SS-31 and NMN: Two paths to improve metabolism and function in aged hearts.

Whitson JA, Bitto A, Zhang H, Sweetwyne MT, Coig R, Bhayana S, Shankland EG, Wang L, Bammler TK, Mills KF, Imai SI, Conley KE, Marcinek DJ, Rabinovitch PS

Aging cell11 Aug 2020Cited by 57 (Europe PMC)

PMID32779818PMCIDPMC7576234DOI10.1111/acel.13213PepBankPUB-32779818

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Summary

The effects of two different mitochondrial-targeted drugs, SS-31 and NMN, were tested on Old mouse hearts. After treatment with the drugs, individually or Combined, heart function was examined by echocardiography. SS-31 partially reversed an age-related decline in diastolic function while NMN fully reversed an age-related deficiency in systolic function at a higher workload. Metabolomic analysis revealed that both NMN and the Combined treatment increased nicotinamide and 1-methylnicotinamide levels, indicating greater NAD⁺ turnover, but only the Combined treatment resulted in significantly greater steady-state NAD(H) levels. A novel magnetic resonance spectroscopy approach was used to assess how metabolite levels responded to changing cardiac workload. PCr/ATP decreased in response to increased workload in Old Control, but not Young, hearts, indicating an age-related decline in energetic capacity. Both drugs were able to normalize the PCr/ATP dynamics. SS-31 and NMN treatment also increased mitochondrial NAD(P)H production under the higher workload, while only NMN increased NAD⁺ in response to increased work. These measures did not shift in hearts given the Combined treatment, which may be owed to the enhanced NAD(H) levels in the resting state after this treatment. Overall, these results indicate that both drugs are effective at restoring different aspects of mitochondrial and heart health and that combining them results in a synergistic effect that rejuvenates Old hearts and best recapitulates the Young state.

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

Results from this study8

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

01AnimalAnimal study (in vivo)Efficacy outcome
In old mice, SS‑31 partially reversed the age-related decline in diastolic function measured by echocardiography.
In plain wordsIn old mice, SS‑31 partly reversed the age-related decline in how well the heart relaxes.
Peptide
Elamipretide (SS-31)
Outcome
IncreaseAge-related decline in diastolic function
Study
mousen: not reported in source
old mouse hearts
Outcome group
Heart function · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
SS-31 partially reversed an age-related decline in diastolic function
1 context sentence(design, population, supporting numbers)
Summary · context
The effects of two different mitochondrial-targeted drugs, SS-31 and NMN, were tested on Old mouse hearts.
Show in the study text Report a problemFND-3277981801
02AnimalAnimal study (in vivo)Mechanism
In old mouse hearts, SS‑31 normalized the PCr/ATP response to increased workload, which was abnormal in old control hearts.
In plain wordsIn old mice, SS‑31 brought the heart's energy-reserve response to higher workload back toward normal.
Peptide
Elamipretide (SS-31)
Outcome
Not applicablePCr/ATP dynamics under increased workload
Study
mousen: not reported in source
old mouse hearts
Outcome group
Mitochondrial function · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
PCr/ATP decreased in response to increased workload in Old Control, but not Young, hearts, indicating an age-related decline in energetic capacity. Both drugs were able to normalize the PCr/ATP dynamics.
1 context sentence(design, population, supporting numbers)
Summary · context
The effects of two different mitochondrial-targeted drugs, SS-31 and NMN, were tested on Old mouse hearts.
Show in the study text Report a problemFND-3277981802
03AnimalAnimal study (in vivo)Mechanism
In old mouse hearts, SS‑31 increased mitochondrial NAD(P)H production under the higher workload.
In plain wordsIn old mice, SS‑31 raised mitochondrial NAD(P)H production in the heart under higher workload.
Peptide
Elamipretide (SS-31)
Outcome
IncreaseMitochondrial NAD(P)H production under higher workload
Study
mousen: not reported in source
old mouse hearts
Outcome group
Mitochondrial function · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
SS-31 and NMN treatment also increased mitochondrial NAD(P)H production under the higher workload
1 context sentence(design, population, supporting numbers)
Summary · context
The effects of two different mitochondrial-targeted drugs, SS-31 and NMN, were tested on Old mouse hearts.
Show in the study text Report a problemFND-3277981803
04AnimalAnimal study (in vivo)Mechanism
In old mouse hearts, SS‑31 did not increase NAD+ in response to increased work; only NMN did.
In plain wordsIn old mice, SS‑31 did not raise heart NAD+ with higher work; only NMN did.
Peptide
Elamipretide (SS-31)
Outcome
No significant changeNAD+ response to increased work
Study
mousen: not reported in source
old mouse hearts
Outcome group
Mitochondrial function · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
while only NMN increased NAD⁺ in response to increased work.
1 context sentence(design, population, supporting numbers)
Summary · context
The effects of two different mitochondrial-targeted drugs, SS-31 and NMN, were tested on Old mouse hearts.
Show in the study text Report a problemFND-3277981804
05AnimalAnimal study (in vivo)Mechanism
In old mouse hearts, only the combined SS‑31 and NMN treatment significantly increased steady-state NAD(H) levels.
In plain wordsIn old mice, only SS‑31 combined with NMN, not either drug alone, raised resting heart NAD(H) levels.
Peptide
Elamipretide (SS-31)
Outcome
IncreaseSteady-state NAD(H) levels with combined SS-31 and NMN
Study
mousen: not reported in source
old mouse hearts
Outcome group
Mitochondrial function · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
only the Combined treatment resulted in significantly greater steady-state NAD(H) levels.
1 context sentence(design, population, supporting numbers)
Summary · context
The effects of two different mitochondrial-targeted drugs, SS-31 and NMN, were tested on Old mouse hearts.
Show in the study text Report a problemFND-3277981806

