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Study · Animal study (in vivo) · mouse · 2021

7 results

MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis.

Reynolds JC, Lai RW, Woodhead JST, Joly JH, Mitchell CJ, Cameron-Smith D, Lu R, Cohen P, Graham NA, Benayoun BA, Merry TL, Lee C

Nature communications20 Jan 2021Cited by 175 (Europe PMC)

PMID33473109 (opens in a new tab)PMCIDPMC7817689 (opens in a new tab)DOI10.1038/s41467-020-20790-0 (opens in a new tab)PepBankPUB-33473109
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Summary

Healthy aging can be promoted by enhanced metabolic fitness and physical capacity. Mitochondria are chief metabolic organelles with strong implications in aging that also coordinate broad physiological functions, in part, using peptides that are encoded within their independent genome. However, mitochondrial-encoded factors that actively regulate aging are unknown. Here, we report that mitochondrial-encoded MOTS-c can significantly enhance physical performance in young (2 mo.), middle-age (12 mo.), and old (22 mo.) mice. MOTS-c can regulate (i) nuclear genes, including those related to metabolism and proteostasis, (ii) skeletal muscle metabolism, and (iii) myoblast adaptation to metabolic stress. We provide evidence that late-life (23.5 mo.) initiated intermittent MOTS-c treatment (3x/week) can increase physical capacity and healthspan in mice. In humans, exercise induces endogenous MOTS-c expression in skeletal muscle and in circulation. Our data indicate that aging is regulated by genes encoded in both of our co-evolved mitochondrial and nuclear genomes.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study7

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

  1. 01AnimalAnimal study (in vivo)Efficacy outcome

    MOTS‑c significantly enhanced physical performance in young (2 months), middle-age (12 months) and old (22 months) mice.

    In plain wordsIn mice of three ages, MOTS‑c improved physical performance.

    Peptide
    MOTS-c
    Outcome
    IncreasePhysical performance in young, middle-age and old mice
    Study

    mousen: not reported in source

    Outcome group
    Exercise and physical function · Aging and longevity
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Here, we report that mitochondrial-encoded MOTS-c can significantly enhance physical performance in young (2 mo.), middle-age (12 mo.), and old (22 mo.) mice.
  2. 02AnimalAnimal study (in vivo)Efficacy outcome

    In mice, late-life (23.5 months) intermittent MOTS‑c treatment (3 times per week) increased physical capacity.

    In plain wordsIn old mice, MOTS‑c given three times a week late in life increased physical capacity.

    Peptide
    MOTS-c
    Outcome
    IncreasePhysical capacity with late-life intermittent treatment
    Study

    mousen: not reported in source

    Outcome group
    Exercise and physical function · Aging and longevity
    Studied dose
    Dose not stated · 3x/week from 23.5 months of ageAs given in this study (mouse).

    Source sentences

    Summary
    We provide evidence that late-life (23.5 mo.) initiated intermittent MOTS-c treatment (3x/week) can increase physical capacity and healthspan in mice.
  3. 03AnimalAnimal study (in vivo)Efficacy outcome

    In mice, late-life (23.5 months) intermittent MOTS‑c treatment (3 times per week) increased healthspan.

    In plain wordsIn old mice, MOTS‑c given three times a week late in life extended healthspan.

    Peptide
    MOTS-c
    Outcome
    IncreaseHealthspan with late-life intermittent treatment
    Study

    mousen: not reported in source

    Outcome group
    Aging markers · Aging and longevity
    Studied dose
    Dose not stated · 3x/week from 23.5 months of ageAs given in this study (mouse).

    Source sentences

    Summary
    We provide evidence that late-life (23.5 mo.) initiated intermittent MOTS-c treatment (3x/week) can increase physical capacity and healthspan in mice.
  4. 04AnimalOther designMechanism

    MOTS‑c regulated nuclear genes, including those related to metabolism and proteostasis.

    In plain wordsMOTS‑c changed the activity of nuclear genes linked to metabolism and protein quality control.

    Peptide
    MOTS-c
    Outcome
    Not applicableRegulation of nuclear genes
    Study

    n: not reported in source

    Outcome group
    Receptor activity and mechanism · Aging and longevity
    Studied dose
    Dose not stated

    Source sentences

    Summary
    MOTS-c can regulate (i) nuclear genes, including those related to metabolism and proteostasis
  5. 05AnimalOther designMechanism

    MOTS‑c regulated skeletal muscle metabolism.

    In plain wordsMOTS‑c changed how skeletal muscle handles energy.

    Peptide
    MOTS-c
    Outcome
    Not applicableSkeletal muscle metabolism
    Study

    n: not reported in source

    Outcome group
    Mitochondrial function · Musculoskeletal
    Studied dose
    Dose not stated

    Source sentences

    Summary
    (ii) skeletal muscle metabolism, and (iii) myoblast adaptation to metabolic stress.
  6. 06LabIn vitro (cells)Mechanism

    MOTS‑c regulated myoblast adaptation to metabolic stress.

    In plain wordsMOTS‑c changed how muscle precursor cells adapt to metabolic stress.

    Peptide
    MOTS-c
    Outcome
    Not applicableMyoblast adaptation to metabolic stress
    Study

    n: not reported in source

    Outcome group
    Mitochondrial function · Musculoskeletal
    Studied dose
    Dose not stated

    Source sentences

    Summary
    (iii) myoblast adaptation to metabolic stress.

Natural levels measured1

These results measure the body's own peptide. Nobody was given the peptide. They are not evidence about taking it. They are left out of key results, evidence counts and charts.

  1. 07HumanEndogenous levelOther designOther

    In humans, exercise increased the body's own MOTS‑c expression in skeletal muscle and in circulation.

    In plain wordsIn people, exercise raised the body's own MOTS‑c in muscle and blood.

    Peptide
    MOTS-c
    Outcome
    IncreaseEndogenous MOTS-c expression after exercise
    Study

    n: not reported in source

    Outcome group
    Exercise and physical function · Metabolic and weight

    Source sentences

    Summary
    In humans, exercise induces endogenous MOTS-c expression in skeletal muscle and in circulation.

    This result measures the body's own MOTS-c. Nobody was given the peptide. It is not evidence about taking it.

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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