同济大学学报(医学版)2025,Vol.46Issue(5):677-689,13.DOI:10.12289/j.issn.2097-4345.25049
2型糖尿病小鼠骨组织中p21与p16相关衰老的时空异质性研究
Heterogeneity and temporal asynchrony of p21-and p16-associated senescence in bone tissue of type 2 diabetic mouse model
摘要
Abstract
Objective Based on the distinct expression characteristics of p16 and p21,the most widely used markers in cellular senescence research,this study explored the heterogeneity and temporal asynchrony of senescence in bone and adipose tissues in a type 2 diabetic mouse model,and compared therapeutic efficacy of various anti-aging strategies.Methods A p21-3MR mouse model was used to establish a type 2 diabetes model.The senescence patterns in bone tissue of type 2 diabetic mice were analyzed using the femur as an example,with a focus on the heterogeneity and temporal asynchrony of p16 and p21 during the progression of diabetes.The anti-aging effects of quercetin combined with dasatinib(D+Q)and p21-specific intervention were evaluated.Results The results revealed significant heterogeneity and asynchrony in aging of cortical bone and bone marrow during the progression of diabetes,with bone marrow aging predominantly associated with p21 and occurring at an earlier stage,while cortical bone aging was closely related to the expression of p16.Different treatments exhibited distinct effects in bone marrow and cortical bone,with D+Q showing superior efficacy in critical bone,whereas p21-specific intervention demonstrated significant effects in bone marrow.These findings provide new insights into the intervention of bone aging in diabetes.Conclusion The aging heterogeneity between cortical bone and bone marrow tissue is significant,and different treatment methods each have their own distinct characteristics.关键词
2型糖尿病/细胞衰老/衰老异质性/衰老异步性/p21/p16Key words
type 2 diabetes mellitus/cellular senescence/heterogeneous aging/asynchronous aging/p21/p16分类
医药卫生引用本文复制引用
严家玉,是佳滢,陈思艺,赵若闻,吴珺华..2型糖尿病小鼠骨组织中p21与p16相关衰老的时空异质性研究[J].同济大学学报(医学版),2025,46(5):677-689,13.基金项目
上海市"科技创新行动计划"自然科学基金项目(23ZR1469100) (23ZR1469100)
上海市科学技术委员会实验动物基金项目(23141902500) (23141902500)