness, while higher dialysate MOTS-c tracked with a better vascular profile. With 32 participants and no follow-up, this is hypothesis-generating and correlational; it cannot establish whether MOTS-c is protective, compensatory, or simply a marker. The authors themselves frame it as a proposed "mitochondrial-vascular axis." Weight it lightly: a directionally inconsistent pilot in a niche population, useful mainly for flagging that MOTS-c compartmentalisation in uraemia deserves larger study.
International urology and nephrologyn=——May 13, 2026 - Study · MOTS-cWeak / none
Humanin and MOTS-c Attenuate Atrial Fibrillation by Suppressing Fibrosis and Mitochondrial Dysfunction.
This study pairs a small human association analysis with mouse and cell experiments on humanin and MOTS-c in atrial fibrillation (AF). In matched human samples (39 AF patients, 39 controls) plasma MOTS-c was lower in AF and tracked inversely with fibrosis and NT-proBNP. The causal work is preclinical: in an angiotensin-II mouse model and in rat cardiac cells, MOTS-c (and a humanin analogue) reduced AF inducibility and attenuated fibrosis and mitochondrial dysfunction. The human arm is cross-sectional and cannot establish direction; the interventional evidence is animal only. These are largely preclinical findings, and the authors call for larger cohorts and mechanistic follow-up. Read this as an early, internally consistent signal that MOTS-c is reduced in AF and modifies fibrosis pathways in animals, not as evidence for use in patients.
Biomedicinesn=—AnimalMay 5, 2026 - Study · SS-31Weak / none
Safety and Efficacy of Approved and Unapproved Peptide Therapies for Musculoskeletal Injuries and Athletic Performance.
This narrative review in Sports Medicine surveys the pharmacological profiles, regulatory standing, and safety data for eleven peptides marketed to athletes and patients seeking injury recovery — ranging from FDA-approved tesamorelin to unapproved compounds such as BPC-157, TB-500, and MOTS-c. The authors' central finding is that a substantial regulatory gap exists: while some peptides (tesamorelin, sermorelin historically) have cleared rigorous approval processes for specific indications, many others circulate in a gray market supported primarily by animal-model data and amplified by social media. A narrative review design is worth flagging. Unlike a systematic review or meta-analysis, it does not involve exhaustive literature search protocols or pooled effect-size estimates, which means it reflects editorial judgment about which evidence to emphasise. That is appropriate for a broad landscape survey but limits the precision of any efficacy conclusions. The key caveat — which the authors acknowledge directly — is that favorable preclinical signals in rodent tissue-repair and metabolic models do not reliably translate to human outcomes. The review also raises an...
Sports medicine (Auckland, N.Z.)n=——Apr 12, 2026 - Study · MOTS-cContradicted
Are serum MOTS-c levels and MOTS-c m.1382A>C polymorphism related to polycystic ovary syndrome?
This case-control study asked whether serum MOTS-c or the m.1382A>C MOTS-c polymorphism differed in adolescents with polycystic ovary syndrome (PCOS). The answer was largely negative: MOTS-c was slightly higher in PCOS but did not reach significance (p=0.059), showed no associations with metabolic parameters, and every participant carried the wild-type genotype, so the polymorphism could not be assessed. With 121 PCOS and 125 control adolescents this is a reasonably sized, cleanly reported null. The authors conclude MOTS-c likely plays only a minor role in PCOS pathophysiology. Null findings like this are valuable: they counterbalance the more enthusiastic MOTS-c literature and suggest that any MOTS-c/PCOS link, if real, is weak in adolescents. Worth publishing precisely because it tempers overstatement.
Archives of endocrinology and metabolismn=—HumanApr 7, 2026 - Study · GlutathioneWeak / none
Exogenous MOTS-c mitigates myocardial ischemia-reperfusion injury: experimental and in silico evidence from rat heart models.
