Senescence-induced cellular reprogramming drives cnidarian whole-body regeneration
Abstract
Cell fate stability is essential to maintaining “law and order” in complex animals. However, high stability comes at the cost of reduced plasticity and, by extension, poor regenerative ability. This evolutionary trade-off has resulted in most modern animals being rather simple and regenerative or complex and non-regenerative. The mechanisms mediating cellular plasticity and allowing for regeneration remain unknown. We show that signals emitted by senescent cells can destabilize the differentiated state of neighboring somatic cells, reprogramming them into stem cells that are capable of driving whole-body regeneration in the cnidarian Hydractinia symbiolongicarpus. Pharmacological or genetic inhibition of senescence prevents reprogramming and regeneration. Conversely, induction of transient ectopic senescence in a regenerative context results in supernumerary stem cells and faster regeneration. We propose that senescence signaling is an ancient mechanism mediating cellular plasticity. Understanding the senescence environment that promotes cellular reprogramming could provide an avenue to enhance regeneration.
Related
- TRPM2-mediated Ca2+ entry drives cellular senescence to irradiation-induced salivary gland dysfunction
- Soluble pathogenic tau transmission to astrocytes drives acute oxidative damage, cellular senescence, and neurovascular uncoupling in a model of Alzheimers tauopathy
- The RNA-binding protein TRIM71 Promotes Supporting Cell Reprogramming and Hair Cell Regeneration by Activating Sall4
- Metabolic-Epigenetic Coupling in Cellular Senescence: In Silico Cristae Remodeling Depletes Alpha-Ketoglutarate to Drive KDM4/6 Inhibition and SASP Amplification
- Impaired Peroxisome Import Drives Cellular Senescence through SCAF1-Dependent Suppression of Mitoribosome Biogenesis
BibTeX
@article{salinassaavedra2026senescenceinduced,
title = {{Senescence-induced cellular reprogramming drives cnidarian whole-body regeneration}},
author = {Miguel Salinas-Saavedra and F. Febrimarsa and Gabriel Krasovec and Helen R Horkan and Andreas D Baxevanis and Uri Frank},
journal = {Cell Reports},
year = {2026},
month = oct,
doi = {10.1016/j.celrep.2023.112687},
url = {https://hal.science/hal-05775878v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Senescence-induced cellular reprogramming drives cnidarian whole-body regeneration
AU - Miguel Salinas-Saavedra
AU - F. Febrimarsa
AU - Gabriel Krasovec
AU - Helen R Horkan
AU - Andreas D Baxevanis
AU - Uri Frank
PY - 2026
DA - 2026/10/06
JO - Cell Reports
DO - 10.1016/j.celrep.2023.112687
UR - https://hal.science/hal-05775878v1
AB - Cell fate stability is essential to maintaining “law and order” in complex animals. However, high stability comes at the cost of reduced plasticity and, by extension, poor regenerative ability. This evolutionary trade-off has resulted in most modern animals being rather simple and regenerative or complex and non-regenerative. The mechanisms mediating cellular plasticity and allowing for regeneration remain unknown. We show that signals emitted by senescent cells can destabilize the differentiated state of neighboring somatic cells, reprogramming them into stem cells that are capable of driving whole-body regeneration in the cnidarian Hydractinia symbiolongicarpus. Pharmacological or genetic inhibition of senescence prevents reprogramming and regeneration. Conversely, induction of transient ectopic senescence in a regenerative context results in supernumerary stem cells and faster regeneration. We propose that senescence signaling is an ancient mechanism mediating cellular plasticity. Understanding the senescence environment that promotes cellular reprogramming could provide an avenue to enhance regeneration.
SN - 2211-1247
SN - 2211-1247
ER -