IGF-I regulates the age-dependent signaling peptide humanin.

Lee C, Wan J, Miyazaki B, Fang Y, Guevara-Aguirre J, Yen K, Longo V, Bartke A, Cohen P

Aging cell18 Jul 2014Cited by 71 (Europe PMC)

PMID25040290PMCIDPMC4172517DOI10.1111/acel.12243PepBankPUB-25040290

Summary

Aging is influenced by endocrine pathways including the growth hormone/insulin-like growth factor-1 (GH/IGF) axis. Mitochondrial function has also been linked to the aging process, but the relevant mitochondrial signals mediating the effects of mitochondria are poorly understood. Humanin is a novel signaling peptide that acts as a potent regulator of cellular stress responses and protects from a variety of in vitro and in vivo toxic and metabolic insults. The circulating levels of humanin decline with age in mice and humans. Here, we demonstrate a negative correlation between the activity of the GH-IGF axis and the levels of humanin, as well as a positive correlation between humanin and lifespan in mouse models with altered GH/IGF-I axis. Long-lived, GH-deficient Ames mice displayed elevated humanin levels, while short-lived GH-transgenic mice have reduced humanin levels. Furthermore, treatment with GH or IGF-I reduced circulating humanin levels in both mice and human subjects. Our results indicate that GH and IGF are potent regulators of humanin levels and that humanin levels correlate with lifespan in mice. This suggests that humanin represents a circulating mitochondrial signal that participates in modulating the aging process, adding a coordinated mitochondrial element to the endocrine regulation of aging.

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 levelOther designMechanism
Treatment with GH or IGF-I reduced circulating humanin levels in human subjects.
In plain wordsIn people, growth hormone or IGF-I treatment lowered the body's own humanin levels in the blood.
Peptide
Humanin
Outcome
DecreaseCirculating humanin after GH or IGF-I treatment in humans
Study
n: not reported in source
Outcome group
Aging markers · Aging and longevity
Source sentences
Summary
Furthermore, treatment with GH or IGF-I reduced circulating humanin levels in both mice and human subjects.
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-2504029004
02AnimalEndogenous levelAnimal study (in vivo)Other
Long-lived, GH-deficient Ames mice had elevated humanin levels.
In plain wordsIn mice, long-lived Ames mice that lack growth hormone had higher levels of the body's own humanin.
Peptide
Humanin
Outcome
IncreaseHumanin level in GH-deficient Ames mice
Study
mousen: not reported in source
Ames mice (GH-deficient, long-lived)
Outcome group
Aging markers · Aging and longevity
Source sentences
Summary
Long-lived, GH-deficient Ames mice displayed elevated humanin levels, while short-lived GH-transgenic mice have reduced humanin levels.
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-2504029001
03AnimalEndogenous levelAnimal study (in vivo)Other
Short-lived GH-transgenic mice had reduced humanin levels.
In plain wordsIn mice, short-lived mice with extra growth hormone had lower levels of the body's own humanin.
Peptide
Humanin
Outcome
DecreaseHumanin level in GH-transgenic mice
Study
mousen: not reported in source
GH-transgenic mice (short-lived)
Outcome group
Aging markers · Aging and longevity
Source sentences
Summary
Long-lived, GH-deficient Ames mice displayed elevated humanin levels, while short-lived GH-transgenic mice have reduced humanin levels.
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-2504029002
04AnimalEndogenous levelAnimal study (in vivo)Mechanism
Treatment with GH or IGF-I reduced circulating humanin levels in mice.
In plain wordsIn mice, growth hormone or IGF-I treatment lowered the body's own humanin levels in the blood.
Peptide
Humanin
Outcome
DecreaseCirculating humanin after GH or IGF-I treatment in mice
Study
mousen: not reported in source
mice treated with GH or IGF-I
Outcome group
Aging markers · Aging and longevity
Source sentences
Summary
Furthermore, treatment with GH or IGF-I reduced circulating humanin levels in both mice and human subjects.
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-2504029003
05AnimalEndogenous levelAnimal study (in vivo)Mechanism
In mouse models with an altered GH/IGF-I axis, GH-IGF axis activity correlated negatively with humanin levels.
In plain wordsIn mice, higher growth hormone and IGF activity went with lower levels of the body's own humanin.
Peptide
Humanin
Outcome
Not applicableCorrelation between GH-IGF axis activity and humanin level
Study
mousen: not reported in source
mouse models with altered GH/IGF-I axis
Outcome group
Aging markers · Aging and longevity
Source sentences
Summary
Here, we demonstrate a negative correlation between the activity of the GH-IGF axis and the levels of humanin, as well as a positive correlation between humanin and lifespan in mouse models with altered GH/IGF-I axis.
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-2504029005
06AnimalEndogenous levelAnimal study (in vivo)Mechanism
In mouse models with an altered GH/IGF-I axis, humanin levels correlated positively with lifespan.
In plain wordsIn mice, higher levels of the body's own humanin were linked to longer lifespan.
Peptide
Humanin
Outcome
Not applicableCorrelation between humanin level and lifespan
Study
mousen: not reported in source
mouse models with altered GH/IGF-I axis
Outcome group
Aging markers · Aging and longevity
Source sentences
Summary
Here, we demonstrate a negative correlation between the activity of the GH-IGF axis and the levels of humanin, as well as a positive correlation between humanin and lifespan in mouse models with altered GH/IGF-I axis.
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-2504029006

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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