This proof-of-concept study sought an optimal cardioprotective dose of MOTS-c in isolated rat hearts subjected to ischaemia-reperfusion, supported by molecular docking. Researchers report that 0.5 mg/kg gave maximal protection, a 73% reduction in infarct size versus injury alone, with improved haemodynamics, lower lactate dehydrogenase release, boosted antioxidant defences, and downregulated pro-apoptotic genes. The dose-response framing is genuinely useful for the field. But this is an ex vivo, single-model study; the authors themselves flag the lack of systemic influences and limited dose range, and call for pharmacokinetic and broader dosing work. These are preclinical findings; human data are needed before any clinical conclusions. It strengthens the animal cardioprotection signal while being refreshingly explicit about its own limits.
Naunyn-Schmiedeberg's archives of pharmacologyn=—AnimalApr 1, 2026 - Study · MOTS-cWeak / none
MOTS-c attenuates cardiac dysfunction following high altitude exposure by promoting mitophagy.
This study modelled high-altitude cardiac dysfunction in mice and found it persisted after return to lower altitude, alongside sustained MOTS-c deficiency. Exogenous MOTS-c during de-acclimatisation improved cardiac function by activating the Pink1/Parkin mitophagy pathway; silencing Pink1 abolished the benefit, a solid causal check. The authors also observed lower circulating MOTS-c in patients with high-altitude heart disease and acute coronary syndrome, an association, not proof. This is primarily a single-model preclinical study; these are preclinical findings, and human data are needed before any clinical conclusions. It reinforces MOTS-c's recurring role in maintaining mitochondrial quality through mitophagy in stressed hearts, a coherent mechanism that nonetheless awaits human interventional testing.
Free radical biology & medicinen=—AnimalApr 1, 2026 - Study · MOTS-cWeak / none
Mitochondria-derived peptide MOTS-c alleviates hyperoxia-induced bronchopulmonary dysplasia in neonatal mice by activating Nrf2 pathway.
In a neonatal-mouse model of hyperoxia-induced bronchopulmonary dysplasia and in cultured endothelial cells, researchers found that MOTS-c reduced lung structural damage, inflammation, and oxidative stress, and that the animals' own MOTS-c was depleted by hyperoxia. The benefit was Nrf2-dependent: an Nrf2 inhibitor or Nrf2-deficient mice abolished it, a reasonably rigorous causal check. Still, this is a single-model preclinical study. These are preclinical findings; human data are needed before any clinical conclusions can be drawn, and the abstract's framing of MOTS-c as a "potential therapeutic agent" is a hypothesis, not a demonstrated treatment. It reinforces the consistent theme of MOTS-c acting through Nrf2-linked antioxidant defences in animal injury models.
European journal of pharmacologyn=—AnimalMar 28, 2026 - Study · MOTS-cWeak / none
MOTS-c improves intrinsic muscle mitochondrial bioenergetic health and efficiency in a PGC-1α/AMPK-dependent manner.
Using two transgenic mouse strains, researchers show MOTS-c enhances skeletal-muscle mitochondrial bioenergetics in a way that depends on both PGC-1alpha and AMPK, and lowers mitochondrial reactive-oxygen emission, apparently through intrinsic mitochondrial changes rather than increased mitochondrial content. The genetic dissection is a strength. A human observation is included and notably negative: during one-legged knee-extensor exercise, no arterio-venous MOTS-c difference appeared, suggesting muscle may not be the source of exercise-induced circulating MOTS-c, a useful corrective to a common assumption. Still, the core findings are preclinical; human data are needed before clinical conclusions. It deepens mechanistic understanding of MOTS-c's exercise-mimetic effects while tempering claims about where circulating MOTS-c originates.
Free radical biology & medicinen=—AnimalMar 16, 2026 - Study · MOTS-cWeak / none
A mitochondrial-derived peptide MOTS-c contributes to the protective effect against brain injury associated with LPS-induced sepsis by strengthening the blood-brain barrier's ultrastructure.
In a mouse model of LPS-induced sepsis, researchers report that MOTS-c pretreatment improved survival and sepsis scores, reduced brain-tissue damage and neuroinflammation, and limited blood-brain-barrier permeability, with corresponding changes in barrier-related proteins and neurotrophic factors. This is a single-model preclinical study using pretreatment before sepsis induction, which is mechanistically informative but far from a clinical scenario. These are preclinical findings; human data are needed before any clinical conclusions can be drawn. It extends MOTS-c's anti-inflammatory, tissue-protective profile into sepsis-associated brain injury, consistent with its broader animal literature, but the protective framing rests on this one dataset and a prophylactic dosing design that does not mirror how sepsis presents clinically.
