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Reactions to a study published in Nature that show a causal link between the accumulation of senescent cells and cognitive neuronal loss in mice.
Dr Rosa Sancho, Head of Research at Alzheimer’s Research UK, said:
“Researchers are continuing to build a clearer picture of the precise interplay between the immune system and the brain, and this new work adds another piece to this puzzle.
“In this small but well-designed mouse study, researchers were able to clear faulty immune cells from a region of the brain important for memory and thinking, and that doing so could limit damage associated with neurodegenerative diseases.
“As this study cleared toxicity using genetic techniques in mice, further efforts are needed to explore how this approach could be translated into a treatment that could be tested in people. There are many hurdles to overcome in developing treatments for neurodegenerative diseases, targeting these cell types could be a promising approach but is still some way off benefitting people living with dementia.”
Prof Lawrence Rajendran, Deputy Director of the Dementia Research Institute, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, said:
“This is an exciting study – as it is not only novel in its approach but also opens up new vistas for both diagnosis and therapy for neurodegenerative diseases, including Alzheimer’s.
“However, we need to exercise caution as to not over-interpret its relevance to dementia in humans as the study was performed in a mouse model of dementia and also that this study needs to be replicated. Nevertheless, this study shows promise for alternative ways to tackle the disease which has been so far difficult using traditional approaches. Though the word “Neurodegeneration” implies a “neuro” centricity in the disease which has steered our translational approaches to target exclusively neuronal mechanisms, it is increasingly becoming clear that other brain cells including astrocytes and microglia play defining roles. Last year, my lab showed that aberrant microglial cells in the brain without any perturbations in neuronal cells could still result in neurodegeneration encouraging us now to target these alternative mechanisms as therapeutic drug targets”
Prof Lorna Harries, Associate Professor in Molecular Genetics, University of Exeter, said:
“It is now becoming apparent that during the ageing process, cells can undergo a process called senescence, whereby they stop dividing, cease working as they should, and start to produce a cocktail of chemical signals that affect the function of other cells nearly. The idea that the build-up of senescent cells may contribute to age-related diseases such as dementia, diabetes and cardiovascular disease is now gaining ground amongst the scientific community.
“The authors of this well conducted study show in mouse models that senescent cells build up in the same regions of the brain that are involved in memory and cognition. Importantly, it is not the nerve cells themselves that become senescent, but the support cells that allow nerve cells to survive. Using a strain of mice that has been genetically altered to demonstrate early ageing, but importantly allows targeted destruction of senescent cells, removal of the senescent cells is able to bring about reversal of the microscopic changes in the brain. Not only this, the removal of the senescent cells is able to bring about reversal of the microscopic changes in the brain and also improves performance in memory and cognition tests in the mice involved. Some of the same changes were also observed using a chemical, rather than a genetic removal of senescent cells which means that similar approaches may one day bear fruit in the clinic without the need for genetic manipulation.
“These are exciting findings and the conclusions are well supported by data. They fit well with earlier data suggesting that removal of senescent cells in other systems is able to reverse other features of ageing. It must be remembered however that these results are from animal models genetically engineered to age faster and to allow targeted removal of senescent cells, and that these observations may not be so easy to reproduce in people with dementia. We are still a long way from the clinic, but we are a step closer.”
Dr James Pickett, Head of Research at Alzheimer’s Society, said:
“There hasn’t been a new dementia drug in 15 years so it’s exciting to see the results of this promising study in mice. However, there are several barriers to overcome before we can say if this is a safe, effective treatment in people. For example, we don’t know if this drug is actually able to enter the brain, and older people often have lots of harmless brain cells that look like the senescent ‘zombie’ cells this drug targets, so any treatment would have to be good at telling the two apart.
“These ‘zombie’ cells may increase the toxicity of tau, a damaging chemical that builds up in people with Alzheimer’s disease – so it’s a clever idea to target them with drugs. We urgently need to find a cure for the 850,000 people in the UK currently living with dementia, so we’ve invested nearly £3m in studies to better understand how tau affects the brain and work out how to reduce its toxicity.”
Output on this subject can be seen at this weblink: http://www.sciencemediacentre.org/tag/dementia
Declared interests
Dr Rosa Sancho: No conflicts of interest.
Prof Lorna Harries: I work on ways of removing senescent cells – I have IP (a patent) around this area, and am currently setting up a spin out company to explore ways of eventually removing senescent cells in the clinic, but this does not overlap at all with the work presented here. I have never met the authors of the study but have been following their work with interest.