Regulation of Cellular Senescence in Type 2 Diabetes Mellitus: From Mechanisms to Clinical Applications

Abstract

Cellular senescence is accelerated by hyperglycemia through multiple pathways. Therefore, senescence is an important cellular mechanism to consider in the pathophysiology of type 2 diabetes mellitus (T2DM) and an additional therapeutic target. The use of drugs that remove senescent cells has led to improvements in blood glucose levels and diabetic complications in animal studies. Although the removal of senescent cells is a promising approach for the treatment of T2DM, two main challenges limit its clinical application: the molecular basis of cellular senescence in each organ is yet to be understood, and the specific effect of removing senescent cells in each organ has to be determined. This review aims to discuss future applications of targeting senescence as a therapeutic option in T2DM and elucidate the characteristics of cellular senescence and senescence-associated secretory phenotype in the tissues important for regulating glucose levels: pancreas, liver, adipocytes, and skeletal muscle.

The Effect of Long-Term Passage on Porcine SMCs’ Function and the Improvement of TGF-β1 on Porcine SMCs’ Secretory Function in Late Passage

“…Senescent cells begin to secrete a large number of inflammatory and proteolytic factors and appear a state of functional damage [53][54][55]. The research shows that TGF-β1 is also involved in regulating complex inflammation and generally considered to be an inhibitor of excessive inflammation [56][57][58].…”

Amide Alkaloids as Privileged Sources of Senomodulators for Therapeutic Purposes in Age-Related Diseases

“…33 Subsequent hyperglycemia has been shown to drive premature senescence of several cell types, including hepatocytes, pancreatic β cells, and adipocytes, by initiating a domino effect in which high production of mitochondrial ROS activates the p53-dependent DNA damage response and p16 INK4A pathways. 34 The use of senolytics in a mice model of type 2 DM has revealed beneficial effects, with a decrease of blood glucose levels. 34 Osteoarthritis is a degenerative disease of the skeletal system that can affect any joint of the body, leading to cartilage breakdown.…”

“…34 The use of senolytics in a mice model of type 2 DM has revealed beneficial effects, with a decrease of blood glucose levels. 34 Osteoarthritis is a degenerative disease of the skeletal system that can affect any joint of the body, leading to cartilage breakdown. 35 In the etiology of this pathology, chondrocytes, the resident cells of the cartilage, can enter into senescence in response to several stresses, leading to production of a highly inflammatory environment.…”

“…Diabetes mellitus (DM), is a chronic metabolic disorder characterized by excessive levels of blood glucose . Subsequent hyperglycemia has been shown to drive premature senescence of several cell types, including hepatocytes, pancreatic β cells, and adipocytes, by initiating a domino effect in which high production of mitochondrial ROS activates the p53-dependent DNA damage response and p16 INK4A pathways . The use of senolytics in a mice model of type 2 DM has revealed beneficial effects, with a decrease of blood glucose levels …”

Targeting Cellular Senescence in Aging and Age-Related Diseases: Challenges, Considerations, and the Emerging Role of Senolytic and Senomorphic Therapies

“…The hyperglycemia and metabolic changes of diabetes can promote cell senescence, which in turn leads to multiple diabetic complications [23]. Drugs that remove SnCs improve blood glucose levels and reduce diabetic complications [24]. In addition, diabetes leads to cardiac stem cell senescence, and Marino et al found that cardiac function could be improved in diabetic mice by eliminating SnCs in a mouse model of type 2 diabetes, which is accompanied by cardiomyopathic remodeling and cardiac dysfunction [25].…”