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Drug targeting old cells reverses ageing in mice

27 March 2017
Appeared in BioNews 894

A drug that reverses aspects of ageing has been successfully demonstrated in mice.

The drug, made from a protein peptide, selectively destroys senescent cells, which are old cells which have stopped dividing and release chemicals implicated in the ageing process.

'Only in senescent cells does this peptide cause cell death,' said senior author Dr Peter de Keizer, a researcher of ageing at Erasmus University Medical Center in the Netherlands. 'We treated mice for over 10 months, giving them infusions of the peptide three times a week, and we didn't see any obvious side effects.'

As they age, the body's cells accumulate DNA damage and eventually cannot be repaired. At this point cells can become cancerous, self-destruct, or enter a semi-dormant stage called 'senescence'. Although senescent cells were once thought to be harmless, and have useful functions such as a role in wound healing, research has increasingly indicated they are implicated in age-related diseases including arthritis and cataracts.

'It was found that these senescent cells secrete a whole load of junk and they're not just bystanders but have a negative effect,' said Dr de Keizer to the Guardian.

A previous study by a different team had shown that removing senescent cells could extend the lifespan of mice by a fifth on average. Now in a new study published in Cell, scientists at Erasmus University Medical Center in the Netherlands have shown that ageing in mice can be slowed and even reversed by removing senescent cells.

The scientists developed a peptide compound to trigger cell death specifically in senescent cells. They tested this peptide, called FOXO4-DRI, in groups of naturally aged mice and mice which had been rapidly aged using genetically engineering or chemotherapy, giving them doses of the drug three times a week for 10 months.

After 10 days, the scientists found the genetically engineered mice had begun to regrow missing fur, and at three weeks their fitness had improved. After four weeks, naturally and artificially aged mice also showed improved kidney and liver function, and cell senescence related to chemotherapy had been reduced.

The team next plan to test the drug in a human clinical trial with patients with an aggressive form of brain tumour, where the cancerous cells feature a similar marker to those found in senescent cells and so may be vulnerable to the drug.

'The development of drugs, which interfere with the causes of ageing and improve health and fitness are a relatively new area of research and have the potential to change the way we treat diseases of older people and keep people healthy for longer,' said Professor Ilaria Bellantono of the University of Sheffield, who was not involved in the study. The drug appeared more 'potent' than previously tested drugs, but she added that the effects of the drug on different tissues of the body need to be studied in detail, as would whether the drug interferes with the efficacy of chemotherapy.

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