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Study · Animal study (in vivo) · mouse · 2025

2 results

Age-related changes of skeletal muscle metabolic response to contraction are also sex-dependent.

Campbell MD, Djukovic D, Raftery D, Marcinek DJ

The Journal of physiology23 Sept 2023Cited by 14 (Europe PMC)

PMID37742081 (opens in a new tab)PMCIDPMC10959763 (opens in a new tab)DOI10.1113/jp285124 (opens in a new tab)PepBankPUB-37742081
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Summary

Mitochondria adapt to increased energy demands during muscle contraction by acutely altering metabolite fluxes and substrate oxidation. With age, an impaired mitochondrial metabolic response may contribute to reduced exercise tolerance and decreased skeletal muscle mass, specific force, increased overall fatty depositions in the skeletal muscle, frailty and depressed energy maintenance. We hypothesized that elevated energy stress in mitochondria with age alters the capacity of mitochondria to utilize different substrates following muscle contraction. To test this hypothesis, we used in vivo electrical stimulation to simulate high-intensity intervals (HII) or low intensity steady-state (LISS) exercise in young (5-7 months) and aged (27-29 months) male and female mice to characterize effects of age and sex on mitochondrial substrate utilization in skeletal muscle following contraction. Mitochondrial respiration using glutamate decreased in aged males following HII and glutamate oxidation was inhibited following HII in both the contracted and non-stimulated muscle of aged female muscle. Analyses of the muscle metabolome of female mice indicated that changes in metabolic pathways induced by HII and LISS contractions in young muscle are absent in aged muscle. To test improved mitochondrial function on substrate utilization following HII, we treated aged females with elamipretide (ELAM), a mitochondrially-targeted peptide shown to improve mitochondrial bioenergetics and restore redox status in aged muscle. ELAM removed inhibition of glutamate oxidation and showed increased metabolic pathway changes following HII, suggesting rescuing redox status and improving bioenergetic function in mitochondria from aged muscle increases glutamate utilization and enhances the metabolic response to muscle contraction in aged muscle. KEY POINTS: Acute local contraction of gastrocnemius can systemically alter mitochondrial respiration in non-stimulated muscle. Age-related changes in mitochondrial respiration using glutamate or palmitoyl carnitine following contraction are sex-dependent. Respiration using glutamate after high-intensity contraction is inhibited in aged female muscle. Metabolite level and pathway changes following muscle contraction decrease with age in female mice. Treatment with the mitochondrially-targeted peptide elamipretide can partially rescue metabolite response to muscle contraction.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study2

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

  1. 01AnimalAnimal study (in vivo)Mechanism

    In aged female mice, elamipretide removed the inhibition of glutamate oxidation after high-intensity contraction.

    In plain wordsIn aged female mice, elamipretide restored muscle cells' ability to use glutamate after intense contraction.

    Peptide
    Elamipretide (SS-31)
    Outcome
    IncreaseGlutamate oxidation after high-intensity contraction
    Study

    mousen: not reported in source

    aged female mice, in vivo electrical stimulation (HII)
    Outcome group
    Mitochondrial function · Musculoskeletal
    Studied dose
    Dose not stated

    Source sentences

    Summary
    ELAM removed inhibition of glutamate oxidation and showed increased metabolic pathway changes following HII
    2 context sentences
    Summary · context
    To test this hypothesis, we used in vivo electrical stimulation to simulate high-intensity intervals (HII) or low intensity steady-state (LISS) exercise in young (5-7 months) and aged (27-29 months) male and female mice to characterize effects of age and sex on mitochondrial substrate utilization in skeletal muscle following contraction.
    Summary · context
    To test improved mitochondrial function on substrate utilization following HII, we treated aged females with elamipretide (ELAM), a mitochondrially-targeted peptide shown to improve mitochondrial bioenergetics and restore redox status in aged muscle.
  2. 02AnimalAnimal study (in vivo)Mechanism

    In aged female mice, elamipretide increased metabolic pathway changes after high-intensity contraction.

    In plain wordsIn aged female mice, elamipretide increased the muscle's metabolic response to intense contraction.

    Peptide
    Elamipretide (SS-31)
    Outcome
    IncreaseMetabolic pathway changes after high-intensity contraction
    Study

    mousen: not reported in source

    aged female mice, in vivo electrical stimulation (HII)
    Outcome group
    Mitochondrial function · Musculoskeletal
    Studied dose
    Dose not stated

    Source sentences

    Summary
    ELAM removed inhibition of glutamate oxidation and showed increased metabolic pathway changes following HII
    2 context sentences
    Summary · context
    To test this hypothesis, we used in vivo electrical stimulation to simulate high-intensity intervals (HII) or low intensity steady-state (LISS) exercise in young (5-7 months) and aged (27-29 months) male and female mice to characterize effects of age and sex on mitochondrial substrate utilization in skeletal muscle following contraction.
    Summary · context
    To test improved mitochondrial function on substrate utilization following HII, we treated aged females with elamipretide (ELAM), a mitochondrially-targeted peptide shown to improve mitochondrial bioenergetics and restore redox status in aged muscle.

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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