The International journal of neurosciencen=—AnimalMar 1, 2026 - Study · MOTS-cWeak / none
Mitochondrial-derived microproteins in lung disease: insights and implications.
This review, co-authored by figures central to the MDP field, maps what is and isn't known about mitochondrial-derived peptides, MOTS-c and humanin foremost, in lung homeostasis and disease. Its value is honest gap-identification: most MDP work has centred on heart, muscle, brain, and age-related disease, leaving pulmonary roles underexplored. There are no new data; the piece is a research agenda rather than evidence of benefit. For MOTS-c specifically it signals an emerging, still-thin area. Publishable as landscape context that helps readers calibrate how early the MOTS-c-in-lung story is, while making clear no clinical claims follow from it.
American journal of physiology. Lung cellular and molecular physiologyn=——Mar 1, 2026 - Study · MOTS-cWeak / none
Therapeutic Effects of MOTS-c in the Valproic Acid-Induced Autism Model in Rats: Role of Tetrahydrobiopterin and Brain-Derived Neurotrophic Factor.
In a valproic-acid rat model of autism, researchers report that MOTS-c reversed several features, impaired sociability, repetitive behaviour, Purkinje-cell loss, and prefrontal oxidative damage, though not anxiety or neocortical damage. Contrary to their hypothesis, MOTS-c did not raise plasma BH4 or BDNF, so the mechanism appears independent of those messengers. This is a single-model preclinical study with partial, mixed effects and an unconfirmed mechanism. These are preclinical findings; human data are needed before any clinical conclusions can be drawn. MOTS-c is generally reported not to cross the blood-brain barrier, which the authors note, making the central effects intriguing but requiring explanation. Weight this as an early, incomplete animal signal, not evidence relevant to people.
Molecular neurobiologyn=—AnimalFeb 18, 2026 - Study · MOTS-cMixed
Reduced serum and skeletal muscle MOTS c levels in women with polycystic ovary syndrome are associated with mitochondrial dysfunction.
This case-control study found that women with PCOS had lower circulating MOTS-c (220 vs 498 pg/mL) and lower skeletal-muscle MOTS-c than matched controls, with serum levels inversely associated with testosterone and cholesterol. The muscle-biopsy confirmation adds a compartment-level dimension beyond blood. Still, this is observational: 40 versus 40 participants, cross-sectional, so direction and causation are unresolved. Notably it points the opposite way to an adolescent PCOS study reporting no significant MOTS-c difference, underscoring genuine mixed signals in the MOTS-c/PCOS literature. Weight it as a plausible association, MOTS-c is reduced in this adult PCOS sample, that needs larger, prospective confirmation before any interpretive weight is placed on it.
Scientific reportsn=—HumanFeb 12, 2026 - Study · MOTS-cWeak / none
Mitochondrial-derived microproteins in cancer and neurodegeneration: A new era of cross-disease mechanistic insights.
This review examines how mitochondrial-derived microproteins, humanin, MOTS-c, SHLPs, and the newer SHMOOSE, translate mitochondrial stress into cell-fate decisions across ageing, cancer, and neurodegeneration. MOTS-c is covered at the pathway level (AMPK/NRF2-LARS1/mTORC1), and the piece usefully frames context-dependence: the same peptides can be protective in neurons yet co-opted by tumours. As a synthesis it aggregates mechanism rather than testing outcomes, and it makes no clinical efficacy claims. For MOTS-c readers it offers a coherent map of signalling architecture and the intriguing cancer-versus-Alzheimer's inverse-comorbidity angle. Publishable as advanced landscape context, with the standing caveat that these are mechanistic and preclinical insights, not evidence of therapeutic benefit.
Pathology, research and practicen=——Feb 1, 2026 - Study · MOTS-cWeak / none
Mitochondria-derived peptides in liver disease: Emerging regulators of hepatic metabolism and therapeutic targets.
