Evidence map›Paper›PMID 37828862›Full record

ArticleAging cell2023

Impaired mitophagosome-lysosome fusion mediates olanzapine-induced aging.

Xi Chen, Zhizhen Wang, Peng Zheng, Anjila Dongol, Yuanyi Xie, Xing Ge, Mingxuan Zheng, Xuemei Dang, Zehra Boz Seyhan, Nathan Nagaratnam and 2 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Aging cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 2 pooled it
2.8field-weighted citation impact, top 9% 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

11 citing papers in PubMed, 2 syntheses or guidelines pooled it, 13 citations in OpenAlex.

  1. Pooled it
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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

12 authors at 2 institutions in 2 countries.

Xi ChenSchool of Medical, Indigenous and Health Sciences, University of Wollongong, Wollongong, New South Wales, Australia.
Zhizhen WangSchool of Medical, Indigenous and Health Sciences, University of Wollongong, Wollongong, New South Wales, Australia.
Peng ZhengSchool of Medical, Indigenous and Health Sciences, University of Wollongong, Wollongong, New South Wales, Australia.
Anjila DongolSchool of Medical, Indigenous and Health Sciences, University of Wollongong, Wollongong, New South Wales, Australia.
Yuanyi XieSchool of Medical, Indigenous and Health Sciences, University of Wollongong, Wollongong, New South Wales, Australia.
Xing GeJiangsu Key Laboratory of Immunity and Metabolism, Jiangsu International Laboratory of Immunity and Metabolism, Department of Pathogen Biology and Immunology, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Mingxuan ZhengJiangsu Key Laboratory of Immunity and Metabolism, Jiangsu International Laboratory of Immunity and Metabolism, Department of Pathogen Biology and Immunology, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Xuemei DangJiangsu Key Laboratory of Immunity and Metabolism, Jiangsu International Laboratory of Immunity and Metabolism, Department of Pathogen Biology and Immunology, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Zehra Boz SeyhanSchool of Medical, Indigenous and Health Sciences, University of Wollongong, Wollongong, New South Wales, Australia.
Nathan NagaratnamSchool of Medical, Indigenous and Health Sciences, University of Wollongong, Wollongong, New South Wales, Australia.
Yinghua YuSchool of Medical, Indigenous and Health Sciences, University of Wollongong, Wollongong, New South Wales, Australia.
Xu-Feng HuangSchool of Medical, Indigenous and Health Sciences, University of Wollongong, Wollongong, New South Wales, Australia.ORCID 0000-0002-5895-2253
University of Wollongong · AUXuzhou Medical College · CN

Funding

Enhancing and expanding the CGC Strain CollectionP40OD010440 · OD · UNIVERSITY OF MINNESOTA · PI Ann E. Rougvie · 2012 to 2026
$7.5M
NIH HHS P40 OD010440
6 · The paper itself

Abstract

The lifespan of schizophrenia patients is significantly shorter than the general population. Olanzapine is one of the most commonly used antipsychotic drugs (APDs) for treating patients with psychosis, including schizophrenia and bipolar disorder. Despite their effectiveness in treating positive and negative symptoms, prolonged exposure to APDs may lead to accelerated aging and cognitive decline, among other side effects. Here we report that dysfunctional mitophagy is a fundamental mechanism underlying accelerated aging induced by olanzapine, using in vitro and in vivo (Caenorhabditis elegans) models. We showed that the aberrant mitophagy caused by olanzapine was via blocking mitophagosome-lysosome fusion. Furthermore, olanzapine can induce mitochondrial damage and hyperfragmentation of the mitochondrial network. The mitophagosome-lysosome fusion in olanzapine-induced aging models can be restored by a mitophagy inducer, urolithin A, which alleviates defective mitophagy, mitochondrial damage, and fragmentation of the mitochondrial network. Moreover, the mitophagy inducer ameliorated behavioral changes induced by olanzapine, including shortened lifespan, and impaired health span, learning, and memory. These data indicate that olanzapine impairs mitophagy, leading to the shortened lifespan, impaired health span, and cognitive deficits. Furthermore, this study suggests the potential application of mitophagy inducers as therapeutic strategies to reverse APD-induced adverse effects associated with accelerated aging.

Indexed as

Antipsychotic AgentsAgingAnimalsCaenorhabditis elegansHumansMitochondriaMitophagyOlanzapineAntipsychotic AgentsOlanzapineaccelerated agingantipsychoticscognitionhealth spanlifespanmitophagymitophagy inducerolanzapine

Identifiers

PMID37828862
PMCPMC10652317
OpenAlexW4387599240

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.