Recurrent turnover of senescent cells during regeneration of acomplex structure

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Abstract

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.

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Maximina H Yun

Institute of Structural and Molecular Biology, Division of Biosciences, University College London, London, United Kingdom

For correspondence
maximina.yun@ucl.ac.uk

Competing interests
The authors declare that no competing interests exist.
Hongorzul Davaapil

Institute of Ophthalmology, University College London, London, United Kingdom

Competing interests
The authors declare that no competing interests exist.
Jeremy P Brockes

Institute of Structural and Molecular Biology, Division of Biosciences, University College London, London, United Kingdom

Competing interests
The authors declare that no competing interests exist.

Ethics

Animal experimentation: All procedures for care and manipulation of adult newts (Notophthalmus viridescens) and axolotls (Ambystoma mexicanum) were performed in compliance with the Animals (Scientific Procedures) Act 1986, approved by the United Kingdom Home Office and University College London (Institutional License: 70-2716). All surgical procedures were carried out under anesthesia (0.1% Tricaine) followed by treatment with analgesics (Butorphanol tartrate). Every effort was made to minimise suffering.

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This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.