Humanin Prevents Age-Related Cognitive Decline in Mice and is Associated with Improved Cognitive Age in Humans

Yen, Kelvin; Wan, Junxiang; Mehta, Hemal H.; Miller, Brendan; Christensen, A. Kent; Levine, Morgan E.; Salomon, Matthew P.; Brandhorst, Sebastian; Xiao, Jialin; Kim, Su-Jeong; Navarrete, Gerardo; Campo, Daniel; Harry, G. Jean; Longo, Valter D.; Pike, Christian J.; Mack, Wendy J.; Hodis, Howard N.; Crimmins, Eileen M.; Cohen, Pinchas

doi:10.1038/s41598-018-32616-7

Cited by 77 publications

(64 citation statements)

References 57 publications

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“…Qin et al (2018) [9] have highlighted that exogenous HN treatment attenuated myocardial fibrosis and apoptosis in aged mice, suggesting a role for the mitochondria-derived peptide HN in cardioprotection. The study by Yen et al (2018) [10] addressed to HN a role in neuroprotection against cognitive aging in humans. In addition, Solanki et al (2018) [11] proposed a potential application of a HN derivative for treating age-related macular degeneration (AMD) since AGA-HNG may represent a promising therapeutic option for AMD.…”

Section: Discussionmentioning

confidence: 99%

Humanin gene expression in fibroblast of Down syndrome subjects

Salemi¹,

Ridolfo²,

Salluzzo³

et al. 2020

Int. J. Med. Sci.

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Down syndrome (DS) is characterized by trisomy of chromosome 21 and peculiar phenotype. Humanin (HN) is a mitochondrial short 24-residue polypeptide whit anti-apoptotic and neuroprotective effects. In this study we evaluated HN protein expression and HN mRNA levels in cultured fibroblasts from DS patients and normal controls. Our results obtained by immunocytochemistry, western-blot and qRT-PCR analysis show a significant HN up-regulation in DS patients. These results confirm previous studies and suggest a role for HN may in the DS phenotype.

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Section: Discussionmentioning

confidence: 99%

Humanin gene expression in fibroblast of Down syndrome subjects

Salemi¹,

Ridolfo²,

Salluzzo³

et al. 2020

Int. J. Med. Sci.

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“…Humanin, which was the first MDP discovered, was identified as a neuroprotective peptide using a screen searching for genes that could protect neuronal cells from amyloid-β toxicity (Hashimoto et al 2001 ; Hashimoto et al 2001a ; Hashimoto et al 2001b ; Yen et al 2018 ). It was later found to be an IGFBP-3 interacting protein and exerts its anti-apoptotic functions through direct binding to IGFBP-3 (Ikonen et al 2003 ).…”

Section: Introductionmentioning

confidence: 99%

“…It was later found to be an IGFBP-3 interacting protein and exerts its anti-apoptotic functions through direct binding to IGFBP-3 (Ikonen et al 2003 ). Over the past decade, the effects and mechanism of humanin action have been carefully characterized (Harada et al 2004 ; Kim et al 2016 ; Muzumdar et al 2009 ; Nashine et al 2017 ; Qin et al 2018 ; Yen et al 2018 ; Ying et al 2004 ). Humanin protects cells against various insults, such as oxidative damage and amyloid toxicity (Chai et al 2014 ; Klein et al 2013 ; Okada et al 2017 ; Paharkova et al 2015 ; Romeo et al 2017 ; Thummasorn et al 2016 ; Thummasorn et al 2017 ; Thummasorn et al 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Metabolomic profile of diet-induced obesity mice in response to humanin and small humanin-like peptide 2 treatment

