Evidence map›Paper›PMID 42834419›Full record

ArticleStem cell research & therapy2026

Senotherapeutic potential against xeroderma pigmentosum.

Xuebing Wang, Masako Nishida, Ai Yoshioka, Claire Yik-Lok Chung, Shinya Hashimoto, Hideki Tanizawa, Shinya Ohta, Ken-Ichi Noma, Takeshi Fukumoto

Abstract read
In one paragraph

Article in Stem cell research & therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

9 authors.

Xuebing WangInstitute for Genetic Medicine, Hokkaido University, Sapporo, 060-0815, Japan.
Masako NishidaDivision of Dermatology, Department of Internal Related, Graduate School of Medicine, Kobe University, Kobe, 650-0017, Japan.
Ai YoshiokaDivision of Dermatology, Department of Internal Related, Graduate School of Medicine, Kobe University, Kobe, 650-0017, Japan.
Claire Yik-Lok ChungInstitute for Genetic Medicine, Hokkaido University, Sapporo, 060-0815, Japan.
Shinya HashimotoDivision of Dermatology, Department of Internal Related, Graduate School of Medicine, Kobe University, Kobe, 650-0017, Japan.
Hideki TanizawaInstitute for Genetic Medicine, Hokkaido University, Sapporo, 060-0815, Japan.
Shinya OhtaInstitute for Genetic Medicine, Hokkaido University, Sapporo, 060-0815, Japan.
Ken-Ichi NomaInstitute for Genetic Medicine, Hokkaido University, Sapporo, 060-0815, Japan. noma@igm.hokudai.ac.jp.
Takeshi FukumotoDivision of Dermatology, Department of Internal Related, Graduate School of Medicine, Kobe University, Kobe, 650-0017, Japan. fukumoto@koto.kpu-m.ac.jp.

Funding

Japan Agency for Medical Research and Development 24ym0126809j0003Japan Science and Technology Agency SPRING JPMJSP2119Japan Society for the Promotion of Science JP20K23376Japan Society for the Promotion of Science JP25KJ0515
6 · The paper itself

Abstract

backgroundXeroderma pigmentosum (XP) is an inherited photoaging syndrome caused by mutations in genes involved in the nucleotide excision repair (NER) pathway. XP patients exhibit hypersensitivity to ultraviolet (UV) radiation, leading to accelerated skin aging and requiring lifelong sun avoidance. In this study, we aimed to investigate UV-induced cellular senescence in XP melanocytes and explore potential senotherapeutic strategies.

methodsMelanocytes differentiated from iPSCs derived from an XP-A patient and a healthy individual, respectively, were used to induce senescence. Senescence was assessed by SA-β-gal and γH2AX staining. The drug screening tested a panel of 12 senolytic agents and 15 senomorphic agents for their ability to target senescent XP-iMCs. The effects of these agents were evaluated through cell viability assays and SPiDER-βGal staining followed by flow cytometry. RNA sequencing was performed to analyze transcriptional changes induced by senomorphic treatments.

resultsWe demonstrate that UV-induced DNA damage triggers cellular senescence and up-regulates senescence-associated secretory phenotype (SASP) genes in melanocytes derived from an XP patient. The drug screening identified JAK inhibitors and curcuminoids as promising senomorphic agents. In addition, two classes of senolytic agents, BCL-2-like protein inhibitors and HSP90 inhibitors, effectively eliminate senescent melanocytes. Further analysis demonstrates that senomorphic treatment effectively counteracts senescence and reduces SASP gene expression in XP-derived melanocytes. Moreover, genes in senescence-related pathways, including the cytokine-cytokine receptor interaction, JAK/STAT, and PI3K/AKT pathways, which are activated in senescent cells, are down-regulated by senomorphic treatment.

conclusionsThis study highlights a potential senotherapeutic strategy for XP, which may help alleviate photoaging symptoms in XP patients.

Indexed as

MelanocytesSenotherapeuticsXeroderma PigmentosumCellular SenescenceDNA DamageHumansSenescence-Associated Secretory PhenotypeUltraviolet RaysSenotherapeuticsCellular senescencePhotoagingSenescence-associated secretory phenotypeSenolytic agentsSenomorphic agents

Identifiers

PMID42834419
PMCPMC13637285

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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.