Characterization of the Effects of a Humanin Fragment Peptide (HNF₁₄) in Age-Related Macular Degeneration.

Nashine S, Kenney MC

Journal of clinical medicine24 Feb 2026

PMID41827105PMCIDPMC12985917DOI10.3390/jcm15051686PepBankPUB-41827105

Summary

Background: Age-related macular degeneration (AMD) is a leading cause of vision loss and is strongly associated with mitochondrial dysfunction in retinal pigment epithelial cells. Mitochondrial-derived peptides, including Humanin and its analogs, have demonstrated cytoprotective effects in AMD-related cellular models. However, the effects of shorter Humanin-derived fragments in disease-specific mitochondrial models remain incompletely characterized. Methods: Transmitochondrial retinal pigment epithelial cybrid cell lines containing mitochondria from AMD patients or age-matched normal donors were treated with HNF₁₄, a 14-amino acid Humanin fragment peptide. Cellular metabolic activity, cytotoxicity, oxidative stress, apoptotic signaling, inflammatory markers, angiogenic factor expression, and amyloid-β_1-42-induced apoptosis were evaluated using biochemical assays, protein analyses, and live-cell imaging approaches. Results: HNF₁₄ treatment was associated with improved metabolic activity and reduced cytotoxicity in AMD cybrids, with minimal effects in normal cybrids. HNF₁₄ significantly reduced intracellular and mitochondrial oxidative stress, suppressed apoptotic and inflammatory markers, and decreased VEGF-A protein expression in AMD cybrids. In addition, HNF₁₄ attenuated amyloid-β_1-42-induced apoptotic signaling in AMD cybrids. These effects were selective for cybrids containing AMD-derived mitochondria. Conclusions: This study demonstrates that HNF₁₄ mitigates mitochondrial and cellular stress responses in AMD transmitochondrial cybrid cells. The findings indicate that a short Humanin-derived fragment retains cytoprotective activity in a disease-specific mitochondrial context and support further investigation of mitochondrial-derived peptides as modulators of mitochondrial dysfunction relevant to AMD pathophysiology.

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

Results from this study9

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

Studies that did not test the peptide alone9

In this study, Humanin 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 Humanin.

