The pursuit of a scientific fountain of youth has seen billions poured into the discovery of novel drug targets that may one day allow humans to pass their biological limits of age, whether that be re-inventing commonly-used drugs that may have anti-aging properties, or artificial intelligence screening millions of new drug candidates for the golden ticket to everlasting life.
Now, researchers from the University of Leicester believe their answer could be the ticket, and it shows no mercy for aging. By using antibodies that attack aging cells in the body and remove them, their therapy could help fight against the degenerative effects of aging and the diseases associated with it.
Their research has been published in Scientific Reports.
The new therapy builds on an existing class of drugs called senolytics, which have shown promise in clearing senescent (aging) cells but cause offsite problems elsewhere in the body, and so have not seen clinical use to date. To be viable, senolytics must be targeted towards senescent cells whilst leaving healthy cells unaffected.
To that end, senior author Salvador Macip and colleagues, in collaboration with researchers from Spain, Nigeria, and Saudi Arabia, designed an antibody-drug conjugate (ADC) that targets a membrane marker found on aging cells. The marker, called B2M, was recently identified as an indicator of senescence in cells, and poses a promising option for targeted senolytics.
Once the antibody binds to the marker, the cytotoxic drug duocarmycin would be released into the cell, resulting in cell death.
When tested on human cell lines, the antibody was specific for senescent cells and left normal cells unharmed, demonstrating a proof-of-concept that the ADC could be specific for the target aging cells.
“Senolytics are a new class of drugs with great potential to ameliorate ageing. However, the ones we have found so far are quite unspecific and thus may have strong side effects. That is why there is much interest in a second generation of drugs, the targeted senolytics, which should eliminate senescent cells without affecting the rest,” said Professor Macip in a statement.
“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.”
The research stands as an early proof-of-concept for an antibody targeting approach to senolysis, and now requires further testing to fully identify the mechanisms involved and whether B2M remains a contestant for a senescence marker or whether other options require exploration.