et al. 2019

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Introduction The mitochondrial-derived peptides (MDPs) are a novel group of natural occurring peptides that have important signaling functions and biological activity. Both humanin and small-humanin-like peptide 2 (SHLP2) have been reported to act as insulin sensitizers and modulate metabolism. Objectives By using a metabolomic approach, this study explores how the plasma metabolite profile is regulated in response to humanin and SHLP2 treatment in a diet-induced obesity (DIO) mouse model. The results also shed light on the potential mechanism underlying MDPs’ insulin sensitization effects. Methods Plasma samples were obtained from DIO mice subjected to vehicle (water) treatment, or peptide treatment with either humanin analog S14G (HNG) or SHLP2 (n = 6 per group). Vehicle or peptides were given as intraperitoneal (IP) injections twice a day at dose of 2.5 mg/kg/injection for 3 days. Metabolites in plasma samples were comprehensively identified and quantified using UPLC-MS/MS. Results HNG and SHLP2 administration significantly altered the concentrations of amino acid and lipid metabolites in plasma. Among all the metabolic pathways, the glutathione and sphingolipid metabolism responded most strongly to the peptide treatment. Conclusions The present study indicates that humanin and SHLP2 can lower several markers associated with age-related metabolic disorders. With the previous understanding of the effects of humanin and SHLP2 on cardiovascular function, insulin sensitization, and anti-inflammation, this metabolomic discovery provides a more comprehensive molecular explanation of the mechanism of action for humanin and SHLP2 treatment. Electronic supplementary material The online version of this article (10.1007/s11306-019-1549-7) contains supplementary material, which is available to authorized users.

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“…Humanin, small humanin-like peptides (SHLPs), MOTS-c, and emerging new mitochondrial-derived peptides have highly specific and profound effects on various systems and organs. [28][29][30][31][32][33][34] Yen et al 27 reported that an mtSNP in the humanin smORF was associated with lower circulating levels of humanin and worse cognitive function. Moreover, the mitochondrialderived peptides SHLP2 and humanin protected against a model of macular degeneration in vitro.…”

Section: Discussionmentioning

confidence: 99%

A Mitochondrial Genome-Wide Association Study of Cataract in a Latino Population

Miller

Torres

Jiang

et al. 2020

Trans. Vis. Sci. Tech.

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Over 9.5 million Latinos could be affected by cataracts by 2050. However, no known cataract genetic risk alleles have been identified in Latinos. Moreover, no mitochondrial genome-wide association studies (MiWAS) have been conducted on cataracts in a Latino cohort despite the association between mitochondrial dysfunction and cataracts. Our purpose was to identify a mitochondrial DNA variant that associated with cataracts in a large-scale Latino population. Methods: We conducted an MiWAS to identify mitochondrial single-nucleotide polymorphisms that modify cataract risk in nearly 3500 individuals enrolled in the Los Angles Latino Eye Study cohort, the largest Latino-specific cohort with comprehensive cataract data. Our analytic strategy for MiWAS included logistic regression on cataract occurrence while controlling for mitochondrial genetic ancestry, age, and biological sex. Results: We found that MitoG228A (rs41323649) alternative allele carriers experienced a five times greater risk for cataracts compared with reference allele carriers. Alternative allele carriers also developed cataracts earlier in life compared with reference allele carriers. Intracohort cross-validation with 10-fold resampling and five repeats showed that the effect of MitoG228A remained significant. Conclusions: MitoG228A increased risk for cataracts five-fold in approximately 3500 Latinos. To the best of our knowledge, this is the first cataract MiWAS on a largescale Latino population. This association needs to be validated in an independent cohort. Translational Relevance: Our discovery hypothesis-generating study suggest MitoG228A has potential to be used as a risk factor in the clinic and as a target for therapeutics. With validation via an independent cohort, MitoG228A could be used to estimate cataract risk for a Latino to reduce complications later in life.

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Humanin Prevents Age-Related Cognitive Decline in Mice and is Associated with Improved Cognitive Age in Humans

Cited by 77 publications

References 57 publications

Humanin gene expression in fibroblast of Down syndrome subjects

Humanin gene expression in fibroblast of Down syndrome subjects

Metabolomic profile of diet-induced obesity mice in response to humanin and small humanin-like peptide 2 treatment

A Mitochondrial Genome-Wide Association Study of Cataract in a Latino Population

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