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Study · Animal study (in vivo) · mouse and rat · 2020

5 results

Reduction of elevated proton leak rejuvenates mitochondria in the aged cardiomyocyte.

Zhang H, Alder NN, Wang W, Szeto H, Marcinek DJ, Rabinovitch PS

eLife15 Dec 2020Cited by 96 (Europe PMC)

PMID33319746 (opens in a new tab)PMCIDPMC7738186 (opens in a new tab)DOI10.7554/elife.60827 (opens in a new tab)PepBankPUB-33319746
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Summary

Aging-associated diseases, including cardiac dysfunction, are increasingly common in the population. However, the mechanisms of physiologic aging in general, and cardiac aging in particular, remain poorly understood. Age-related heart impairment is lacking a clinically effective treatment. Using the model of naturally aging mice and rats, we show direct evidence of increased proton leak in the aged heart mitochondria. Moreover, our data suggested ANT1 as the most likely site of mediating increased mitochondrial proton permeability in old cardiomyocytes. Most importantly, the tetra-peptide SS-31 prevents age-related excess proton entry, decreases the mitochondrial flash activity and mitochondrial permeability transition pore opening, rejuvenates mitochondrial function by direct association with ANT1 and the mitochondrial ATP synthasome, and leads to substantial reversal of diastolic dysfunction. Our results uncover the excessive proton leak as a novel mechanism of age-related cardiac dysfunction and elucidate how SS-31 can reverse this clinically important complication of cardiac aging.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study5

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

  1. 01AnimalAnimal study (in vivo)Mechanism

    In aged mice and rats, SS‑31 prevented the age-related excess proton entry into heart mitochondria.

    In plain wordsIn aged mice and rats, SS‑31 prevented the extra proton leak seen in old heart mitochondria.

    Peptide
    Elamipretide (SS-31)
    Outcome
    DecreaseAge-related excess proton leak
    Study

    mice and ratsn: not reported in source

    naturally aging heart
    Outcome group
    Mitochondrial function · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    the tetra-peptide SS-31 prevents age-related excess proton entry
    1 context sentence
    Summary · context
    Using the model of naturally aging mice and rats, we show direct evidence of increased proton leak in the aged heart mitochondria.
  2. 02AnimalAnimal study (in vivo)Mechanism

    In aged mice and rats, SS‑31 decreased mitochondrial flash activity.

    In plain wordsIn aged mice and rats, SS‑31 lowered mitochondrial flash activity in the heart.

    Peptide
    Elamipretide (SS-31)
    Outcome
    DecreaseMitochondrial flash activity
    Study

    mice and ratsn: not reported in source

    naturally aging heart
    Outcome group
    Mitochondrial function · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    decreases the mitochondrial flash activity and mitochondrial permeability transition pore opening
    1 context sentence
    Summary · context
    Using the model of naturally aging mice and rats, we show direct evidence of increased proton leak in the aged heart mitochondria.
  3. 03AnimalAnimal study (in vivo)Mechanism

    In aged mice and rats, SS‑31 decreased opening of the mitochondrial permeability transition pore.

    In plain wordsIn aged mice and rats, SS‑31 reduced opening of the mitochondrial permeability transition pore.

    Peptide
    Elamipretide (SS-31)
    Outcome
    DecreaseMitochondrial permeability transition pore opening
    Study

    mice and ratsn: not reported in source

    naturally aging heart
    Outcome group
    Mitochondrial function · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    decreases the mitochondrial flash activity and mitochondrial permeability transition pore opening
    1 context sentence
    Summary · context
    Using the model of naturally aging mice and rats, we show direct evidence of increased proton leak in the aged heart mitochondria.
  4. 04AnimalAnimal study (in vivo)Mechanism

    In aged mice and rats, SS‑31 rejuvenated mitochondrial function by direct association with ANT1 and the mitochondrial ATP synthasome.

    In plain wordsIn aged mice and rats, SS‑31 restored mitochondrial function and bound directly to ANT1 and the ATP synthasome.

    Peptide
    Elamipretide (SS-31)
    Outcome
    Not applicableSS-31 association with ANT1 and ATP synthasome
    Study

    mice and ratsn: not reported in source

    naturally aging heart
    Outcome group
    Receptor activity and mechanism · Pharmacology
    Studied dose
    Dose not stated

    Source sentences

    Summary
    rejuvenates mitochondrial function by direct association with ANT1 and the mitochondrial ATP synthasome
    1 context sentence
    Summary · context
    Using the model of naturally aging mice and rats, we show direct evidence of increased proton leak in the aged heart mitochondria.
  5. 05AnimalAnimal study (in vivo)Efficacy outcome

    In aged mice and rats, SS‑31 led to substantial reversal of diastolic dysfunction.

    In plain wordsIn aged mice and rats, SS‑31 largely reversed the age-related diastolic dysfunction of the heart.

    Peptide
    Elamipretide (SS-31)
    Outcome
    DecreaseDiastolic dysfunction
    Study

    mice and ratsn: not reported in source

    naturally aging heart
    Outcome group
    Heart function · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    leads to substantial reversal of diastolic dysfunction.
    1 context sentence
    Summary · context
    Using the model of naturally aging mice and rats, we show direct evidence of increased proton leak in the aged heart mitochondria.

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.

  1. Version 2Current

    9 Oct 2026, 18:17 UTC

    Study results updated

  2. Version 1

    9 Oct 2026, 02:47 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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