This review synthesises the role of mitochondrial-derived peptides, humanin, MOTS-c, and SHLPs, in liver homeostasis and disease. MOTS-c features substantially: the authors describe it activating AMPK, regulating nuclear gene expression, and suppressing fibrotic and inflammatory signalling in models of metabolic dysfunction-associated steatotic liver disease (MASLD) and fibrosis. As a review it aggregates preclinical mechanism rather than testing outcomes, and the human evidence base for MOTS-c in liver disease remains thin. There are no clinical efficacy data here. Publishable as orientation for readers tracking MOTS-c's hepatic biology, with the clear caveat that it summarises emerging preclinical signals, not established therapy.
Hepatology communicationsn=——Feb 1, 2026 - Study · MOTS-cMixed
Systemic MOTS-c levels are increased in adults with obesity in association with metabolic dysregulation and remain unchanged after weight loss.
This exploratory human study reports that circulating MOTS-c was higher in adults with obesity than lean controls (273 vs 223 pg/mL), with BMI and insulin resistance independently predicting elevated levels and a nonlinear, biphasic relationship with HOMA-IR. In 10 patients followed after bariatric surgery, MOTS-c did not change despite major weight loss, and adipose-tissue MOTS-c neither differed by group nor tracked with blood levels. The authors frame elevated MOTS-c as a possible compensatory response. This is a small, cross-sectional-plus-brief-longitudinal observational study; associations cannot establish causation. It usefully complicates the MOTS-c picture: contrast with reports of reduced MOTS-c in PCOS and other states shows the direction is context-dependent. Weight it as hypothesis-generating and explicitly awaiting larger validation.
Journal of clinical & translational endocrinologyn=——Feb 1, 2026 - Study · MOTS-cWeak / none
Mitochondrial-derived peptides MOTS-c and humanin attenuate dexamethasone-induced atrophy in human skeletal muscle cells.
Using human skeletal-muscle cells (myotubes), researchers tested whether MOTS-c and a humanin analogue (HNG) counter dexamethasone-induced muscle wasting. MOTS-c co-treatment fully preserved myotube size and the fusion index, increased Akt signalling, and blunted the atrophy driver MURF1 and STAT3 activation; HNG preserved size but had narrower effects. Notably these are human-derived cells, which strengthens translational relevance over rodent work, but it remains in vitro: no living organism, no dosing, no systemic context. These are preclinical findings; human clinical data are needed before conclusions can be drawn. The signal, MOTS-c limiting glucocorticoid-driven atrophy pathways, is mechanistically coherent and consistent with MOTS-c's exercise-mimetic reputation, but stands on a single cell-culture experiment.
Physiological reportsn=—In vitroFeb 1, 2026 - Study · MOTS-cWeak / none
Muscle-Targeted Nanocomposite Therapy Alleviates Age-Related Sarcopenia via Antioxidant and Metabolic Reprogramming.
This study engineers a muscle-targeted nanocomposite pairing MOTS-c with antioxidant black phosphorus nanosheets and tests it in cell and mouse models of age-related sarcopenia. Researchers report that the combination reduced muscle dysfunction and loss, restored mitochondrial function, and lowered lipid peroxidation, acting through PI3K/AKT/Nrf2 activation and suppression of ROS/p38 MAPK signalling. The novelty is delivery: MOTS-c bundled into a targeted, ROS-scavenging carrier. It remains a single-model preclinical study, and the nanocomposite's effects cannot be neatly separated from MOTS-c alone. These are preclinical findings; human data are needed before any clinical conclusions. It advances the MOTS-c-for-muscle theme into materials science, an interesting direction that is still far from patients.
ACS nanon=—AnimalJan 13, 2026 - Study · MOTS-cWeak / none
MOTS‑c protects against placental injury via Nrf2 activation in hypoxia‑induced intrauterine growth restriction mice.
In a mouse model of hypoxia-induced intrauterine growth restriction, researchers found placental MOTS-c was reduced and correlated with lower fetal weight, and that giving MOTS-c attenuated growth restriction by promoting placental angiogenesis and reducing oxidative-stress-driven placental dysfunction. The mechanism was Nrf2-dependent: MOTS-c lost its effect in Nrf2-knockout mice and in cells treated with an Nrf2 inhibitor, a strong causal check. This remains a single-model preclinical study; these are preclinical findings, and human data are needed before any clinical conclusions can be drawn. It is consistent with the recurring MOTS-c theme of Nrf2-linked antioxidant protection in tissue under oxidative stress, here extended to placental biology, but it carries no implications for human pregnancy at this stage.
