Evidence map›Paper›PMID 42045911›Full record

ArticleJournal of biomedical science2026

Phosphatidylinositol transfer protein-1 integrates insulin/IGF-1 and TOR signaling to negatively regulate lifespan and healthspan in Caenorhabditis elegans.

Yen-Hung Lin, Yun-Hsun Liao, Sin-Bo Liao, Tzu-Yu Lin, Muniesh Muthaiyan Shanmugam, Pei-Jia Hsu, Chang-Shi Chen, Tsiu-Ting Ching, Oliver Ingvar Wagner, Chiou-Hwa Yuh and 1 more

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In one paragraph

Article in Journal of biomedical science, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
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1 · What the graph read from it

What it found

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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

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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

1 citing paper in PubMed.

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4 · The record

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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

11 authors.

Yen-Hung LinInstitute of Biotechnology, National Tsing Hua University, Hsinchu, 300044, Taiwan.
Yun-Hsun LiaoInstitute of Biotechnology, National Tsing Hua University, Hsinchu, 300044, Taiwan.
Sin-Bo LiaoInstitute of Biotechnology, National Tsing Hua University, Hsinchu, 300044, Taiwan.
Tzu-Yu LinInstitute of Biotechnology, National Tsing Hua University, Hsinchu, 300044, Taiwan.
Muniesh Muthaiyan ShanmugamInstitute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu, 300044, Taiwan.
Pei-Jia HsuDepartment of Life Science, National Tsing Hua University, Hsinchu, 300044, Taiwan.
Chang-Shi ChenDepartment of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Tsiu-Ting ChingInstitute of Biopharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, 112304, Taiwan.
Oliver Ingvar WagnerInstitute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu, 300044, Taiwan.
Chiou-Hwa YuhInstitute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, 300044, Taiwan. chyuh@nhri.edu.tw.
Horng-Dar WangInstitute of Biotechnology, National Tsing Hua University, Hsinchu, 300044, Taiwan. hdwang@life.nthu.edu.tw.

Funding

National Science and Technology Council 108-2311-B-007-007 ;109-2311-B-007-002 ;110-2320-B-007-003-; 111-2320-B-007-006-MY3, 114-2320-B-007-002-National Science and Technology Council 111-2320-B-400-018-MY3; 114-2320-B-400-022-MY3
6 · The paper itself

Abstract

backgroundPhosphatidylinositol transfer protein-1 (pitp-1) is involved in the phosphoinositide (PIP) cycle. The role of pitp-1 in promoting healthy longevity remains unknown. Our previous work showed that the PIP cycle-related genes diacylglycerol lipase-1 (dagl-1) and diacylglycerol kinase-5 (dgk-5) regulate lifespan, as overexpression of dagl-1 or knockdown of dgk-5 prolongs lifespan and enhances oxidative stress resistance through target of rapamycin (TOR) signaling. As pitp-1 is a key component of this pathway, we investigated its role in lifespan regulation and the underlying mechanisms, aiming to clarify whether it represents a critical regulator of healthy longevity and how it coordinates conserved signaling pathways to regulate aging.

methodsCaenorhabditis elegans (C. elegans) mutants, RNAi-mediated knockdown, and transgenic overexpression were applied to assess lifespan, motility, and stress resistance. Temporal and tissue-specific RNAi were applied to identify critical time window and tissue for pitp-1-mediated lifespan regulation. TOR signaling was measured by phosphorylated S6 kinase (p-S6K) and puromycin incorporation, and transcriptomic analysis identified affected pathways.

resultspitp-1 negatively regulated lifespan and healthspan in C. elegans. Genetic deletion or RNAi-mediated knockdown of pitp-1 extended lifespan, attenuated age-related motility decline, and increased oxidative stress resistance. Temporal and spatial analyses revealed that suppression of pitp-1 in neurons during early adulthood was sufficient to promote healthy longevity. Mechanistically, these beneficial effects upon pitp-1 reduction were associated with suppression of TOR signaling. Conversely, pitp-1 overexpression shortened lifespan and impaired healthspan via TOR activation. Moreover, pitp-1 was transcriptionally repressed by DAF-16 downstream of insulin/IGF-1 signaling (IIS), and contributed to IIS-mediated longevity regulation. Furthermore, pitp-1 reduction also improved organismal proteostasis, as evidenced by decreased polyglutamine (polyQ) aggregation and enhanced motility in a neuronal proteotoxicity model.

conclusionsThese findings identify pitp-1 as a novel regulator of healthy aging, suggesting a role in coordinating IIS and TOR signaling and providing new insights into conserved mechanisms of longevity regulation.

Indexed as

Caenorhabditis elegansCaenorhabditis elegans ProteinsInsulinInsulin-Like Growth Factor ILongevityPhospholipid Transfer ProteinsSignal TransductionTOR Serine-Threonine KinasesAnimalsCaenorhabditis elegans ProteinsInsulinInsulin-Like Growth Factor IPhospholipid Transfer ProteinsTOR Serine-Threonine KinasesAgingCaenorhabditis elegansHealthspanInsulin/igf-1 signalingLongevityPitp-1TOR signaling

Identifiers

PMID42045911
PMCPMC13112645

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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.