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

8 results

Late-life restoration of mitochondrial function reverses cardiac dysfunction in old mice.

Chiao YA, Zhang H, Sweetwyne M, Whitson J, Ting YS, Basisty N, Pino LK, Quarles E, Nguyen NH, Campbell MD, Campbell MD, Zhang T and 11 more

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Gaffrey MJ, Merrihew G, Wang L, Yue Y, Duan D, Granzier HL, Szeto HH, Qian WJ, Marcinek D, MacCoss MJ, Rabinovitch P

eLife10 Jul 2020Cited by 118 (Europe PMC)

Summary

Diastolic dysfunction is a prominent feature of cardiac aging in both mice and humans. We show here that 8-week treatment of old mice with the mitochondrial targeted peptide SS-31 (elamipretide) can substantially reverse this deficit. SS-31 normalized the increase in proton leak and reduced mitochondrial ROS in cardiomyocytes from old mice, accompanied by reduced protein oxidation and a shift towards a more reduced protein thiol redox state in old hearts. Improved diastolic function was concordant with increased phosphorylation of cMyBP-C Ser282 but was independent of titin isoform shift. Late-life viral expression of mitochondrial-targeted catalase (mCAT) produced similar functional benefits in old mice and SS-31 did not improve cardiac function of old mCAT mice, implicating normalizing mitochondrial oxidative stress as an overlapping mechanism. These results demonstrate that pre-existing cardiac aging phenotypes can be reversed by targeting mitochondrial dysfunction and implicate mitochondrial energetics and redox signaling as therapeutic targets for cardiac aging.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study8

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

  1. 01AnimalAnimal study (in vivo)Efficacy outcome

    In old mice, 8 weeks of SS‑31 treatment substantially reversed the diastolic dysfunction of cardiac aging.

    In plain wordsIn old mice, 8 weeks of SS‑31 largely reversed age-related problems with the heart relaxing between beats.

    Outcome
    IncreaseDiastolic function
    Study

    mousen: not reported in source

    old mice (cardiac aging)
    Outcome group
    Heart function · Cardiovascular
    Studied dose
    Dose not stated · 8 weeksAs given in this study (mouse).

    Source sentences

    Summary
    We show here that 8-week treatment of old mice with the mitochondrial targeted peptide SS-31 (elamipretide) can substantially reverse this deficit.
  2. 02AnimalAnimal study (in vivo)Mechanism

    In cardiomyocytes from old mice, SS‑31 normalized the increased proton leak.

    In plain wordsIn old mice, SS‑31 brought the raised mitochondrial proton leak in heart cells back toward normal.

    Outcome
    DecreaseMitochondrial proton leak in cardiomyocytes
    Study

    mousen: not reported in source

    old mice (cardiac aging)
    Outcome group
    Mitochondrial function · Cardiovascular
    Studied dose
    Dose not stated · 8 weeksAs given in this study (mouse).

    Source sentences

    Summary
    SS-31 normalized the increase in proton leak
    1 context sentence
    Summary · context
    We show here that 8-week treatment of old mice with the mitochondrial targeted peptide SS-31 (elamipretide) can substantially reverse this deficit.
  3. 03AnimalAnimal study (in vivo)Mechanism

    In cardiomyocytes from old mice, SS‑31 reduced mitochondrial reactive oxygen species.

    In plain wordsIn old mice, SS‑31 lowered reactive oxygen species made by mitochondria in heart cells.

    Outcome
    DecreaseMitochondrial ROS in cardiomyocytes
    Study

    mousen: not reported in source

    old mice (cardiac aging)
    Outcome group
    Mitochondrial function · Cardiovascular
    Studied dose
    Dose not stated · 8 weeksAs given in this study (mouse).

    Source sentences

    Summary
    reduced mitochondrial ROS in cardiomyocytes from old mice, accompanied by reduced protein oxidation and a shift towards a more reduced protein thiol redox state in old hearts.
    1 context sentence
    Summary · context
    We show here that 8-week treatment of old mice with the mitochondrial targeted peptide SS-31 (elamipretide) can substantially reverse this deficit.
  4. 04AnimalAnimal study (in vivo)Mechanism

    In old mouse hearts, SS‑31 reduced protein oxidation.

