The accumulation of senescent cells within tissues is thought to play an important role in the ageing process. Senescence is a state in which cells stop dividing, typically in response to DNA damage, and can enter an inflammatory state that is linked to many age-related diseases.
Animal experiments have shown that senolytics – therapies that target and eliminate senescent cells – are effective at treating multiple age-related diseases (such as osteoarthritis) and extending lifespan. Indeed, animal data has been remarkably strong, and has encouraged some researchers to progress tentatively to phase 1 trials in humans.
While these trials focus primarily on safety, they have already yielded some promising results. Oral dasatinib and quercetin appeared to improve the condition of idiopathic pulmonary fibrosis patients in one study, and seemed to effectively clear senescent cells in patients with diabetes-related kidney disease in research published last September. Meanwhile, a trial of UBX0101 injection suggests it may improve joint function for osteoarthritis patients.
These trials are cause for optimism: no safety problems have been encountered, and phase two trials have been approved for both therapies. Caution must still be exercised, as phase 1 trials are, by design, very small, and problems may emerge when a larger number of people are treated. However, the researchers involved argue that the local injection of UBX0101 makes serious side effects unlikely, while dasatinib and quercetin already have a good safety record.
There are plans to trial senolytic treatments in Alzheimer’s disease and macular degeneration and, later on, to see if age-related decline can be delayed in healthy individuals with high levels of senescent cells.
More information on the research discussed here, as well as the history of senescence and senolytics in general, can be found here: https://www.the-scientist.com/features/can-destroying-senescent-cells-treat-age-related-disease–67136
Can Destroying Senescent Cells Treat Age-Related Disease?: https://www.the-scientist.com/features/can-destroying-senescent-cells-treat-age-related-disease--67136
UNITY BIOTECHNOLOGY REPORTS PROMISING TOPLINE DATA FROM PHASE 1 FIRST-IN-HUMAN STUDY OF UBX0101 IN PATIENTS WITH OSTEOARTHRITIS OF THE KNEE: http://ir.unitybiotechnology.com/news-releases/news-release-details/unity-biotechnology-reports-promising-topline-data-phase-1-first
Kidney disease: Senescent cell burden is reduced in humans by senolytic drugs: https://www.sciencedaily.com/releases/2019/09/190918075729.htm
Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study: https://doi.org/10.1016/j.ebiom.2018.12.052
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