Studies that did not test the peptide alone3

In this study, Elamipretide (SS-31) was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Elamipretide (SS-31).

06AnimalNot a test of Elamipretide (SS-31) aloneAnimal study (in vivo)Mechanism
In old mouse hearts, combined SS‑31 and NMN treatment increased nicotinamide and 1-methylnicotinamide levels, indicating greater NAD+ turnover; NMN alone did the same.
In plain wordsIn old mice, SS‑31 plus NMN raised markers of NAD+ turnover in the heart; NMN alone had the same effect.
Peptide
Elamipretide (SS-31)
Outcome
IncreaseNicotinamide and 1-methylnicotinamide levels with combined SS-31 and NMN
Study
mousen: not reported in source
old mouse hearts
Outcome group
Mitochondrial function · Cardiovascular
Source sentences
Summary
both NMN and the Combined treatment increased nicotinamide and 1-methylnicotinamide levels, indicating greater NAD⁺ turnover
1 context sentence(design, population, supporting numbers)
Summary · context
The effects of two different mitochondrial-targeted drugs, SS-31 and NMN, were tested on Old mouse hearts.
In this study, Elamipretide (SS-31) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Elamipretide (SS-31).
Show in the study text Report a problemFND-3277981805
07AnimalNot a test of Elamipretide (SS-31) aloneAnimal study (in vivo)Mechanism
In old mouse hearts, the NAD(P)H response to higher workload did not shift with combined SS‑31 and NMN treatment.
In plain wordsIn old mice, the heart NAD(P)H response to higher workload did not change after SS‑31 plus NMN.
Peptide
Elamipretide (SS-31)
Outcome
No significant changeWorkload-induced NAD(P)H response with combined SS-31 and NMN
Study
mousen: not reported in source
old mouse hearts
Outcome group
Mitochondrial function · Cardiovascular
Source sentences
Summary
These measures did not shift in hearts given the Combined treatment, which may be owed to the enhanced NAD(H) levels in the resting state after this treatment.
1 context sentence(design, population, supporting numbers)
Summary · context
The effects of two different mitochondrial-targeted drugs, SS-31 and NMN, were tested on Old mouse hearts.
In this study, Elamipretide (SS-31) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Elamipretide (SS-31).
Show in the study text Report a problemFND-3277981807
08AnimalNot a test of Elamipretide (SS-31) aloneAnimal study (in vivo)Mechanism
In old mouse hearts, the NAD+ response to higher workload did not shift with combined SS‑31 and NMN treatment.
In plain wordsIn old mice, the heart NAD+ response to higher workload did not change after SS‑31 plus NMN.
Peptide
Elamipretide (SS-31)
Outcome
No significant changeWorkload-induced NAD+ response with combined SS-31 and NMN
Study
mousen: not reported in source
old mouse hearts
Outcome group
Mitochondrial function · Cardiovascular
Source sentences
Summary
These measures did not shift in hearts given the Combined treatment, which may be owed to the enhanced NAD(H) levels in the resting state after this treatment.
1 context sentence(design, population, supporting numbers)
Summary · context
The effects of two different mitochondrial-targeted drugs, SS-31 and NMN, were tested on Old mouse hearts.
In this study, Elamipretide (SS-31) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Elamipretide (SS-31).
Show in the study text Report a problemFND-3277981808

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
9 Oct 2026, 18:17 UTC
Study results updated
Version 1
9 Oct 2026, 02:47 UTC
First added · source update from Europe PMC

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