Table 2.
Applications of pharmacological treatment for cellular rejuvenation
| Drugs | Pharmacological characteristics | Cellular or tissue target | Rejuvenation on function (examples) | Ref. |
|---|---|---|---|---|
| Procyanidin C1 | Flavonoid | SCs | PCC1 appears to inhibit SASP formation at low concentrations and selectively kills senescent cells at higher concentrations, possibly by promoting production of ROS and mitochondrial dysfunction. Intermittent administration of PCC1 to either irradiated, senescent cell-implanted or naturally aged old mice alleviates physical dysfunction and prolongs survival. | 511 |
| BPTES | GLS1 inhibitor | SCs | Selective removal of senescent cells via glutaminolysis inhibition and improving age-related tissue dysfunction. Moreover, GLS1 inhibitors can alleviate symptoms of obese diabetes, arteriosclerosis, and nonalcoholic steatohepatitis (NASH) in elderly mice. | 512 |
| P5091 | USP7 inhibitor | SCs | The promotion of the human homolog of MDM2 ubiquitination and degradation by the ubiquitin-proteasome system, further increasing p53 levels and inhibiting the interaction of BCL-XL and BAK to selectively induce apoptosis in SCs. | 513 |
| Gallic acid | ROS inhibitor | Premature ageing | Gallic acid is a geroprotective compound that has beneficial effects against WS hMSC aging, in which the mechanism containing enhanced antioxidant response, elevated DNA repair ability, improved cell cycle kinetics and inhibited NF-κB pro-inflammatory pathway. | 514 |
| Rapamycin | mTOR inhibitor | Hematopoietic ageing | Rapamycin promotes ex vivo expansion and long-term hematopoietic reconstitution of HSCs. The increase in long-term hematopoiesis of expanded HSCs is likely attributable in part to rapamycin-mediated inhibition of HSCs senescence by the upregulation of Bmi1 and downregulation of p16. | 499 |
| Metformin | AMPK agonist | Brain ageing | Fasting or treatment with metformin can reverse the impaired metabolic function and increased DNA damage and restore the regenerative capacity of aged OPCs, improving remyelination in aged animals following focal demyelination. | 309 |
| Urolithin A | Natural postbiotic compound | Cartilage ageing | Urolithin A improves mitophagy and mitochondrial respiration in primary chondrocytes, and reduces disease progression in a mouse model of OA, as well as decreasing cartilage degeneration, synovial inflammation and pain. | 515 |
| UK-5099 | Hair follicles | Hair follicles ageing | The promotion of lactate production via blocking the entry of pyruvate into mitochondria to activate HFSCs and induce the hair cycle. | 516 |
| Melatonin | Indole heterocyclic compounds | Ovarian ageing | Melatonin delays ovarian aging by multiple mechanisms including antioxidant action, maintaining telomeres, stimulating SIRT expression and ribosome function, and by reducing autophagy. | 517 |
| Resveratrol | Polyphenol antioxidant | Cardiac ageing | Resveratrol can exert an adaptive stress response and induce autophagy, forcing the expression of cardioprotective genes and proteins such as heat shock and antioxidant proteins, | 518 |
| Nicotinamide | NAD (+) ADP-ribosyltransferase inhibitor | Vascular ageing | NMN supplementation increase SIRT1 activity, improves endothelial function and reverses age-related vascular dysfunction by decreasing oxidative stress. | 519 |
| Y27632 | Rock inhibitor | Skin ageing | Y27632 increases COL17A1 expression and regulates epidermal stem cell competition, resulting in the orchestration of skin homeostasis and reversal of skin ageing. | 450 |
| SGI-1072 | DNMT inhibitor | Renal ageing | SGI-1072 contributes significantly to epigenetic renal aging via derepressing NRF2/Klotho pathway. | 520 |
| BGE-175 | PTGDR antagonists | Immune ageing | BGE-175 inhibits the crosstalk between PGD2 and its receptor and rejuvenate immune system in the old, which shows increased migration of dendritic cells from the lungs to the lymph nodes, decreased neutrophil levels in lung tissue, and greatly improved overall survival of COVID models. | 521 |
| Ginsenoside Rb1 | Ingredients of Panax ginseng | Intestinal ageing | GRb1 could improve the intestinal aging via regulating the expression of Sirtuins family and modulating the gut microbiota in the old models. | 522 |
| Ginsenoside Rd | Ingredients of Panax ginseng | Skeletal muscle ageing | GRd ameliorates aging- and cancer-induced muscle wasting via the inhibition of STAT3 nuclear translocation, scavenging ROS and improving mitochondrial integrity. | 523 |
PCC1 procyanidin C1, SCs senescent cells, GLS1 glutaminase 1, USP7 ubiquitin-specific peptidase 7, NASH nonalcoholic steatohepatitis, MDM2 mouse double minute 2, MPC mitochondrial pyruvate carrier, DNMT DNA methyltransferase, HSCs hematopoietic stem cells, HFSCs Hair follicle stem cells, OPCs oligodendrocyte progenitor cells, PGD2 prostaglandin D2, OA osteoarthritis