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

Jun 25, 2020

Contributor: 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

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

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 the overexpression of humanin is sufficient to increase lifespan, dependent on . 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.

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About The Expert

Kelvin Yen

Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA.

Hemal H Mehta

Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA.

Su-Jeong Kim

Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA.

YanHe Lue

Department of Medicine, The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.

James Hoang

Department of Medicine, The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.

Noel Guerrero

Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA.

Jenna Port

Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA.

Qiuli Bi

Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA.

Gerardo Navarrete

Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA.

Sebastian Brandhorst

Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA.

Kaitlyn Noel Lewis

Department of Physiology, The Barshop Institute, University of Texas Health at San Antonio, TX 78229, USA.

Junxiang Wan

Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA.

Ronald Swerdloff

Department of Medicine, The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.

Julie A Mattison

Translational Gerontology Branch, National Institute on Aging, Dickerson, MD 20892, USA.

Rochelle Buffenstein

Department of Physiology, The Barshop Institute, University of Texas Health at San Antonio, TX 78229, USA.

Calico Life Sciences, South San Francisco, CA 94080, USA.

Carrie V Breton

Department of Preventive Medicine, Keck School of Medicine, USC, Los Angeles, CA 90089, USA.

Christina Wang

Department of Medicine, The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.

Valter Longo

Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA.

Gil Atzmon

Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

Department of Human Biology, Faculty of Natural Science, University of Haifa, Haifa, Israel.

Douglas Wallace

Center for Mitochondrial and Epigenomic Medicine, Children’s Hospital of Philadelphia, Department of Pediatrics, Division of Human Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Nir Barzilai

Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

Pinchas Cohen

Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA.

References

PubMed