Biology subjects

Ritschka, B.

Publications and source records attributed to Ritschka, B..

3 recordsLinked to original sources

bioRxiv2026

Senescence targeting re-enables injury-responsive repair in a human RPE aging model

Aging is associated with progressive tissue dysfunction and impaired repair after injury. In the retinal pigment epithelium (RPE), these changes contribute to age-related macular degeneration (AMD), yet the mechanisms limiting repair remain incompletely understood. Here, we establish a longitudinal human embryonic stem cell (hESC)-derived RPE aging model that recapitulates key features of aged human donor RPE and combine it with mosaic cell ablation to assess injury-responsive repair. Although aged RPE cells initiate DNA synthesis after injury, they exhibit impaired mitotic progression, uncoupling S-phase entry from epithelial repopulation. Transcriptomic profiling links this defect to a senescence-associated program marked by inflammatory signaling and suppressed mitotic networks. Pharmacologic reduction of senescent cells with Navitoclax shifts aged RPE toward a younger transcriptional profile but does not induce repopulation by itself. Instead, senolytic treatment primes aged RPE for repair, improving epithelial density and homeostatic function only in response to injury, a strategy we term "senolytic priming." These findings establish a human stem-cell-derived platform for investigating age-associated epithelial repair failure and show that aged human RPE retains latent repair capacity that can be re-enabled by targeting cellular senescence.

Cell Biology↗

bioRxiv2025

Senescent cells exhibit features of developmental signaling centres

Cellular senescence is a state that contributes to tissue patterning during development and tissue repair, but which becomes misregulated in ageing and disease. The senescence-associated secretory phenotype (SASP) mediates many of the context-dependent effects, yet its molecular composition and evolutionary origins remain incompletely understood. Here, we characterize the SASP signature of developmental senescent cells and find that it is enriched for genes encoding major developmental signaling pathways. Integrative analyses of in vitro and in vivo transcriptomes reveal that human and mouse senescent cells across diverse contexts consistently activate these developmental programs, with key morphogens constituting conserved SASP components. Functionally, we show that the SASP is sufficient to induce the expression of central developmental genes and transcription factors across multiple cell types. These findings show that senescent cells resemble developmental signaling centers and uncover developmental signaling reactivation as an evolutionarily conserved feature of senescence, providing conceptual insight into its physiological functions and its pathological impact during ageing.

cell biology↗

bioRxiv2019

Senolytic treatment targets aberrant p21-expression to restore liver regeneration in adult mice

Young mammals possess a limited regenerative capacity in tissues such as the liver, heart and limbs, but which is quickly lost upon maturation or transition to adulthood. Chronic cellular senescence is a known mediator of decreased tissue function in aging and disease. Here we investigated whether senescence plays a role in the progressive loss of liver regenerative capacity that develops in young adult mice. We find that following partial hepatectomy, the senescence markers p21, p16Ink4a and p19Arf become dynamically expressed at an age when regenerative capacity decreases. In addition, we demonstrate that treatment with a senescence-inhibiting drug improves regenerative capacity, through targeting of aberrant p21 expression. Surprisingly, we also find that the senescence marker p16Ink4a is expressed in a different cell-population to p21, and is unaffected by senescence targeting. This work suggests that senescence may initially develop as a heterogeneous cellular response, and that treatment with senolytic drugs may aid in promoting organ regeneration.

cell biology↗