Publications by authors named "K Kirschner"

Cellular senescence is not only associated with ageing but also impacts physiological and pathological processes, such as embryonic development and wound healing. Factors secreted by senescent cells affect their microenvironment and can induce spreading of senescence locally. Acute severe liver disease is associated with hepatocyte senescence and frequently progresses to multi-organ failure.

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The emergence of epigenetic predictors was a pivotal moment in geroscience, propelling the measurement and concept of biological aging into a quantitative era; however, while current epigenetic clocks show strong predictive power, they are data-driven in nature and are not based on the underlying biological mechanisms driving methylation dynamics. We show that predictions of these clocks are susceptible to several confounding non-age-related phenomena that make interpretation of these estimates and associations difficult. To address these limitations, we developed a probabilistic model describing methylation transitions at the cellular level.

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Article Synopsis
  • Cancer-associated fibroblasts (CAFs) in B-cell precursor acute lymphoblastic leukemia (B-ALL) originate from bone marrow-derived mesenchymal stromal cells (MSCs) and are influenced by reactive oxygen species from chemotherapy.
  • The study shows that exposure of MSCs to B-ALL cells or their secretions initiates the CAF formation, marked by a strong interferon pathway response.
  • A key finding is that leukemia cell-derived mitochondrial double-stranded RNA (dsRNA) stimulates MSCs to transition into CAFs, and disrupting dsRNA can block this process, revealing a new way cancer cells interact with their environment.
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Introduction: Congenital anomalies of the kidney and urinary tract (CAKUT) represent the most common cause of chronic kidney disease in children. Although only 20% of cases can be genetically explained, the majority remain without an identified underlying etiology. The neurodevelopmental disorder Chung-Jansen syndrome (CHUJANS) is caused by haploinsufficiency of Pleckstrin homology domain-interacting protein (PHIP) and was previously associated with genital malformations.

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