International journal of molecular medicinen=—AnimalJan 1, 2026 - Study · MOTS-cWeak / none
Aerobic exercise and MOTS-c attenuate diabetic myocardial fibrosis via inhibition of the THBS1/TGF-β signaling pathway.
This preclinical study compared aerobic exercise and MOTS-c on diabetic myocardial fibrosis. Researchers report both reduced collagen buildup, improved glucose and lipid handling, and enhanced systolic and diastolic heart function, apparently by suppressing the THBS1/TGF-beta signalling pathway identified via transcriptomics. The framing, MOTS-c as a stand-in for exercise, is an appealing but still preclinical hypothesis. The abstract omits species and sample details, and the work rests on a single experimental model with mechanistic (mRNA/protein) confirmation. These are preclinical findings; human data are needed before any clinical conclusions. It sits within the recurring MOTS-c narrative as an exercise-mimetic with cardiometabolic effects in animals, promising as a research direction, not a therapy.
Frontiers in endocrinologyn=—AnimalJan 1, 2026 - Study · MOTS-cWeak / none
MOTS-c Protects Against Acetaminophen-induced Liver Injury through the MAPK Signaling Pathway.
In a mouse model of acetaminophen-induced liver injury, researchers found that MOTS-c lowered markers of liver damage (AST, ALT), suppressed inflammatory signalling, restored glutathione, and reduced oxidative stress and hepatocyte death. Both plasma and liver MOTS-c were depleted by acetaminophen. Mechanistically the effect ran through inhibition of MAPK components (ERK, JNK, p38), and co-treatment with MAPK inhibitors abolished the protection, a useful causal check. This remains a single-model preclinical study. These are preclinical findings; human data are needed before any clinical conclusions, and "promising therapeutic candidate" is the authors' framing, not evidence of benefit in people. It fits the broader MOTS-c pattern of easing oxidative and inflammatory tissue injury in rodents.
Protein and peptide lettersn=—AnimalJan 1, 2026 - Study · MOTS-cWeak / none
MOTS-c primes adrenal cortex metabolism without directly driving steroidogenesis.
In adult male Wistar rats (n=16) given continuous MOTS-c for 24 hours, researchers found that MOTS-c did not change steroidogenic genes or circulating corticosterone and aldosterone, but instead shifted metabolic gene expression, upregulating a purinergic receptor and calcium signalling while dampening stress markers and mitophagy. Their interpretation is that MOTS-c "primes" adrenal cells for later stimulation rather than driving hormone output. This is a small, short-duration, single-model preclinical study; it opens a novel line of adrenal biology but is far from clinical relevance. These are preclinical findings; human data would be needed before any conclusions. Notably, the study is careful and partly null, an antidote to overreach about MOTS-c as a hormonal driver.
Folia histochemica et cytobiologican=—AnimalJan 1, 2026 - Study · MOTS-cWeak / none
MOTS-c attenuates mitochondrial dysfunction induces pyroptosis and cartilage degradation in osteoarthritis via an Nrf2-Dependent Mechanism.
In cell experiments and a mouse osteoarthritis model, researchers report that MOTS-c improved mitochondrial dysfunction, inhibited inflammasome activation, and reduced chondrocyte pyroptosis, helping preserve cartilage extracellular matrix and limit matrix-degrading enzymes. They attribute this to the Nrf2/TXNIP/NLRP3 axis, and report that MOTS-c slowed cartilage degeneration on imaging and histology. This is a single-model preclinical study combining in-vitro and in-vivo work; it establishes plausible mechanism, not clinical benefit. These are preclinical findings; human data are needed before any conclusions about osteoarthritis in people. It extends MOTS-c's Nrf2-linked, anti-inflammatory, mitochondria-protective profile into joint tissue, consistent with the peptide's broader animal literature but not yet translatable.
