Fight Aging! Newsletter, December 6th 2021

In this study, they found these drugs can kill senescent cells from cultures of human fat tissue. The tissue was donated by individuals with obesity who were known to have metabolic troubles. Without treatment, the human fat tissues induced metabolic problems in immune-deficient mice. After treatment with dasatinib and quercetin, the harmful effects of the fat tissue were almost eliminated. Targeting p21Cip1 highly expressing cells in adipose tissue alleviates insulin resistance in obesity Insulin resistance is a pathological state often associated with obesity, representing a major risk factor for type 2 diabetes. Limited mechanism-based strategies exist to alleviate insulin resistance. Here, using single-cell transcriptomics, we identify a small, critically important, but previously unexamined cell population, p21Cip1 highly expressing (p21high) cells, which accumulate in adipose tissue with obesity. By leveraging a p21-Cre mouse model, we demonstrate that intermittent clearance of p21high cells can both prevent and alleviate insulin resistance in obese mice. Exclusive inactivation of the NF-κB pathway within p21high cells, without killing them, attenuates insulin resistance. Moreover, fat transplantation experiments establish that p21high cells within fat are sufficient to cause insulin resistance in vivo. Importantly, a senolytic cocktail, dasatinib plus quercetin, eliminates p21high cells in human fat ex vivo and mitigates insulin resistance fol...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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