Insights into the Biomarker Potential of Humanin and Mots-c Expression and Telomere Length in Alzheimer's Disease.

Rodríguez-Esparragón F, Cazorla-Rivero SE, Torrealba E, Cánovas-Molina Á, González-Hernández AN, Martín-Alfaro R, Afonso-Medina MP, Martínez de Saavedra-Álvarez MT, Pérez-Santana CG, Bartolomé C, Estupiñán L, González-Martín JM, Clavo B

International journal of molecular sciences9 Nov 2025

PMID41303353PMCIDPMC12652385DOI10.3390/ijms262210866PepBankPUB-41303353

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Summary

Humanin (HN) and MOTS-c are mitochondrial-derived peptides (MDPs) known for their neuroprotective and metabolic functions. Their circulating and tissue levels decline with age and in neurodegenerative diseases such as Alzheimer's disease (AD). This study aimed to evaluate whether blood and plasma gene expression and plasma protein levels of HN and MOTS-c are associated with AD markers, their role in the conversion from mild cognitive impairment (MCI) to AD, and their overall association with the disease. A case-control study was conducted, including patients with AD and MCI, and individuals with subjective cognitive decline (SCD) as controls. Gene expression levels were quantified from total RNA isolated from blood and plasma, normalised to mitochondrial DNA copy number (mtDNA-CN). ELISA was used to measure plasma HN and MOTS-c protein concentrations. HN and MOTS-c transcript levels differed significantly among study groups, whereas plasma protein concentrations did not discriminate between AD and MCI. In silico and RNA decay assays revealed faster degradation of HN mRNA and delayed but stable recovery of MOTS-c mRNA. Overall, blood and plasma transcript levels-but not circulating protein levels-of these MDPs were significantly reduced in AD compared to SCD, suggesting their potential as early biomarkers of Alzheimer's disease.

