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Study · Not a test of the peptide alone · 2026

3 results

Humanin as an evolutionarily tuned mitochondrial peptide: Insights from mammalian oxidative stress diversity.

Shahzaib M, Aprile D, Alessio N, Laporta G, Peluso G, Di Bernardo G, Galderisi U

Free radical biology & medicine20 Mar 2026

PMID41864362 (opens in a new tab)DOI10.1016/j.freeradbiomed.2026.03.033 (opens in a new tab)PepBankPUB-41864362
Publisher pagePubMedAsk about this study
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Summary

Humanin is a mitochondrial-derived peptide with cytoprotective properties, but how it has evolved in response to different oxidative stress levels in mammals is not fully understood. This study examines how Humanin sequences have adapted to species-specific metabolic and environmental pressures. We compared the peptide in several mammalian species categorized by their distinct oxidative stress profiles: small mammals such as shrews with high metabolic rates and elevated endogenous ROS production, cetaceans exposed to hypoxia-reoxygenation cycles during deep diving, and long-lived primates facing cumulative oxidative stress over extended lifespans. Using bioinformatic tools, we analyzed physicochemical traits such as structural stability, the aliphatic index, and oxidation susceptibility. We also used protein-protein docking to estimate binding affinities between Humanin variants and key ligands like BAX and FPRL1. Our results show that Humanin is not a static molecule. Species facing high oxidative stress, such as cetaceans and bats, possess variants that are more stable and chemically robust. In contrast, species with high ROS production but lower antioxidant capacity, like the shrew, have less robust versions of the peptide. Simulation data indicate that variants from mammals living in extreme conditions maintain or improve interactions with proteins involved in cell survival. These findings suggest that evolution has tuned Humanin to optimize mitochondrial protection across different physiological contexts. These natural isoforms provide a structural basis for designing new therapeutic analogs to treat oxidative stress-related diseases in humans.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study3

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

Studies that did not test the peptide alone3

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.

  1. 01Computer modelNot a test of Humanin aloneIn silicoMechanism

    In a computational comparison, humanin variants from species facing high oxidative stress, such as cetaceans and bats, were more stable and chemically robust.

    In plain wordsIn computer analysis, humanin variants from whales, dolphins and bats were predicted to be more stable and chemically robust.

    Peptide
    Humanin
    Outcome
    Not applicableStability and chemical robustness of humanin variants in species under high oxidative stress
    Study

    mammals (shrews, cetaceans, bats, primates)n: not reported in source

    Humanin sequence variants analysed with bioinformatic tools and protein-protein docking
    Outcome group
    Receptor activity and mechanism · Pharmacology

    Source sentences

    Summary
    Species facing high oxidative stress, such as cetaceans and bats, possess variants that are more stable and chemically robust.
    2 context sentences
    Summary · context
    We compared the peptide in several mammalian species categorized by their distinct oxidative stress profiles: small mammals such as shrews with high metabolic rates and elevated endogenous ROS production, cetaceans exposed to hypoxia-reoxygenation cycles during deep diving, and long-lived primates facing cumulative oxidative stress over extended lifespans.
    Summary · context
    Using bioinformatic tools, we analyzed physicochemical traits such as structural stability, the aliphatic index, and oxidation susceptibility.

    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.

  2. 02Computer modelNot a test of Humanin aloneIn silicoMechanism

    In a computational comparison, the shrew humanin variant was less robust than variants from other species.

    In plain wordsIn computer analysis, the shrew humanin variant was predicted to be less robust.

    Peptide
    Humanin
    Outcome
    Not applicableRobustness of humanin variants in the shrew
    Study

    mammals (shrews, cetaceans, bats, primates)n: not reported in source

    Humanin sequence variants analysed with bioinformatic tools and protein-protein docking
    Outcome group
    Receptor activity and mechanism · Pharmacology

    Source sentences

    Summary
    In contrast, species with high ROS production but lower antioxidant capacity, like the shrew, have less robust versions of the peptide.
    2 context sentences
    Summary · context
    We compared the peptide in several mammalian species categorized by their distinct oxidative stress profiles: small mammals such as shrews with high metabolic rates and elevated endogenous ROS production, cetaceans exposed to hypoxia-reoxygenation cycles during deep diving, and long-lived primates facing cumulative oxidative stress over extended lifespans.
    Summary · context
    Using bioinformatic tools, we analyzed physicochemical traits such as structural stability, the aliphatic index, and oxidation susceptibility.

    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.

  3. 03Computer modelNot a test of Humanin aloneIn silicoMechanism

    In docking simulations, humanin variants from mammals living in extreme conditions maintained or improved interactions with proteins involved in cell survival.

    In plain wordsIn computer simulations, humanin variants from animals in extreme conditions were predicted to keep or improve binding to cell-survival proteins.

    Peptide
    Humanin
    Outcome
    Not applicablePredicted interactions of humanin variants with cell-survival proteins
    Study

    mammals (shrews, cetaceans, bats, primates)n: not reported in source

    Humanin sequence variants analysed with bioinformatic tools and protein-protein docking
    Outcome group
    Receptor activity and mechanism · Pharmacology

    Source sentences

    Summary
    Simulation data indicate that variants from mammals living in extreme conditions maintain or improve interactions with proteins involved in cell survival.
    3 context sentences
    Summary · context
    We also used protein-protein docking to estimate binding affinities between Humanin variants and key ligands like BAX and FPRL1.
    Summary · context
    We compared the peptide in several mammalian species categorized by their distinct oxidative stress profiles: small mammals such as shrews with high metabolic rates and elevated endogenous ROS production, cetaceans exposed to hypoxia-reoxygenation cycles during deep diving, and long-lived primates facing cumulative oxidative stress over extended lifespans.
    Summary · context
    Using bioinformatic tools, we analyzed physicochemical traits such as structural stability, the aliphatic index, and oxidation susceptibility.

    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.

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

    13 Oct 2026, 21:44 UTC

    Study results updated

  2. Version 1

    13 Oct 2026, 16:31 UTC

    First added · source update from Europe PMC

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