01LabNot a test of Humanin aloneIn vitro (cells)Efficacy outcome
In AMD cybrid cells, treatment with the humanin fragment HNF14 was associated with improved metabolic activity.
In plain wordsIn cells, a short humanin fragment was linked to better metabolic activity in cells carrying AMD-type mitochondria.
Peptide
Humanin
Outcome
IncreaseCellular metabolic activity in AMD cybrids
Study
humann: not reported in source
Transmitochondrial retinal pigment epithelial cybrid cells with AMD or normal mitochondria
Comparator
Untreated cybrids
Outcome group
Mitochondrial function · Eye
Source sentences
Summary
HNF₁₄ treatment was associated with improved metabolic activity
1 context sentence(design, population, supporting numbers)
Summary · context
Transmitochondrial retinal pigment epithelial cybrid cell lines containing mitochondria from AMD patients or age-matched normal donors were treated with HNF₁₄, a 14-amino acid Humanin fragment peptide.
In this study, Humanin 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 Humanin.
Show in the study text Report a problemFND-4182710501
02LabNot a test of Humanin aloneIn vitro (cells)Efficacy outcome
In AMD cybrid cells, treatment with the humanin fragment HNF14 was associated with reduced cytotoxicity.
In plain wordsIn cells, a short humanin fragment was linked to less cell damage in cells carrying AMD-type mitochondria.
Peptide
Humanin
Outcome
DecreaseCytotoxicity in AMD cybrids
Study
humann: not reported in source
Transmitochondrial retinal pigment epithelial cybrid cells with AMD or normal mitochondria
Comparator
Untreated cybrids
Outcome group
Neuroprotection · Eye
Source sentences
Summary
HNF₁₄ treatment was associated with improved metabolic activity and reduced cytotoxicity in AMD cybrids
1 context sentence(design, population, supporting numbers)
Summary · context
Transmitochondrial retinal pigment epithelial cybrid cell lines containing mitochondria from AMD patients or age-matched normal donors were treated with HNF₁₄, a 14-amino acid Humanin fragment peptide.
In this study, Humanin 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 Humanin.
Show in the study text Report a problemFND-4182710502
03LabNot a test of Humanin aloneIn vitro (cells)Efficacy outcome
HNF14 had minimal effects in normal cybrids.
In plain wordsIn cells, a short humanin fragment had little effect in cells carrying mitochondria from healthy donors.
Peptide
Humanin
Outcome
No significant changeEffect of HNF14 in normal cybrids
Study
humann: not reported in source
Transmitochondrial retinal pigment epithelial cybrid cells with AMD or normal mitochondria
Comparator
Untreated cybrids
Outcome group
Mitochondrial function · Eye
Source sentences
Summary
with minimal effects in normal cybrids.
2 context sentences(design, population, supporting numbers)
Summary · context
These effects were selective for cybrids containing AMD-derived mitochondria.
Summary · context
Transmitochondrial retinal pigment epithelial cybrid cell lines containing mitochondria from AMD patients or age-matched normal donors were treated with HNF₁₄, a 14-amino acid Humanin fragment peptide.
In this study, Humanin 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 Humanin.
Show in the study text Report a problemFND-4182710503
04LabNot a test of Humanin aloneIn vitro (cells)Efficacy outcome
HNF14 significantly reduced intracellular oxidative stress in AMD cybrids.
In plain wordsIn cells, a short humanin fragment reduced oxidative stress inside cells carrying AMD-type mitochondria.
Peptide
Humanin
Outcome
DecreaseIntracellular oxidative stress in AMD cybrids
Study
humann: not reported in source
Transmitochondrial retinal pigment epithelial cybrid cells with AMD or normal mitochondria
Comparator
Untreated cybrids
Outcome group
Mitochondrial function · Eye
Source sentences
Summary
HNF₁₄ significantly reduced intracellular and mitochondrial oxidative stress
1 context sentence(design, population, supporting numbers)
Summary · context
Transmitochondrial retinal pigment epithelial cybrid cell lines containing mitochondria from AMD patients or age-matched normal donors were treated with HNF₁₄, a 14-amino acid Humanin fragment peptide.
In this study, Humanin 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 Humanin.
Show in the study text Report a problemFND-4182710504
05LabNot a test of Humanin aloneIn vitro (cells)Efficacy outcome
HNF14 significantly reduced mitochondrial oxidative stress in AMD cybrids.
In plain wordsIn cells, a short humanin fragment reduced oxidative stress in the mitochondria of cells carrying AMD-type mitochondria.
Peptide
Humanin
Outcome
DecreaseMitochondrial oxidative stress in AMD cybrids
Study
humann: not reported in source
Transmitochondrial retinal pigment epithelial cybrid cells with AMD or normal mitochondria
Comparator
Untreated cybrids
Outcome group
Mitochondrial function · Eye
Source sentences
Summary
