The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
Naturally occurring mitochondrial-derived peptides are age-dependent regulators of apoptosis, insulin sensitivity, and inflammatory markers
Open accessAbstract
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.
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Cites
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ResultLow-Grade Systemic Inflammation and the Development of Type 2 Diabetes
Duncan, B. B., Schmidt, M. I., Pankow, J. S., Ballantyne, C. M., Couper, D., Vigo, A., Hoogeveen, R., Folsom, A. R., & Heiss, G. (2003) · Diabetes · doi:10.2337/diabetes.52.7.1799 · Cited by 1,036
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Cited by
Mitochondria-associated programmed cell death as a therapeutic target for age-related disease
Nguyen, T. T., Wei, S., Nguyen, T. H., Jo, Y., Zhang, Y., Park, W., Gariani, K., Oh, C.-M., Kim, H. H., Ha, K.-T., et al. (2023) · Experimental & Molecular Medicine · doi:10.1038/s12276-023-01046-5 · Cited by 325
Functional Mitochondria in Health and Disease
Herst, P. M., Rowe, M. R., Carson, G. M., & Berridge, M. V. (2017) · Frontiers in Endocrinology · doi:10.3389/fendo.2017.00296 · Cited by 323
Human Aging and Longevity Are Characterized by High Levels of Mitokines
Conte, M., Ostan, R., Fabbri, C., Santoro, A., Guidarelli, G., Vitale, G., Mari, D., Sevini, F., Capri, M., Sandri, M., et al. (2019) · The Journals of Gerontology: Series A · doi:10.1093/gerona/gly153 · Cited by 219
Senescence in the pathogenesis of age-related macular degeneration
Blasiak, J. (2020) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03420-x · Cited by 183
MOTS-c: a novel mitochondrial-derived peptide regulating muscle and fat metabolism
Lee, C., Kim, K. H., & Cohen, P. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.05.015 · Cited by 178
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Metadata
- Authors
- Cobb, L. J., Lee, C., Xiao, J., Yen, K., Wong, R. G., Nakamura, H. K., Mehta, H. H., Gao, Q., Ashur, C., Huffman, D. M., Wan, J., Muzumdar, R., Barzilai, N., & Cohen, P.
- Venue
- Aging
- Publisher
- Impact Journals, LLC
- Published
- 2016-04-10
- Volume
- 8
- Issue
- 4
- Pages
- 796-809
- ISSN
- 1945-4589 (ISSN-L)
- OpenAlex
- W2396191679
- Cited by
- 286
- References
- 48
- FWCI
- 11.44
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Cobb, L. J., Lee, C., Xiao, J., Yen, K., Wong, R. G., Nakamura, H. K., Mehta, H. H., Gao, Q., Ashur, C., Huffman, D. M., Wan, J., Muzumdar, R., Barzilai, N., & Cohen, P. (2016). Naturally occurring mitochondrial-derived peptides are age-dependent regulators of apoptosis, insulin sensitivity, and inflammatory markers. Aging. https://doi.org/10.18632/aging.100943
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