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 PMID:32575074  

The mitochondrial derived peptide humanin is a regulator of lifespan and healthspan.

Kelvin Yen | Hemal H Mehta | Su-Jeong Kim | YanHe Lue | James Hoang | Noel Guerrero | Jenna Port | Qiuli Bi | Gerardo Navarrete | Sebastian Brandhorst | Kaitlyn Noel Lewis | Junxiang Wan | Ronald Swerdloff | Julie A Mattison | Rochelle Buffenstein | Carrie V Breton | Christina Wang | Valter Longo | Gil Atzmon | Douglas Wallace | Nir Barzilai | Pinchas Cohen
Aging | 2020

Humanin is a member of a new family of peptides that are encoded by short open reading frames within the mitochondrial genome. It is conserved in animals and is both neuroprotective and cytoprotective. Here we report that in C. elegans the overexpression of humanin is sufficient to increase lifespan, dependent on daf-16/Foxo. Humanin transgenic mice have many phenotypes that overlap with the worm phenotypes and, similar to exogenous humanin treatment, have increased protection against toxic insults. Treating middle-aged mice twice weekly with the potent humanin analogue HNG, humanin improves metabolic healthspan parameters and reduces inflammatory markers. In multiple species, humanin levels generally decline with age, but here we show that levels are surprisingly stable in the naked mole-rat, a model of negligible senescence. Furthermore, in children of centenarians, who are more likely to become centenarians themselves, circulating humanin levels are much greater than age-matched control subjects. Further linking humanin to healthspan, we observe that humanin levels are decreased in human diseases such as Alzheimer's disease and MELAS (Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like episodes). Together, these studies are the first to demonstrate that humanin is linked to improved healthspan and increased lifespan.

Pubmed ID: 32575074

Research resources used in this publication

None found

Antibodies used in this publication

None found

Associated grants

  • Agency: NIA NIH HHS, United States
    Id: R01 AG042188
  • Agency: NIH HHS, United States
    Id: P40 OD010440
  • Agency: NIA NIH HHS, United States
    Id: P01 AG021654
  • Agency: NIA NIH HHS, United States
    Id: P30 AG038072
  • Agency: NIA NIH HHS, United States
    Id: R01 AG034430
  • Agency: NIEHS NIH HHS, United States
    Id: R21 ES025870
  • Agency: NIA NIH HHS, United States
    Id: R01 AG068405
  • Agency: NIA NIH HHS, United States
    Id: P01 AG034906
  • Agency: NIA NIH HHS, United States
    Id: P01 AG055369
  • Agency: NIDDK NIH HHS, United States
    Id: P30 DK020541

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COBrA (tool)

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