HNF₁₄ significantly reduced intracellular and mitochondrial oxidative stress
1 context sentence(design, population, supporting numbers)
Summary · context
Transmitochondrial retinal pigment epithelial cybrid cell lines containing mitochondria from AMD patients or age-matched normal donors were treated with HNF₁₄, a 14-amino acid Humanin fragment peptide.
In this study, Humanin 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 Humanin.
Show in the study text Report a problemFND-4182710505
06LabNot a test of Humanin aloneIn vitro (cells)Efficacy outcome
HNF14 suppressed apoptotic markers in AMD cybrids.
In plain wordsIn cells, a short humanin fragment lowered markers of cell death in cells carrying AMD-type mitochondria.
Peptide
Humanin
Outcome
DecreaseApoptotic markers in AMD cybrids
Study
humann: not reported in source
Transmitochondrial retinal pigment epithelial cybrid cells with AMD or normal mitochondria
Comparator
Untreated cybrids
Outcome group
Neuroprotection · Eye
Source sentences
Summary
suppressed apoptotic and inflammatory markers, and decreased VEGF-A protein expression in AMD cybrids.
1 context sentence(design, population, supporting numbers)
Summary · context
Transmitochondrial retinal pigment epithelial cybrid cell lines containing mitochondria from AMD patients or age-matched normal donors were treated with HNF₁₄, a 14-amino acid Humanin fragment peptide.
In this study, Humanin 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 Humanin.
Show in the study text Report a problemFND-4182710506
07LabNot a test of Humanin aloneIn vitro (cells)Efficacy outcome
HNF14 suppressed inflammatory markers in AMD cybrids.
In plain wordsIn cells, a short humanin fragment lowered markers of inflammation in cells carrying AMD-type mitochondria.
Peptide
Humanin
Outcome
DecreaseInflammatory markers in AMD cybrids
Study
humann: not reported in source
Transmitochondrial retinal pigment epithelial cybrid cells with AMD or normal mitochondria
Comparator
Untreated cybrids
Outcome group
Inflammation markers · Eye
Source sentences
Summary
suppressed apoptotic and inflammatory markers, and decreased VEGF-A protein expression in AMD cybrids.
1 context sentence(design, population, supporting numbers)
Summary · context
Transmitochondrial retinal pigment epithelial cybrid cell lines containing mitochondria from AMD patients or age-matched normal donors were treated with HNF₁₄, a 14-amino acid Humanin fragment peptide.
In this study, Humanin 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 Humanin.
Show in the study text Report a problemFND-4182710507
08LabNot a test of Humanin aloneIn vitro (cells)Efficacy outcome
HNF14 decreased VEGF-A protein expression in AMD cybrids.
In plain wordsIn cells, a short humanin fragment lowered VEGF-A protein in cells carrying AMD-type mitochondria.
Peptide
Humanin
Outcome
DecreaseVEGF-A protein expression in AMD cybrids
Study
humann: not reported in source
Transmitochondrial retinal pigment epithelial cybrid cells with AMD or normal mitochondria
Comparator
Untreated cybrids
Outcome group
Angiogenesis · Eye
Source sentences
Summary
decreased VEGF-A protein expression in AMD cybrids.
1 context sentence(design, population, supporting numbers)
Summary · context
Transmitochondrial retinal pigment epithelial cybrid cell lines containing mitochondria from AMD patients or age-matched normal donors were treated with HNF₁₄, a 14-amino acid Humanin fragment peptide.
In this study, Humanin 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 Humanin.
Show in the study text Report a problemFND-4182710508
09LabNot a test of Humanin aloneIn vitro (cells)Efficacy outcome
HNF14 attenuated amyloid-β 1-42 induced apoptotic signaling in AMD cybrids.
In plain wordsIn cells, a short humanin fragment reduced cell death signals caused by amyloid-β in cells carrying AMD-type mitochondria.
Peptide
Humanin
Outcome
DecreaseAmyloid-beta 1-42 induced apoptotic signaling in AMD cybrids
Study
humann: not reported in source
Transmitochondrial retinal pigment epithelial cybrid cells with AMD or normal mitochondria
Comparator
Untreated cybrids
Outcome group
Neuroprotection · Eye
Source sentences
Summary
In addition, HNF₁₄ attenuated amyloid-β_1-42-induced apoptotic signaling in AMD cybrids.
1 context sentence(design, population, supporting numbers)
Summary · context
Transmitochondrial retinal pigment epithelial cybrid cell lines containing mitochondria from AMD patients or age-matched normal donors were treated with HNF₁₄, a 14-amino acid Humanin fragment peptide.
In this study, Humanin 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 Humanin.
Show in the study text Report a problemFND-4182710509

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
13 Oct 2026, 21:44 UTC
Study results updated
Version 1
13 Oct 2026, 16:31 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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Keywords

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