    In plain wordsIn old mice, SS‑31 reduced oxidative damage to proteins in the heart.

    Outcome
    DecreaseProtein oxidation in old hearts
    Study

    mousen: not reported in source

    old mice (cardiac aging)
    Outcome group
    Mitochondrial function · Cardiovascular
    Studied dose
    Dose not stated · 8 weeksAs given in this study (mouse).

    Source sentences

    Summary
    accompanied by reduced protein oxidation and a shift towards a more reduced protein thiol redox state in old hearts.
    1 context sentence
    Summary · context
    We show here that 8-week treatment of old mice with the mitochondrial targeted peptide SS-31 (elamipretide) can substantially reverse this deficit.
  5. 05AnimalAnimal study (in vivo)Mechanism

    In old mouse hearts, SS‑31 shifted the protein thiol redox state towards a more reduced state.

    In plain wordsIn old mice, SS‑31 moved the heart's protein redox balance towards a more reduced state.

    Outcome
    MixedProtein thiol redox state in old hearts
    Study

    mousen: not reported in source

    old mice (cardiac aging)
    Outcome group
    Mitochondrial function · Cardiovascular
    Studied dose
    Dose not stated · 8 weeksAs given in this study (mouse).

    Source sentences

    Summary
    a shift towards a more reduced protein thiol redox state in old hearts.
    1 context sentence
    Summary · context
    We show here that 8-week treatment of old mice with the mitochondrial targeted peptide SS-31 (elamipretide) can substantially reverse this deficit.
  6. 06AnimalAnimal study (in vivo)Mechanism

    In old mice, improved diastolic function with SS‑31 was concordant with increased phosphorylation of cMyBP-C Ser282.

    In plain wordsIn old mice, better heart relaxation with SS‑31 came with more phosphorylation of a heart muscle protein.

    Outcome
    IncreasecMyBP-C Ser282 phosphorylation
    Study

    mousen: not reported in source

    old mice (cardiac aging)
    Outcome group
    Heart function · Cardiovascular
    Studied dose
    Dose not stated · 8 weeksAs given in this study (mouse).

    Source sentences

    Summary
    Improved diastolic function was concordant with increased phosphorylation of cMyBP-C Ser282
    1 context sentence
    Summary · context
    We show here that 8-week treatment of old mice with the mitochondrial targeted peptide SS-31 (elamipretide) can substantially reverse this deficit.
  7. 07AnimalAnimal study (in vivo)Mechanism

    In old mice, the improved diastolic function with SS‑31 was independent of titin isoform shift.

    In plain wordsIn old mice, the heart benefit of SS‑31 did not depend on a change in titin protein form.

    Outcome
    No significant changeTitin isoform shift
    Study

    mousen: not reported in source

    old mice (cardiac aging)
    Outcome group
    Heart function · Cardiovascular
    Studied dose
    Dose not stated · 8 weeksAs given in this study (mouse).

    Source sentences

    Summary
    but was independent of titin isoform shift.
    1 context sentence
    Summary · context
    We show here that 8-week treatment of old mice with the mitochondrial targeted peptide SS-31 (elamipretide) can substantially reverse this deficit.
  8. 08AnimalAnimal study (in vivo)Efficacy outcome

    In old mice expressing mitochondrial-targeted catalase, SS‑31 did not improve cardiac function.

    In plain wordsIn old mice that already had a mitochondria-targeted catalase, SS‑31 did not improve heart function.

    Outcome
    No significant changeCardiac function in old mCAT mice
    Study

    mousen: not reported in source

    old mCAT mice
    Outcome group
    Heart function · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    SS-31 did not improve cardiac function of old mCAT mice
    1 context sentence
    Summary · context
    We show here that 8-week treatment of old mice with the mitochondrial targeted peptide SS-31 (elamipretide) can substantially reverse this deficit.

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

    10 Oct 2026, 08:19 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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