Free radical biology & medicinen=—AnimalDec 16, 2025 - Study · MOTS-cMixed
Circulating Mitochondrial Open Reading Frame of the 12S Ribosomal RNA Type-c Is Higher in Acute Coronary Syndrome and Is a Prognostic Biomarker for Major Cardiac Events in Patients With Acute Myocardial Infarction: A Case-Control Study.
In a 400-subject case-control study, researchers found circulating MOTS-c was higher in acute coronary syndrome and, combined with an oxidative-stress marker, predicted major adverse cardiac events over 18 months. In-vitro work suggested oxidative stress induces MOTS-c while MOTS-c in turn reduces hypoxia-induced oxidative stress. The larger sample and prospective outcome tracking are strengths. But direction is complicated: here MOTS-c is elevated in disease, whereas other cardiac studies report it reduced, reinforcing that MOTS-c's biomarker behaviour is context-dependent and possibly compensatory. Associations cannot establish causation. Weight it as one of the sturdier human MOTS-c biomarker datasets while recognising it deepens, rather than resolves, the mixed cardiac picture.
Journal of the American Heart Associationn=—HumanDec 16, 2025 - Study · MOTS-cWeak / none
Repeated Heat Stress Modulates the Levels of the Mitokines MOTS-C and FGF21 in Active Men during Calf Muscle Immobilization.
This is a small randomized human trial (19 active men) testing whether repeated heat exposure alters mitokine responses during two weeks of calf immobilization. MOTS-c features as an outcome, not an intervention: heat treatment raised circulating MOTS-c and lowered skeletal-muscle FGF21, while immobilization itself did not change mitokine levels. The randomized design and human setting are strengths, but the sample is small and the endpoint is a biomarker, not a clinical outcome. No MOTS-c was administered, so this speaks to how MOTS-c behaves as a stress-responsive signal, not to MOTS-c as a therapy. Publishable as a directly relevant human observation, weighted modestly: it shows heat can modulate MOTS-c much as exercise reportedly does, reinforcing its exercise-mimetic biology.
Medicine and science in sports and exercisen=—HumanDec 1, 2025 - Study · MOTS-cWeak / none
Mitochondrial-Derived Peptides: Implication in the Therapy of Neurodegenerative Diseases.
This systematic-style review evaluates mitochondrial-derived peptides, humanin, MOTS-c, and SHLPs, as candidates in Alzheimer's, Parkinson's, and Huntington's disease. MOTS-c features among the peptides discussed for antioxidant, neuroprotective, and anti-inflammatory mechanisms across disease models. The authors are candid that the field is limited by unclear molecular pathways, delivery challenges, and a lack of clinical translation, and much MOTS-c neuro work must contend with its reported poor blood-brain-barrier penetration. As a review it aggregates preclinical signals rather than testing outcomes, and makes no clinical claims. Publishable as orientation for readers tracking MOTS-c in neurodegeneration, with clear framing that this is an early, mechanism-level research area.
Molecular neurobiologyn=——Dec 1, 2025 - Study · MOTS-cWeak / none
MOTS-c in type 2 diabetes mellitus: From risk factors to cardiac complications and potential treatment.
This review centres squarely on MOTS-c in type 2 diabetes, from risk factors through cardiac complications, and usefully compiles the exogenous MOTS-c dosing approaches used across preclinical metabolic studies, a practical reference for the field. Its thesis is that insufficient MOTS-c from dysfunctional mitochondria contributes to diabetes and its complications via retrograde signalling. As a review it synthesises mechanism and association rather than demonstrating outcomes, and the therapeutic evidence it draws on is preclinical. No human efficacy data are presented, and the dosing summaries describe animal protocols, not clinical guidance. Publishable as directly relevant landscape context with clear framing that MOTS-c in diabetes remains a preclinical, mechanism-and-biomarker story awaiting human trials.
Life sciencesn=——Dec 1, 2025 - Study · MOTS-cMixed
Insights into the Biomarker Potential of Humanin and Mots-c Expression and Telomere Length in Alzheimer's Disease.
