Recurrent turnover of senescent cells during regeneration of a complex structure.
Cellular senescence has been recently linked to the promotion of age-related pathologies, including a decline in regenerative capacity. While such capacity deteriorates with age in mammals, it remains intact in species such as salamanders, which have an extensive repertoire of regeneration and can undergo multiple episodes through their lifespan. Here we show that, surprisingly, there is a significant induction of cellular senescence during salamander limb regeneration, but that rapid and effective mechanisms of senescent cell clearance operate in normal and regenerating tissues. Furthermore, the number of senescent cells does not increase upon repetitive amputation or ageing, in contrast to mammals. Finally, we identify the macrophage as a critical player in this efficient senescent cell clearance mechanism. We propose that effective immunosurveillance of senescent cells in salamanders supports their ability to undergo regeneration throughout their lifespan.
Institute of Structural and Molecular Biology, Division of Biosciences, University College London, London, United Kingdom.
Maximina H
MH
Yun
Institute of Ophthalmology, University College London, London, United Kingdom.
Hongorzul
H
Davaapil
Institute of Structural and Molecular Biology, Division of Biosciences, University College London, London, United Kingdom.
Jeremy P
JP
Brockes
D000375:Aging / Q000502:physiology*; D000818:Animals; D024201:Bystander Effect; D016923:Cell Death; D049109:Cell Proliferation; D016922:Cellular Senescence / Q000502:physiology; D005121:Extremities / Q000293:injuries / Q000502:physiology; D007157:Immunologic Surveillance / Q000502:physiology; D008264:Macrophages / Q000166:cytology* / Q000276:immunology; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D010587:Phagocytosis; D061251:Primary Cell Culture; D012038:Regeneration / Q000502:physiology*; D014562:Caudata / Q000502:physiology*; D014945:Wound Healing / Q000502:physiology*
ageing; axolotl; cell biology; developmental biology; macrophage; newt; salamander; senescence; stem cells