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

Results from this study8

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

Natural levels measured7

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 people with Alzheimer's disease, blood and plasma MOTS‑c transcript levels were significantly reduced compared with people with subjective cognitive decline.
In plain wordsIn people with Alzheimer's disease, activity of the body's own MOTS‑c gene was lower than in people with subjective cognitive decline.
Peptide
MOTS-c
Outcome
DecreaseBlood and plasma MOTS-c transcript levels, AD versus SCD
Study
n: not reported in source
Comparator
Subjective cognitive decline
Outcome group
Mitochondrial function · Nervous system and cognition
Source sentences
Summary
Overall, blood and plasma transcript levels-but not circulating protein levels-of these MDPs were significantly reduced in AD compared to SCD, suggesting their potential as early biomarkers of Alzheimer's disease.
1 context sentence(design, population, supporting numbers)
Summary · context
A case-control study was conducted, including patients with AD and MCI, and individuals with subjective cognitive decline (SCD) as controls.
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-4130335301
02HumanEndogenous levelObservational studyOther
In people with Alzheimer's disease, circulating MOTS‑c protein levels were not significantly reduced compared with people with subjective cognitive decline.
In plain wordsIn people with Alzheimer's disease, the body's own MOTS‑c protein level in blood was not clearly lower than in people with subjective cognitive decline.
Peptide
MOTS-c
Outcome
No significant changePlasma MOTS-c protein levels, AD versus SCD
Study
n: not reported in source
Comparator
Subjective cognitive decline
Outcome group
Mitochondrial function · Nervous system and cognition
Source sentences
Summary
Overall, blood and plasma transcript levels-but not circulating protein levels-of these MDPs were significantly reduced in AD compared to SCD, suggesting their potential as early biomarkers of Alzheimer's disease.
1 context sentence(design, population, supporting numbers)
Summary · context
A case-control study was conducted, including patients with AD and MCI, and individuals with subjective cognitive decline (SCD) as controls.
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-4130335302
03HumanEndogenous levelObservational studyOther
In people with Alzheimer's disease, plasma MOTS‑c protein concentrations did not discriminate AD from mild cognitive impairment.
In plain wordsIn people with Alzheimer's disease, the body's own MOTS‑c protein level in blood did not tell AD apart from mild cognitive impairment.
Peptide
MOTS-c
Outcome
No significant changePlasma MOTS-c protein, AD versus MCI
Study
n: not reported in source
Comparator
Mild cognitive impairment
Outcome group
Mitochondrial function · Nervous system and cognition
Source sentences
Summary
whereas plasma protein concentrations did not discriminate between AD and MCI.
1 context sentence(design, population, supporting numbers)
Summary · context
A case-control study was conducted, including patients with AD and MCI, and individuals with subjective cognitive decline (SCD) as controls.
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-4130335303
04HumanEndogenous levelObservational studyOther
In a case-control study, blood and plasma humanin transcript levels were significantly reduced in Alzheimer's disease compared with subjective cognitive decline.
In plain wordsIn people with Alzheimer's disease, the body's own humanin gene activity in blood was lower than in people with subjective cognitive decline.
Peptide
Humanin
Outcome
DecreaseBlood and plasma humanin transcript levels, AD versus SCD
Study
n: not reported in source
Comparator
Subjective cognitive decline
Outcome group
Endogenous peptide levels · Nervous system and cognition
Source sentences
Summary
Overall, blood and plasma transcript levels-but not circulating protein levels-of these MDPs were significantly reduced in AD compared to SCD, suggesting their potential as early biomarkers of Alzheimer's disease.
3 context sentences(design, population, supporting numbers)
Summary · context
HN and MOTS-c transcript levels differed significantly among study groups
Summary · context
A case-control study was conducted, including patients with AD and MCI, and individuals with subjective cognitive decline (SCD) as controls.
Summary · context
ELISA was used to measure plasma HN and MOTS-c protein concentrations.
This result measures the body's own Humanin. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-4130335305
05HumanEndogenous levelObservational studyOther
Plasma humanin protein concentrations did not discriminate between Alzheimer's disease and mild cognitive impairment.
In plain wordsNatural humanin protein levels in blood did not tell Alzheimer's disease apart from mild cognitive impairment.
Peptide
Humanin
Outcome
No significant changePlasma humanin protein, AD versus MCI
Study
n: not reported in source
Comparator
Mild cognitive impairment
Outcome group
Endogenous peptide levels · Nervous system and cognition
Source sentences
Summary
whereas plasma protein concentrations did not discriminate between AD and MCI.
2 context sentences(design, population, supporting numbers)
Summary · context
A case-control study was conducted, including patients with AD and MCI, and individuals with subjective cognitive decline (SCD) as controls.
Summary · context
ELISA was used to measure plasma HN and MOTS-c protein concentrations.
This result measures the body's own Humanin. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-4130335306
06HumanEndogenous levelObservational studyOther
Circulating humanin protein levels were not significantly reduced in Alzheimer's disease compared with subjective cognitive decline.
In plain wordsNatural humanin protein levels in blood were not lower in Alzheimer's disease than in subjective cognitive decline.
Peptide
Humanin
Outcome
No significant changeCirculating humanin protein, AD versus SCD
Study
n: not reported in source
Comparator
Subjective cognitive decline
Outcome group
Endogenous peptide levels · Nervous system and cognition
Source sentences
Summary
Overall, blood and plasma transcript levels-but not circulating protein levels-of these MDPs were significantly reduced in AD compared to SCD, suggesting their potential as early biomarkers of Alzheimer's disease.
2 context sentences(design, population, supporting numbers)
Summary · context
A case-control study was conducted, including patients with AD and MCI, and individuals with subjective cognitive decline (SCD) as controls.
Summary · context
ELISA was used to measure plasma HN and MOTS-c protein concentrations.
This result measures the body's own Humanin. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-4130335307
07LabEndogenous levelOther designMechanism
In in silico and RNA decay assays, humanin mRNA showed faster degradation, while MOTS-c mRNA showed delayed but stable recovery.
In plain wordsIn lab and computer tests, the body's own humanin messenger RNA broke down faster, while MOTS-c messenger RNA recovered later but stayed stable.
Peptide
Humanin
Outcome
Not applicableHumanin mRNA degradation rate
Study
n: not reported in source
Outcome group
Endogenous peptide levels · Nervous system and cognition
Source sentences
Summary
In silico and RNA decay assays revealed faster degradation of HN mRNA
This result measures the body's own Humanin. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-4130335308

Studies that did not test the peptide alone1

In this study, MOTS-c 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 MOTS-c.

08LabNot a test of MOTS-c aloneOther designMechanism
In RNA decay assays, MOTS‑c mRNA showed delayed but stable recovery.
In plain wordsIn lab tests, MOTS‑c messenger RNA showed delayed but stable recovery.
Peptide
MOTS-c
Outcome
Not applicableMOTS-c mRNA degradation kinetics
Study
n: not reported in source
RNA decay assays
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Source sentences
Summary
In silico and RNA decay assays revealed faster degradation of HN mRNA and delayed but stable recovery of MOTS-c mRNA.
In this study, MOTS-c 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 MOTS-c.
Show in the study text Report a problemFND-4130335304

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.

Versions 4 to 18Current
28 Oct 2026, 02:02 UTC
The same notice was added 15 times, first on 13 Oct 2026, 21:44 UTC. The status did not change between them.
Study results updated
Version 3
13 Oct 2026, 16:31 UTC
Study data updated · source update from Europe PMC
Version 2
10 Oct 2026, 08:19 UTC
Study results updated
Version 1
9 Oct 2026, 02:47 UTC
First added · source update from Europe PMC

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