Tested in both mice and human cells, the proteins may lead to greater understanding of aging-related diseases, from diabetes to Alzheimer’s to cancer, according to researchers at USC Davis School of Gerontology who led the study.
Researchers have identified a group of six proteins that they believe may divulge secrets of how we age and unlock new insights into diabetes, Alzheimer’s, cancer, and other aging-related diseases.
Nicknamed “Schlep” or “SHLP” for “small humanin-like peptides,” these proteins appear to play several big roles in our bodies’ cells, from decreasing the amount of damaging free radicals and controlling the rate at which cells die, to boosting metabolism and helping tissues throughout the body respond better to insulin. The naturally occurring amounts of each protein decrease with age, leading researchers to believe that they play an important role in the aging process and the onset of age-related diseases.
The research team led by Pinchas Cohen, dean and professor of the USC Leonard Davis School of Gerontology, identified the tiny proteins for the first time and observed their surprising origin: organelles in the cell called mitochondria and their game-changing roles in metabolism and cell survival.
This latest finding builds upon prior research by Cohen and his team that uncovered two significant proteins, humanin and MOTS-c, hormones that appear to have significant roles in metabolism and diseases of aging.
Unlike most other proteins, humanin and MOTS-c are encoded in mitochondria, the structure within cells that produces energy from food, instead of in the cell’s nucleus where most genes are contained.
Mitochondria have their own small collection of genes, which were once thought to play only minor roles within cells, but recent research indicates that they have important functions throughout the body.
Cohen’s team used computer analysis to see if the part of the mitochondrial genome that provides the code for humanin was coding for other proteins as well, and uncovered the six new proteins.
The team examined both mouse tissues and human cells to determine their abundance in different organs, as well as their functions. The proteins were distributed quite differently among organs, which suggests that the proteins have varying functions based on where they are in the body.
Of particular interest is SHLP 2, Cohen said. The protein appears to have profound insulin-sensitizing, anti-diabetic effects as well as potent neuro-protective activity that may emerge as a strategy to combat Alzheimer’s disease. He added that SHLP 6 is also intriguing, with a unique ability to promote cancer cell death and thus potentially target malignant diseases.
“Together, with the previously identified mitochondrial peptides, the newly recognized SHLP family expands the understanding of the mitochondria as an intracellular signaling organelle that communicates with the rest of the body to regulate metabolism and cell fate,” Cohen said. “The findings are an important advance that will be ripe for rapid translation into drug development for diseases of aging.”
The study, “Naturally Occurring Mitochondrial-Derived Peptides are Age-Dependent Regulators of Apoptosis, Insulin Sensitivity, and Inflammatory Markers” first appeared online in the journal Aging on April 10. Cohen’s research team included collaborators from the Albert Einstein College of Medicine, and the findings have been licensed to the biotechnology company CohBar for possible drug development.
Funding: The research was supported by a Glenn Foundation Award and National Institutes of Health grants to Cohen, and an Ellison/AFAR post-doctoral fellowship to Kelvin Yen. Study co-authors Laura Cobb, Changhan Lee, Nir Barzilai, and Pinchas Cohen are consultants and stockholders of CohBar Inc.
NeuroscienceNews.com would like to thank Beth Newcomb for submitting this news release directly to us for inclusion on the website.
Source: Beth Newcomb – USC
Image Credit: The image is adapted from the USC press release.
Original Research: Full open access research for “Naturally occurring mitochondrial-derived peptides are age-dependent regulators of apoptosis, insulin sensitivity, and inflammatory markers” by Laura J Cobb, Changhan Lee, Jialin Xiao, Kelvin Yen, Richard G Wong, Hiromi K. Nakamura, Hemal H. Mehta, Qinglei Gao, Carmel Ashur, Derek M. Huffman, Junxiang Wan, Radhika Muzumdar, Nir Barzilai, and Pinchas Cohen in Aging. Published online April 10 2016 doi:Not Available
Naturally occurring mitochondrial-derived peptides are age-dependent regulators of apoptosis, insulin sensitivity, and inflammatory markers
Mitochondria are key players in aging and in the pathogenesis of age-related diseases. Recent mitochondrial transcriptome analyses revealed the existence of multiple small mRNAs transcribed from mitochondrial DNA (mtDNA). Humanin (HN), a peptide encoded in the mtDNA 16S ribosomal RNA region, is a neuroprotective factor. An in silico search revealed six additional peptides in the same region of mtDNA as humanin; we named these peptides small humanin-like peptides (SHLPs). We identified the functional roles for these peptides and the potential mechanisms of action. The SHLPs differed in their ability to regulate cell viability in vitro. We focused on SHLP2 and SHLP3 because they shared similar protective effects with HN. Specifically, they significantly reduced apoptosis and the generation of reactive oxygen species, and improved mitochondrial metabolism in vitro. SHLP2 and SHLP3 also enhanced 3T3-L1 pre-adipocyte differentiation. Systemic hyperinsulinemic-euglycemic clamp studies showed that intracerebrally infused SHLP2 increased glucose uptake and suppressed hepatic glucose production, suggesting that it functions as an insulin sensitizer both peripherally and centrally. Similar to HN, the levels of circulating SHLP2 were found to decrease with age. These results suggest that mitochondria play critical roles in metabolism and survival through the synthesis of mitochondrial peptides, and provide new insights into mitochondrial biology with relevance to aging and human biology.
“Naturally occurring mitochondrial-derived peptides are age-dependent regulators of apoptosis, insulin sensitivity, and inflammatory markers” by Laura J Cobb, Changhan Lee, Jialin Xiao, Kelvin Yen, Richard G Wong, Hiromi K. Nakamura, Hemal H. Mehta, Qinglei Gao, Carmel Ashur, Derek M. Huffman, Junxiang Wan, Radhika Muzumdar, Nir Barzilai, and Pinchas Cohen in Aging. Published online April 10 2016 doi:Not Available