Senescence and sinotherapy in biliary atresia and biliary cirrhosis

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image: Figure 2. Cholangiocytes and perinodular hepatocytes show cellular senescence in BA livers.
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Credit: 2023 Jannone et al.

“Our data provide the first supplementary report on premature senescence in pediatrics [biliary atresia] […]”

BUFFALO, NY – June 282023 – A new research paper has been published in Aging (listed by MEDLINE/PubMed as “Aging (Albany NY)” and “Aging-US” by Web of Science) Volume 15, Number 11titled, “Senescence and sinotherapy in biliary atresia and biliary cirrhosis.”

Premature senescence occurs in adult hepatobiliary disease and worsens prognosis through deleterious liver remodeling and liver dysfunction. Senescence could also arise in biliary atresia (BA), the leading cause of pediatric liver transplantation. Alternatives to transplant are needed. In this new study, the researchers Giulia Jannone, Eliano Bonaccorsi Riani, Catherine de Magnée, Roberto Tambucci, Jonathan Evraerts, Joachim Ravau, Pamela Baldin, Caroline Bouzin, Axelle Loriot, Laurent Gatto, Anabelle Decottignies, Mustapha Najimi, AND Etienne Marc Sokal from the Catholic University of Louvain in Brussels, Belgium, aimed to study premature senescence in BA and to evaluate breast therapies in a preclinical model of biliary cirrhosis.

“Since novel therapies are needed to avoid or delay liver transplantation in pediatric biliary cirrhosis, the aim of our work was to investigate premature senescence in BA through a multitechnique approach and evaluate sinotherapies in a preclinical model of biliary cirrhosis.

BA liver tissues were prospectively obtained at hepatoportoenterostomy (n = 5) and liver transplantation (n = 30) and compared with controls (n = 10). Senescence was studied through spatial analysis of the whole transcriptome, SA-β-gal activity, p16 and p21 expression, γ-H2AX, and senescence-associated secretory phenotype (SASP). Allogeneic human liver-derived progenitor cells (HALPCs) or dasatinib and quercetin (D+Q) were administered to two-month-old Wistar rats after bile duct ligation (BDL).

Advanced premature senescence was evidenced in BA livers from the early stage and continued to progress until liver transplantation. Senescence and SASP were predominant in cholangiocytes, but were also present in surrounding hepatocytes. HALPC but not D+Q reduced the early senescence marker p21 in BDL rats and improved biliary damage (serum expression of γGT and Sox9) and hepatocyte mass loss (Hnf4a).

“BA livers showed advanced cellular senescence at diagnosis that continued to progress until liver transplantation. HALPC reduced premature senescence and ameliorated liver disease in a preclinical model of BA, providing encouraging preliminary results on the use of sinotherapy in pediatric biliary cirrhosis.

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Corresponding author: Julia Jannone

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Keyword: senescence, sinotherapy, liver, biliary cirrhosis, biliary atresia

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From Aging-USA:

Launched in 2009, Aging publishes articles of general interest and biological significance in all fields of aging and age-related disease research, including cancer, and now, with a special focus on the vulnerability of COVID-19 as an age-dependent syndrome. Topics in Aging go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathologies in model organisms, signal transduction pathways (eg, p53, sirtuins, and PI-3K/AKT /mTOR, among others) and approaches to modulating these signaling pathways.

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