This case-control study evaluated humanin and MOTS-c as potential Alzheimer's biomarkers, comparing patients with Alzheimer's, mild cognitive impairment, and subjective cognitive decline controls. Researchers found that blood/plasma transcript (gene-expression) levels of both peptides were reduced in Alzheimer's, while plasma protein concentrations did not discriminate Alzheimer's from mild cognitive impairment, an important discordance between mRNA and protein. This is observational and cross-sectional; it identifies associations, not causes, and the protein-level null tempers enthusiasm. It fits the broader pattern that MOTS-c tends to decline with age and neurodegeneration, but the mixed transcript-versus-protein signal means any biomarker role is preliminary. Publishable as a directly relevant human dataset, weighted as early and internally mixed.
International journal of molecular sciencesn=—HumanNov 9, 2025 - Study · MOTS-cWeak / none
Serum Mitochondrial Open Reading Frame of the 12S rRNA-c (MOTS-c) Dynamics as a Complementary Marker of Treatment Response in Newly Diagnosed Multiple Myeloma: A Prospective Analysis.
This small prospective cohort measured serum MOTS-c before and after frontline treatment in 29 newly diagnosed multiple myeloma patients. Researchers report that treatment responders showed a substantial post-therapy rise in MOTS-c while refractory cases changed little, and post-treatment levels correlated inversely with calcium and neutrophil changes. The authors are appropriately modest: MOTS-c had limited standalone predictive value and they position it only as a possible complementary marker of response. With 29 patients this is exploratory; associations cannot establish causation and require validation in larger cohorts. It extends MOTS-c's biomarker story into oncology, where the peptide has a dual and context-dependent literature, but the signal here is preliminary and should be weighted accordingly.
Cureusn=—HumanNov 1, 2025 - Study · MOTS-cMixed
MOTS-C levels ın ındividuals with and without obesity and ıts association with ınflammation, insulin resistance and endothelial dysfunction.
This cross-sectional study measured serum MOTS-c in 48 adults with obesity and 37 with normal BMI, alongside markers of insulin resistance, inflammation, and endothelial function. It found no significant difference in MOTS-c between groups, but a positive correlation with insulin resistance (HOMA-IR); regression flagged age (inverse) and HOMA-IR (positive) as determinants. This is observational and cannot establish causation. It directly contradicts reports of clearly elevated (or reduced) MOTS-c in obesity, underscoring how inconsistent the human MOTS-c-obesity literature is. Publishable precisely because a well-reported null adds needed balance: MOTS-c may track insulin resistance more than adiposity itself, and no strong obesity signal emerged here. Weight it as one data point in a genuinely mixed evidence base.
Archives of endocrinology and metabolismn=——Sep 26, 2025 - Study · MOTS-cWeak / none
The unexplored Nexus: Mitochondria derived microproteins and Parkinson's disease.
This review argues that mitochondria-derived microproteins, humanin, SHLPs, and MOTS-c, warrant exploration as disease-modifying targets in Parkinson's disease, given the central role of mitochondrial dysfunction, oxidative stress, and neuroinflammation in its pathology. MOTS-c is presented as one of the candidate peptides that could modulate these processes. The piece is explicitly forward-looking and gap-identifying: it notes the area is largely unexplored and offers no primary data. For MOTS-c readers it is on-topic but general, sketching a rationale rather than evidence. Publishable as landscape context, with the caveat that it makes a case for future research rather than demonstrating any MOTS-c effect in Parkinson's, where clinical evidence does not yet exist.
Pathology, research and practicen=——Sep 1, 2025 - Study · MOTS-cWeak / none
Mitochondrial-encoded peptide MOTS-c prevents pancreatic islet cell senescence to delay diabetes.
This study reports that MOTS-c declines with age and senescence in pancreatic islet cells, and that treating aged mouse islets with MOTS-c reduced markers of islet senescence by modulating nuclear gene expression and metabolites. In diabetic mouse models MOTS-c improved islet senescence and glucose intolerance, and in humans circulating MOTS-c was lower in type 2 diabetes than controls, an association. The authors frame MOTS-c as a possible "senotherapeutic." The interventional evidence is preclinical; the human arm is observational. These are preclinical findings; human data are needed before any clinical conclusions, and the abstract's talk of "delaying diabetes" reflects a mouse-model outcome, not demonstrated human benefit. It adds a coherent ageing/senescence angle to the MOTS-c metabolic literature.
Experimental & molecular medicinen=—AnimalAug 1, 2025