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Sci Rep. 2018 Sep 21;8(1):14212. doi: 10.1038/s41598-018-32616-7.

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

Author information

1
Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.
2
Department of Pathology, Yale School of Medicine, New Haven, CT, USA.
3
Department of Translational Molecular Medicine, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA, USA.
4
Department of Molecular and Computational Biology, University of Southern California, Los Angeles, CA, USA.
5
Neurotoxicology Group, National Toxicology Program Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, Triangle Park, NC, USA.
6
Departments of Medicine and Preventive Medicine, University of Southern California Atherosclerosis Research Unit, University of Southern California, Los Angeles, CA, USA.
7
Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA. hassy@usc.edu.

Abstract

Advanced age is associated with a decline in cognitive function, likely caused by a combination of modifiable and non-modifiable factors such as genetics and lifestyle choices. Mounting evidence suggests that humanin and other mitochondrial derived peptides play a role in several age-related conditions including neurodegenerative disease. Here we demonstrate that humanin administration has neuroprotective effects in vitro in human cell culture models and is sufficient to improve cognition in vivo in aged mice. Furthermore, in a human cohort, using mitochondrial GWAS, we identified a specific SNP (rs2854128) in the humanin-coding region of the mitochondrial genome that is associated with a decrease in circulating humanin levels. In a large, independent cohort, consisting of a nationally-representative sample of older adults, we find that this SNP is associated with accelerated cognitive aging, supporting the concept that humanin is an important factor in cognitive aging.

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