Evidence map›Paper›PMID 27070352›Full record

ArticleAging2016

Naturally occurring mitochondrial-derived peptides are age-dependent regulators of apoptosis, insulin sensitivity, and inflammatory markers.

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 and 4 more

Open access · hybridAbstract read
In one paragraph

Article in Aging, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 172 papers.

0numbers the graph read from it
0cells of the map it votes in
172citing papers in PubMed
22.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

172 citing papers in PubMed, 277 citations in OpenAlex.

  1. Trial
  2. Trial
  3. A peripheral perspective on brain health: vascular and skeletal muscle contributions.American journal of physiology. Heart and circulatory physiology · 2026
    Review
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  5. Article
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  11. Mitochondrial-derived microproteins in lung disease: insights and implications.American journal of physiology. Lung cellular and molecular physiology · 2026
    Review
  12. Article
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  15. Article
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112 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 5 institutions in 1 country.

Laura J CobbDepartment of Pediatrics, Mattel Children's Hospital, and Division of Endocrinology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Changhan LeeLeonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA.
Jialin XiaoLeonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA.
Kelvin YenLeonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA.
Richard G WongLeonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA.
Hiromi K NakamuraDepartment of Pediatrics, Mattel Children's Hospital, and Division of Endocrinology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Hemal H MehtaLeonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA.
Qinglei GaoDepartment of Pediatrics, Mattel Children's Hospital, and Division of Endocrinology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Carmel AshurDepartment of Pediatrics, Mattel Children's Hospital, and Division of Endocrinology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Derek M HuffmanDepartment of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Junxiang WanLeonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA.
Radhika MuzumdarDepartment of Pediatrics, Children's Hospital of Pittsburgh, Pittsburgh, PA 15224, USA.
Nir BarzilaiDepartment of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Pinchas CohenLeonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA.
University of Southern California · USUniversity of California, Los Angeles · USAlbert Einstein College of Medicine · USChildren's Hospital of Pittsburgh · USMattel Children's Hospital · US

Funding

RESEARCH TRAININGP30DK026687 · NIDDK · ST. LUKE'S-ROOSEVELT INST FOR HLTH SCIS · PI Anthony W Ferrante, DYMPNA GALLAGHER · 1986 to 2026
$33.0M
Translational Research CoreP30DK020541 · NIDDK · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI STREAMSON C CHUA · 2015 to 2026
$27.7M
Core-010UL1TR001073 · NCATS · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI KELLER, MARLA J, SHAMOON, HARRY · 2013 to 2017
$21.3M
Einstein's Nathan Shock Center of Excellence in Basic Biology of AgingP30AG038072 · NIA · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI HUFFMAN, DEREK MAJOR · 2010 to 2024
$10.8M
The Role of the Glucose-regulated Protein GRP78/BiP in Stress Resistance and AginP01AG034906 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI MITCHELL, JAMES R. · 2011 to 2016
$9.3M
Dysregulation of Glucose Homeostasis in AgingR37AG018381 · NIA · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI BARZILAI, NIR J · 2010 to 2019
$3.5M
Novel Mitochondrially Encoded Peptides and Their Role in Health and DiseaseR01GM090311 · NIGMS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI COHEN, PINCHAS · 2009 to 2013
$3.2M
Plasma Mitochondrial Peptide Assays as Biomarkers of Environmental Toxin ExposureR01ES020812 · NIEHS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI COHEN, PINCHAS · 2011 to 2015
$1.8M
Novel Regulators of Glucose Homeostasis in AgingR01AG035114 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MUZUMDAR, RADHIKA HIREN · 2010 to 2014
$1.6M
CNS/IGF-axis in modulation of body composition in agingK08AG027462 · NIA · MONTEFIORE MEDICAL CENTER (BRONX, NY) · PI MUZUMDAR, RADHIKA HIREN · 2007 to 2011
$747k
Peripheral and central IGF-1 action in energy balance and longevity modulation R00AG037574 · NIA · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI HUFFMAN, DEREK MAJOR · 2013 to 2015
$732k
NCATS NIH HHS UL1 TR001073NIA NIH HHS K08 AG027462NIA NIH HHS P01 AG034906NIA NIH HHS P30 AG038072NIA NIH HHS R00 AG037574NIA NIH HHS R01 AG035114NIA NIH HHS R37 AG018381NIDDK NIH HHS P30 DK020541NIDDK NIH HHS P30 DK026687NIEHS NIH HHS R01 ES020812NIGMS NIH HHS R01 GM090311
6 · The paper itself

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.

Indexed as

3T3-L1 CellsAnimalsApoptosisCell DifferentiationCell LineDNA, MitochondrialHumansInsulin ResistanceIntracellular Signaling Peptides and ProteinsMiceMitochondriaPeptidesDNA, MitochondrialhumaninIntracellular Signaling Peptides and ProteinsPeptidesaginghumaninmitochondriaSHLPsmall ORFs

Identifiers

PMID27070352
PMCPMC4925829
OpenAlexW2396191679

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.