Mitochondrial-targeted SS-31 peptide attenuates radiation-induced cardiomyocyte senescence.

Xie L, Wu J, Fan J, Krager KJ, Aykin-Burns N, Li S, Børsheim E, Qi X, Boerma M, Zhang H

Journal of radiation research1 Jul 2026

PMID42456009PMCIDPMC13400571DOI10.1093/jrr/rrag048PepBankPUB-42456009

Summary

Exposure to ionizing radiation, such as from radiation therapy or accidental radiation exposure can have adverse effects on the heart. While radiation injury in the heart may include cardiomyocyte senescence, there are no available strategies to prevent this phenomenon. This study evaluated the effects of the mitochondrial-targeted peptide SS-31 (elamipretide) on radiation-induced cell senescence in cardiomyoblast H9C2 cells and human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs). Exposure to γ-radiation at doses of 2, 5, and 10 Gy inhibited H9C2 cell proliferation in a dose-dependent manner, and induced senescence-associated beta-galactosidase (SA-β-gal) staining, a gold standard of cell senescence. Treatment with SS-31 (1 μM) for 7 days reduced SA-β-gal positive staining from 67% to 38% in H9C2 cells under 10 Gy radiation. SS-31 also prevented increases in the expression of p16 and p21, two well-accepted senescence markers, in irradiated H9C2 cells and hiPSC-CMs. SS-31 decreased the canonical senescence-associated secretory phenotype markers TNF-α, IL-6, and IL-1β. SS-31 also reversed the BAX/bcl-2 ratio, a marker of mitochondrial-related apoptosis. Moreover, SS-31 mitigated mitochondrial production of reactive oxygen species. Interestingly, we found that a dose of 10 Gy increased mitochondrial respiration, and SS-31 reversed this elevation. This study suggests that SS-31 is a promising compound that may prevent radiation-induced cardiomyocyte senescence.

