Senolytic Treatment Fails to Reverse Uterine Fibrosis in Mice

Senolytic drugs that selectively destroy senescent cells in aged tissues have performed quite well in animal studies of fibrosis in heart, lung, and kidney. The therapy reverses fibrosis in those tissues to a larger degree, and with greater reliably, than is the case for any other readily available approaches. Unfortunately small molecule senolytics are all tissue specific to varying degrees in their biodistribution and effects, and so the benefits are not universally realized throughout the body. As an example of this point, researchers here show that uterine fibrosis and its consequences are unresponsive to dasatinib and quercetin senolytic treatment, though they do not determine whether the compounds reach the uterus to the same degree as is the case for the heart, lung, or kidneys. That leaves the question of exactly why this treatment is ineffective, poor biodistribution of the senolytics versus tissue-specific mechanistic differences in cellular senescence and fibrosis, to be answered at a later date. The most obvious histological change in the aged uterus is the collagen deposition (fibrosis) in the muscle layers and stroma. Mechanisms involved in this uterine fibrosis remain unclear. Collagen deposition in tissues occurs as a result of chronic inflammatory processes involving several pathways: inflammatory interleukins, growth factors, caspases, oxidative stress products, and accumulation of senescent cells. Targeting senescent cells with senolytic dru...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs