Mitochondrial Peptide Protects Brain from Age-Related Dementias

Humanin (HN) is a 24-amino acid mitochondria-associated peptide. Since its initial discovery more than 10 years ago, a role for HN has been reported in many biological processes such as apoptosis, cell survival, substrate metabolism, inflammatory response, and response to stressors such as oxidative stress, ischemia, and starvation. Mounting evidence has suggested that HN and other mitochondrial derived peptides play a role in several age-related conditions including neurodegenerative disease.

In light of findings that HN levels decrease with age, investigators at the University of Southern California (Los Angeles, USA) sought to confirm that humanin played an important function in the aging process and the onset of age-related diseases.

To this end, they used a mitochondrial GWAS (genome-wide association study) to identify a specific single-nucleotide polymorphism (SNP) in the humanin-coding region of the mitochondrial genome that was associated with a 14% decrease in circulating humanin levels. In a large, independent cohort, consisting of a nationally representative sample of older adults, the investigators found that this SNP was associated with accelerated cognitive aging; supporting the concept that humanin is an important factor in cognitive aging.

The investigators further reported in the September 21, 2018, online edition of the journal Scientific Reports that mice injected with humanin experienced a delay in cognitive decline associated with aging.

"Because of the beneficial effects of humanin, a decrease in circulating levels could lead to an increase in several different diseases of aging, particularly in dementia," said senior author Dr. Pinchas Cohen, professor of gerontology, medicine, and biological sciences at the University of Southern California. "This provides the first evidence that a variation in the sequence of a mitochondrial peptide is associated with a change in the level of peptides and the first conclusive demonstration that mitochondrial peptides are encoded in and regulated through mitochondrial DNA."

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