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Insights into CNS ageing from animal models of senescence

Abstract

In recent years, novel model systems have made significant contributions to our understanding of the processes that control the ageing of whole organisms. However, there are limited data to show that the mechanisms that gerontologists have identified as having a role in organismal ageing contribute significantly to the ageing of the central nervous system. Two recent discoveries illustrate this particularly well. The first is the consistent failure of researchers to demonstrate a simple relationship between organismal ageing and oxidative stress — a mechanism often assumed to have a primary role in brain ageing. The second is the demonstration that senescent cells play a causal part in organismal ageing but remain essentially unstudied in a CNS context. We argue that the animal models now available (including rodents, flies, molluscs and worms), if properly applied, will allow a paradigm shift in our current understanding of the normal processes of brain ageing.

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Figure 1: Schematic representation of the putative effects of the major ageing mechanisms on the CNS.
Figure 2: Schematic representation of the age-related changes to hippocampal neuronal biophysics.
Figure 3: Schematic representations of the proposed interaction between ROS, mTOR and FK506bp and neuronal ageing in rat hippocampal neurons.

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Acknowledgements

The authors gratefully acknowledge the financial support of the Glenn Foundation, Research Into Ageing and the Biotechnology and Biological Sciences Research Council (G015147/1).

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Yeoman, M., Scutt, G. & Faragher, R. Insights into CNS ageing from animal models of senescence. Nat Rev Neurosci 13, 435–445 (2012). https://doi.org/10.1038/nrn3230

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