Mitochondrial-encoded peptide MOTS-c prevents pancreatic islet cell senescence to delay diabetes.

Kong BS, Lee H, L'Yi S, Hong S, Cho YM

Experimental & molecular medicine25 Aug 2025Cited by 8 (Europe PMC)

PMID40855115PMCIDPMC12411631DOI10.1038/s12276-025-01521-1PepBankPUB-40855115

Summary

Mitochondria are crucial for cell survival and function, partly through peptides encoded by the mitochondrial genome. Although mitochondrial dysfunction is a hallmark of age-related diseases and senescence, the role of mitochondrial-genome-encoded peptides in pancreatic β-cell senescence during type 1 and type 2 diabetes pathogenesis is largely unexplored. Here we show that MOTS-c levels decrease with aging and senescence in pancreatic islet cells. Treating aged C57BL/6 mouse pancreatic islets with MOTS-c reduced pancreatic islet senescence by modulating nuclear gene expression and metabolites involved in β-cell senescence. MOTS-c treatment improved pancreatic islet senescence and glucose intolerance in S961-treated C57BL/6 and in nonobese diabetic mice. In humans, circulating MOTS-c levels are lower in type 2 diabetes patients compared with healthy controls. Our findings suggest that mitochondrial-encoded MOTS-c regulate pancreatic islet cell senescence and that MOTS-c could act as a senotherapeutic agent to prevent pancreatic islet cell senescence and diabetes progression.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study5

3 results from studies that gave the peptide. No result from this study comes from people.

01AnimalAnimal study (in vivo)Efficacy outcome
MOTS‑c treatment improved pancreatic islet senescence in S961-treated C57BL/6 and nonobese diabetic mice.
In plain wordsIn mice, MOTS‑c reduced aging of pancreatic islet cells.
Peptide
MOTS-c
Outcome
DecreasePancreatic islet senescence in S961-treated and NOD mice
Study
mousen: not reported in source
S961-treated C57BL/6 and nonobese diabetic mice
Outcome group
Aging markers · Endocrine and hormones
Studied dose
Dose not stated
Source sentences
Summary
MOTS-c treatment improved pancreatic islet senescence and glucose intolerance in S961-treated C57BL/6 and in nonobese diabetic mice.
Show in the study text Report a problemFND-4085511503
02AnimalAnimal study (in vivo)Efficacy outcome
MOTS‑c treatment improved glucose intolerance in S961-treated C57BL/6 and nonobese diabetic mice.
In plain wordsIn mice, MOTS‑c improved how well the body handled sugar.
Peptide
MOTS-c
Outcome
DecreaseGlucose intolerance in S961-treated and NOD mice
Study
mousen: not reported in source
S961-treated C57BL/6 and nonobese diabetic mice
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated
Source sentences
Summary
MOTS-c treatment improved pancreatic islet senescence and glucose intolerance in S961-treated C57BL/6 and in nonobese diabetic mice.
Show in the study text Report a problemFND-4085511504
03LabEx vivo tissueEfficacy outcome
Treating aged C57BL/6 mouse pancreatic islets with MOTS‑c reduced islet senescence.
In plain wordsIn lab tests on aged mouse pancreatic islets, MOTS‑c reduced cell aging.
Peptide
MOTS-c
Outcome
DecreaseIslet senescence in aged mouse islets
Study
mousen: not reported in source
aged C57BL/6 pancreatic islets
Outcome group
Aging markers · Endocrine and hormones
Studied dose
Dose not stated
Source sentences
Summary
Treating aged C57BL/6 mouse pancreatic islets with MOTS-c reduced pancreatic islet senescence by modulating nuclear gene expression and metabolites involved in β-cell senescence.
Show in the study text Report a problemFND-4085511502

Natural levels measured2

These results measure the body's own peptide. Nobody was given the peptide. They are not evidence about taking it. They are left out of key results, evidence counts and charts.

04HumanEndogenous levelObservational studyOther
In humans, circulating MOTS‑c levels were lower in patients with type 2 diabetes than in healthy controls.
In plain wordsIn people with type 2 diabetes, the body's own MOTS‑c levels were lower than in healthy people.
Peptide
MOTS-c
Outcome
DecreaseCirculating MOTS-c in type 2 diabetes
Study
n: not reported in source
Comparator
Healthy controls
Outcome group
Glycemic control · Metabolic and weight
Source sentences
Summary
In humans, circulating MOTS-c levels are lower in type 2 diabetes patients compared with healthy controls.
This result measures the body's own MOTS-c. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-4085511505
05LabEndogenous levelEx vivo tissueOther
MOTS‑c levels decreased with aging and senescence in pancreatic islet cells.
In plain wordsIn islet cells, the body's own MOTS‑c fell with aging and cell senescence.
Peptide
MOTS-c
Outcome
DecreaseMOTS-c levels in pancreatic islet cells with aging and senescence
Study
n: not reported in source
pancreatic islet cells
Outcome group
Aging markers · Endocrine and hormones
Source sentences
Summary
Here we show that MOTS-c levels decrease with aging and senescence in pancreatic islet cells.
This result measures the body's own MOTS-c. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-4085511501

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
10 Oct 2026, 08:19 UTC
Study results updated
Version 1
9 Oct 2026, 02:47 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

Publication types

MeSH terms

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