TABLE 1.
The interventional effects of senotherapy in metabolic diseases.
| Types/Complications | Agent | Main effects | Cellular senescence-related signalling pathways | Targeting senescent cell types | |
|---|---|---|---|---|---|
| Diabetes | T2DM | Quercetin | Reduces blood glucose concentration and regulates key signalling pathways to reduce ROS damage Dhanya (2022) | Bcl-2 family, p53/p21/serpine, and PI3K/AKT | Pancreatic β-cells |
| T1DM | Navitoclax (ABT-263) | Selectively binds to Bcl-2, Bcl-XL, and Bcl-w, eliminates senescent beta cells with high expression of Bcl-2, and reduces the level of islet inflammationThompson et al. (2019); Sreekumar et al. (2020) | Bcl-2 family (Bcl-2, Bcl-xL, Bcl-w) | Pancreatic β-cell HUVECs | |
| DKD | D + Q | Downregulation of senescence-associated cells, reduction of SASP factors in the blood, and reduction of senescent cell load in adipose tissue Hickson et al. (2019) | Dependent receptor/Src kinase/tyrosine kinase, Bcl-2 family, p53/p21 | Adipocytes and adipose progenitor cells | |
| PDR | UBX-1325 | enhanced the effects of anti-VEGF drugs, downregulated SASP and general aging, and also improved the OIR and STZ-induced retinal vasculature Crespo-Garcia et al. (2021); Hassan and Bhatwadekar (2022) | BCL-xL inhibitor | HUVECs, monocytes, retinal cells | |
| PDR | UBX1967 | activation of cystein-3 and other intrinsic pathways that trigger apoptosis. Improved the retinal vascular system, allowing the reorganization of vascular units Crespo-Garcia et al. (2021); Hassan and Bhatwadekar (2022) | BCL-xL inhibitor | HUVECs, retinal cells | |
| Atherosclerosis | \ | Navitoclax (ABT-263) | ABT-263 eliminated dysfunctional senescent cells from atherosclerotic plaques to delay atherosclerosis, respectively Sreekumar et al. (2020) | Bcl-2 family (Bcl-2, Bcl-Xl, Bcl-w) | HUVECs |
| \ | D + Q | It reduces the number of senescent cells in the middle aorta and improves vasodilatory function Roos et al. (2016) | Dependent receptor/Src kinase/tyrosinase, Bcl-2 family, p53/p21/PI3K/AKT, etc | Aortic cells | |
| Osteoporosis | \ | D + Q | Elimination of senescent cells with higher bone volume and strength and better bone microarchitecture Farr et al. (2017) | Dependent receptor/Src kinase/tyrosine kinase, Bcl-2 family, p53/p21, etc | Osteoclast |
| \ | Jak Inhibitors | Inhibit the pro-inflammatory secretion group of senescent cells, significantly improve the microenvironment of mouse bone cells, and increase the bone volume and strength of mouse bones Farr et al. (2017) | Selective inhibition of JAK kinase, blocking JAK/STAT signaling pathway | Osteoblast/osteoclast\CFU-M | |
| \ | Lacrimalin (Flavonoid) | Lacquer inhibits osteoclast differentiation by suppressing the NFATc1 signaling pathway while stimulating osteoblast differentiation by increasing RUNX2 expression Molagoda et al. (2021) | PI3K/AKT | Osteoblasts/osteoclasts |
DKD, diabetic nephropathy; PDR, diabetic retinopathy; AMD, age-related macular degeneration; D, dasatinib; Q, Quercetin.