Advancements in therapeutic drugs targeting of senescence

Abstract

Aging leads to a high burden on society, both medically and economically. Cellular senescence plays an essential role in the initiation of aging and age-related diseases. Recent studies have highlighted the therapeutic value of senescent cell deletion in natural aging and many age-related disorders. However, the therapeutic strategies for manipulating cellular senescence are still at an early stage of development. Among these strategies, therapeutic drugs that target cellular senescence are arguably the most highly anticipated. Many recent studies have demonstrated that a variety of drugs exhibit healthy aging effects. In this review, we summarize different types of drugs promoting healthy aging - such as senolytics, senescence-associated secretory phenotype (SASP) inhibitors, and nutrient signaling regulators - and provide an update on their potential therapeutic merits. Taken together, our review synthesizes recent advancements in the therapeutic potentialities of drugs promoting healthy aging with regard to their clinical implications.

Keywords: advancement; drug; healthy aging; senescence; senolytics.

Figure 1.

The signaling pathways of senescence. Two main pathways, p16^INK4a/Rb and p53/p21^CIP1, regulate senescence-mediated growth arrest, and they both converge on repression of CDK4/6. In addition, ARF inhibits MDM2, resulting in increased levels of p53 and thereby allowing cross talk with the p53/p21^CIP1 pathways. ROS, reactive oxygen species.

Figure 2.

The targeted signaling pathways involved in senolytics. Senolytic drugs, such as Dasatinib, Quercetin, Fisetin, 17-DMAG, Navitoclax, Catechins, etc., induce the senescent cells apoptosis through different pathways, including the BCL-2/BCL-xL, P53, and PI3K/AKT pathways.

Figure 3.

Targeted signaling pathways involved in SASP inhibitor. These drugs include antioxidants, Wnts/β-catenin signaling inhibitor, JAK inhibitor, and so on. The related pathways include Nrf2, NF-κB, Wnt/β-catenin, and JAK pathways. JAK, Janus kinase; ROS, reative oxygen species; SASP, senescence-associated secretory phenotype.

Figure 4.

The targeted signaling pathways involved in nutrient signaling regulator. These drugs include resveratrol, curcumin, metformin, rapamycin, Lycium barbarum, etc. The related signaling pathways include the Sirtuin, mTOR, and AMPK pathways.