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

Results from this study9

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

01LabIn vitro (cells)Mechanism
In H9C2 cardiomyoblasts exposed to 10 Gy radiation, SS‑31 at 1 µM for 7 days reduced SA-β-gal positive staining from 67% to 38%.
In plain wordsIn heart cells exposed to radiation, SS‑31 lowered a common sign of cell ageing compared with untreated irradiated cells.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseSA-beta-gal positive staining
Study
ratn: not reported in source
H9C2 cells, 10 Gy
Comparator
Irradiated cells without SS-31
Outcome group
Aging markers · Cardiovascular
Studied dose
1 µM · 7 daysAs given in this study (rat).
Measurements
SA-β-gal positive staining
38%
SS-31 1 µM, H9C2, 10 Gy
SA-β-gal positive staining
67%
10 Gy without SS-31
Source sentences
Summary
Treatment with SS-31 (1 μM) for 7 days reduced SA-β-gal positive staining from 67% to 38% in H9C2 cells under 10 Gy radiation.
1 context sentence(design, population, supporting numbers)
Summary · context
This study evaluated the effects of the mitochondrial-targeted peptide SS-31 (elamipretide) on radiation-induced cell senescence in cardiomyoblast H9C2 cells and human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs).
Show in the study text Report a problemFND-4245600901
02LabIn vitro (cells)Mechanism
In irradiated H9C2 cells and hiPSC-CMs, SS‑31 prevented the increase in p16 expression.
In plain wordsIn irradiated heart cells, SS‑31 stopped a rise in p16, a marker of cell ageing.
Peptide
Elamipretide (SS-31)
Outcome
Decreasep16 expression
Study
rat and humann: not reported in source
Irradiated H9C2 cardiomyoblasts and hiPSC-derived cardiomyocytes
Comparator
Irradiated cells without SS-31
Outcome group
Aging markers · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
SS-31 also prevented increases in the expression of p16 and p21, two well-accepted senescence markers, in irradiated H9C2 cells and hiPSC-CMs.
1 context sentence(design, population, supporting numbers)
Summary · context
This study evaluated the effects of the mitochondrial-targeted peptide SS-31 (elamipretide) on radiation-induced cell senescence in cardiomyoblast H9C2 cells and human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs).
Show in the study text Report a problemFND-4245600902
03LabIn vitro (cells)Mechanism
In irradiated H9C2 cells and hiPSC-CMs, SS‑31 prevented the increase in p21 expression.
In plain wordsIn irradiated heart cells, SS‑31 stopped a rise in p21, a marker of cell ageing.
Peptide
Elamipretide (SS-31)
Outcome
Decreasep21 expression
Study
rat and humann: not reported in source
Irradiated H9C2 cardiomyoblasts and hiPSC-derived cardiomyocytes
Comparator
Irradiated cells without SS-31
Outcome group
Aging markers · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
SS-31 also prevented increases in the expression of p16 and p21, two well-accepted senescence markers, in irradiated H9C2 cells and hiPSC-CMs.
1 context sentence(design, population, supporting numbers)
Summary · context
This study evaluated the effects of the mitochondrial-targeted peptide SS-31 (elamipretide) on radiation-induced cell senescence in cardiomyoblast H9C2 cells and human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs).
Show in the study text Report a problemFND-4245600903
04LabIn vitro (cells)Mechanism
SS‑31 decreased the senescence-associated secretory phenotype marker TNF-α in irradiated cardiomyocyte models.
In plain wordsIn irradiated heart cells, SS‑31 lowered TNF-α, an inflammation signal released by ageing cells.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseTNF-alpha (SASP marker)
Study
rat and humann: not reported in source
Irradiated H9C2 cardiomyoblasts and hiPSC-derived cardiomyocytes
Comparator
Irradiated cells without SS-31
Outcome group
Inflammation markers · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
SS-31 decreased the canonical senescence-associated secretory phenotype markers TNF-α, IL-6, and IL-1β.
1 context sentence(design, population, supporting numbers)
Summary · context
This study evaluated the effects of the mitochondrial-targeted peptide SS-31 (elamipretide) on radiation-induced cell senescence in cardiomyoblast H9C2 cells and human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs).
Show in the study text Report a problemFND-4245600904
05LabIn vitro (cells)Mechanism
SS‑31 decreased the senescence-associated secretory phenotype marker IL-6 in irradiated cardiomyocyte models.
In plain wordsIn irradiated heart cells, SS‑31 lowered IL-6, an inflammation signal released by ageing cells.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseIL-6 (SASP marker)
Study
rat and humann: not reported in source
Irradiated H9C2 cardiomyoblasts and hiPSC-derived cardiomyocytes
Comparator
Irradiated cells without SS-31
Outcome group
Inflammation markers · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
SS-31 decreased the canonical senescence-associated secretory phenotype markers TNF-α, IL-6, and IL-1β.
1 context sentence(design, population, supporting numbers)
Summary · context
This study evaluated the effects of the mitochondrial-targeted peptide SS-31 (elamipretide) on radiation-induced cell senescence in cardiomyoblast H9C2 cells and human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs).
Show in the study text Report a problemFND-4245600905
06LabIn vitro (cells)Mechanism
SS‑31 decreased the senescence-associated secretory phenotype marker IL-1β in irradiated cardiomyocyte models.
In plain wordsIn irradiated heart cells, SS‑31 lowered IL-1β, an inflammation signal released by ageing cells.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseIL-1beta (SASP marker)
Study
rat and humann: not reported in source
Irradiated H9C2 cardiomyoblasts and hiPSC-derived cardiomyocytes
Comparator
Irradiated cells without SS-31
Outcome group
Inflammation markers · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
SS-31 decreased the canonical senescence-associated secretory phenotype markers TNF-α, IL-6, and IL-1β.
1 context sentence(design, population, supporting numbers)
Summary · context
This study evaluated the effects of the mitochondrial-targeted peptide SS-31 (elamipretide) on radiation-induced cell senescence in cardiomyoblast H9C2 cells and human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs).
Show in the study text Report a problemFND-4245600906
07LabIn vitro (cells)Mechanism
SS‑31 reversed the BAX/bcl-2 ratio, a marker of mitochondrial-related apoptosis, in irradiated cardiomyocyte models.
In plain wordsIn irradiated heart cells, SS‑31 reversed a marker of mitochondria-related cell death.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseBAX/bcl-2 ratio
Study
rat and humann: not reported in source
Irradiated H9C2 cardiomyoblasts and hiPSC-derived cardiomyocytes
Comparator
Irradiated cells without SS-31
Outcome group
Mitochondrial function · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
SS-31 also reversed the BAX/bcl-2 ratio, a marker of mitochondrial-related apoptosis.
1 context sentence(design, population, supporting numbers)
Summary · context
This study evaluated the effects of the mitochondrial-targeted peptide SS-31 (elamipretide) on radiation-induced cell senescence in cardiomyoblast H9C2 cells and human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs).
Show in the study text Report a problemFND-4245600907
08LabIn vitro (cells)Mechanism
SS‑31 mitigated mitochondrial production of reactive oxygen species in irradiated cardiomyocyte models.
In plain wordsIn irradiated heart cells, SS‑31 reduced harmful reactive oxygen molecules made by mitochondria.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseMitochondrial ROS production
Study
rat and humann: not reported in source
Irradiated H9C2 cardiomyoblasts and hiPSC-derived cardiomyocytes
Comparator
Irradiated cells without SS-31
Outcome group
Mitochondrial function · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
Moreover, SS-31 mitigated mitochondrial production of reactive oxygen species.
1 context sentence(design, population, supporting numbers)
Summary · context
This study evaluated the effects of the mitochondrial-targeted peptide SS-31 (elamipretide) on radiation-induced cell senescence in cardiomyoblast H9C2 cells and human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs).
Show in the study text Report a problemFND-4245600908
09LabIn vitro (cells)Mechanism
SS‑31 reversed the increase in mitochondrial respiration caused by 10 Gy radiation.
In plain wordsIn irradiated heart cells, SS‑31 reversed the rise in mitochondrial oxygen use caused by radiation.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseMitochondrial respiration after 10 Gy
Study
rat and humann: not reported in source
Irradiated H9C2 cardiomyoblasts and hiPSC-derived cardiomyocytes
Comparator
Irradiated cells without SS-31
Outcome group
Mitochondrial function · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
Interestingly, we found that a dose of 10 Gy increased mitochondrial respiration, and SS-31 reversed this elevation.
1 context sentence(design, population, supporting numbers)
Summary · context
This study evaluated the effects of the mitochondrial-targeted peptide SS-31 (elamipretide) on radiation-induced cell senescence in cardiomyoblast H9C2 cells and human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs).
Show in the study text Report a problemFND-4245600909

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

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