Increased expression of the mitochondrial derived peptide, MOTS-c, in skeletal muscle of healthy aging men is associated with myofiber composition.

D'Souza RF, Woodhead JST, Hedges CP, Zeng N, Wan J, Kumagai H, Lee C, Cohen P, Cameron-Smith D, Mitchell CJ, Merry TL

Aging17 Mar 2020Cited by 50 (Europe PMC)

PMID32182209PMCIDPMC7138593DOI10.18632/aging.102944PepBankPUB-32182209

Summary

Mitochondria putatively regulate the aging process, in part, through the small regulatory peptide, mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) that is encoded by the mitochondrial genome. Here we investigated the regulation of MOTS-c in the plasma and skeletal muscle of healthy aging men. Circulating MOTS-c reduced with age, but older (70-81 y) and middle-aged (45-55 y) men had ~1.5-fold higher skeletal muscle MOTS-c expression than young (18-30 y). Plasma MOTS-c levels only correlated with plasma in young men, was associated with markers of slow-type muscle, and associated with improved muscle quality in the older group (maximal leg-press load relative to thigh cross-sectional area). Using small mRNA assays we provide evidence that MOTS-c transcription may be regulated independently of the full length 12S rRNA gene in which it is encoded, and expression is not associated with antioxidant response element (ARE)-related genes as previously seen in culture. Our results suggest that plasma and muscle MOTS-c are differentially regulated with aging, and the increase in muscle MOTS-c expression with age is consistent with fast-to-slow type muscle fiber transition. Further research is required to determine the molecular targets of endogenous MOTS-c in human muscle but they may relate to factors that maintain muscle quality.

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

Results from this study6

No result from this study comes from a test of the peptide.

Natural levels measured6

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.

01HumanEndogenous levelObservational studyOther
In healthy men, circulating MOTS‑c fell with age.
In plain wordsIn healthy men, the body's own MOTS‑c level in blood was lower with older age.
Peptide
MOTS-c
Outcome
DecreaseCirculating MOTS-c with age
Study
n: not reported in source
Outcome group
Aging markers · Aging and longevity
Source sentences
Summary
Circulating MOTS-c reduced with age
1 context sentence(design, population, supporting numbers)
Summary · context
Here we investigated the regulation of MOTS-c in the plasma and skeletal muscle of healthy aging men.
This result measures the body's own MOTS-c. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-3218220901
02HumanEndogenous levelObservational studyOther
Older (70-81 y) and middle-aged (45-55 y) men had about 1.5-fold higher skeletal muscle MOTS‑c expression than young men (18-30 y).
In plain wordsOlder and middle-aged men had higher natural MOTS‑c in their muscle than young men.
Peptide
MOTS-c
Outcome
IncreaseSkeletal muscle MOTS-c expression in older and middle-aged versus young men
Study
n: not reported in source
Comparator
Young men (18-30 y)
Outcome group
Aging markers · Musculoskeletal
Measurements
Muscle MOTS-c expression vs young
≈ 1.5 fold
older and middle-aged men
Source sentences
Summary
older (70-81 y) and middle-aged (45-55 y) men had ~1.5-fold higher skeletal muscle MOTS-c expression than young (18-30 y)
1 context sentence(design, population, supporting numbers)
Summary · context
Here we investigated the regulation of MOTS-c in the plasma and skeletal muscle of healthy aging men.
This result measures the body's own MOTS-c. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-3218220902
03HumanEndogenous levelObservational studyOther
MOTS‑c was associated with markers of slow-type muscle.
In plain wordsNatural MOTS‑c levels were linked to markers of slow-type muscle fibres.
Peptide
MOTS-c
Outcome
Not applicableAssociation of MOTS-c with markers of slow-type muscle
Study
n: not reported in source
Outcome group
Exercise and physical function · Musculoskeletal
Source sentences
Summary
was associated with markers of slow-type muscle
1 context sentence(design, population, supporting numbers)
Summary · context
Here we investigated the regulation of MOTS-c in the plasma and skeletal muscle of healthy aging men.
This result measures the body's own MOTS-c. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-3218220903
04HumanEndogenous levelObservational studyOther
In older men, plasma MOTS‑c was associated with improved muscle quality (maximal leg-press load relative to thigh cross-sectional area).
In plain wordsIn older men, the body's own MOTS‑c level was linked to better muscle quality.
Peptide
MOTS-c
Outcome
Not applicableAssociation of MOTS-c with muscle quality in older men
Study
n: not reported in source
Outcome group
Exercise and physical function · Musculoskeletal
Source sentences
Summary
associated with improved muscle quality in the older group (maximal leg-press load relative to thigh cross-sectional area).
1 context sentence(design, population, supporting numbers)
Summary · context
Here we investigated the regulation of MOTS-c in the plasma and skeletal muscle of healthy aging men.
This result measures the body's own MOTS-c. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-3218220904
05HumanEndogenous levelObservational studyOther
MOTS‑c expression in muscle was not associated with antioxidant response element (ARE)-related genes.
In plain wordsNatural MOTS‑c in muscle was not linked to antioxidant response genes.
Peptide
MOTS-c
Outcome
No significant changeAssociation of MOTS-c expression with antioxidant response element-related genes
Study
n: not reported in source
Outcome group
Aging markers · Musculoskeletal
Source sentences
Summary
expression is not associated with antioxidant response element (ARE)-related genes as previously seen in culture.
1 context sentence(design, population, supporting numbers)
Summary · context
Here we investigated the regulation of MOTS-c in the plasma and skeletal muscle of healthy aging men.
This result measures the body's own MOTS-c. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-3218220905
06HumanEndogenous levelObservational studyMechanism
Small mRNA assays gave evidence that MOTS‑c transcription may be regulated independently of the full-length 12S rRNA gene that encodes it.
In plain wordsTests suggested that natural MOTS‑c may be controlled separately from the gene that contains it.
Peptide
MOTS-c
Outcome
Not applicableIndependent regulation of MOTS-c transcription from the 12S rRNA gene
Study
n: not reported in source
Outcome group
Receptor activity and mechanism · Musculoskeletal
Source sentences
Summary
Using small mRNA assays we provide evidence that MOTS-c transcription may be regulated independently of the full length 12S rRNA gene in which it is encoded
1 context sentence(design, population, supporting numbers)
Summary · context
Here we investigated the regulation of MOTS-c in the plasma and skeletal muscle of healthy aging men.
This result measures the body's own MOTS-c. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-3218220906

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
10 Oct 2026, 08:19 UTC
Study results updated
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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