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Drug may limit damage from ageing

Wednesday October 20th 2021

Scientists have identified a method of selectively destroying cells in the body linked to ageing.

The process of senescence leads cells to deteriorate, in order to prevent damaged cells from proliferating. However, a build up of senescent cells over time is linked to functional impairment of organs as seen in ageing.

This build up is also associated with fibrosis and tumour progression, and may be linked to cataracts, obesity, diabetes, Alzheimer’s and Parkinson’s diseases, arthritis, atherosclerosis and many other age-related conditions.

Dr Salvador Macip, of the University of Leicester, UK, and colleagues investigated the impact of senescence. In Scientific Reports, they suggest that it has "beneficial effects in the early decades of life, but is detrimental to fitness and survival at later stages, after the percentage of senescent cells in tissues reaches a critical threshold."

They developed a way to clear senescent cells from tissues, with the aim of prolonging lifespan and 'healthspan', using a new class of drugs called senolytics.

Previous work found that senolytics were not effective and carried side-effects, so the team tried a targeted approach on a cell membrane marker of senescence.

In lab tests, their antibody-drug combination clears senescent cells by releasing a cytotoxin into them, leaving non-senescent cells unaffected.

"Our results provide a proof-of-principle assessment of a novel approach for the specific elimination of senescent cells using a second generation targeted senolytic against proteins of their surfaceome, which could have clinical applications in pathological ageing and associated diseases," they write.

Dr Macip said: “Copying an idea already in use in cancer therapies, we tweaked an antibody so it could recognise these cells and deliver a toxic cargo specifically into them.”

Poblocka, M. et al. Targeted clearance of senescent cells using an antibody-drug conjugate against a specific membrane marker. Scientific Reports 13 October 2021; doi: 10.1038/s41598-021-99852-2

[abstract]

Tags: General Health | Pharmaceuticals | UK News

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