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Cited by 286

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 access
Cobb, Laura J., Lee, Changhan, Xiao, Jialin, Yen, Kelvin, Wong, Richard G., Nakamura, Hiromi K., Mehta, Hemal H., Gao, Qinglei, Ashur, Carmel, Huffman, Derek M., Wan, Junxiang, Muzumdar, Radhika, Barzilai, Nir, Cohen, Pinchas·2016·Aging

Abstract

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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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
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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CoChat. (2026). Citation check: Naturally occurring mitochondrial-derived peptides are age-dependent regulators of apoptosis, insulin sensitivity, and inflammatory markers. https://app.cochat.ai/papers/10.18632/aging.100943
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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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