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, 42 (12), 821-827

Senolytics and Senostatics: A Two-Pronged Approach to Target Cellular Senescence for Delaying Aging and Age-Related Diseases


Senolytics and Senostatics: A Two-Pronged Approach to Target Cellular Senescence for Delaying Aging and Age-Related Diseases

Chanhee Kang. Mol Cells.


Aging is the most important single risk factor for many chronic diseases such as cancer, metabolic syndrome, and neurodegenerative disorders. Targeting aging itself might, therefore, be a better strategy than targeting each chronic disease individually for enhancing human health. Although much should be achieved for completely understanding the biological basis of aging, cellular senescence is now believed to mainly contribute to organismal aging via two independent, yet not mutually exclusive mechanisms: on the one hand, senescence of stem cells leads to exhaustion of stem cells and thus decreases tissue regeneration. On the other hand, senescent cells secrete many proinflammatory cytokines, chemokines, growth factors, and proteases, collectively termed as the senescence-associated secretory phenotype (SASP), which causes chronic inflammation and tissue dysfunction. Much effort has been recently made to therapeutically target detrimental effects of cellular senescence including selectively eliminating senescent cells (senolytics) and modulating a proinflammatory senescent secretome (senostatics). Here, we discuss current progress and limitations in understanding molecular mechanisms of senolytics and senostatics and therapeutic strategies for applying them. Furthermore, we propose how these novel interventions for aging treatment could be improved, based on lessons learned from cancer treatment.

Keywords: age-associated inflammation; aging; cellular senescence; senescence-associated secretory phenotype; senolytics; senostatics.

Conflict of interest statement


The author has no potential conflicts of interest to disclose.


Fig. 1
Fig. 1. Current status of senolytics and senostatics
(A) Pathways targeted by currently available senolytic and senostatic drugs. (B) Human diseases have been shown to be delayed by senotherapy (modified from EFNB1, ephrin B1; GF, growth factor; PI3K, phosphoinositide 3-kinases; MDM2, mouse double minute 2 homolog; Bcl2, B-cell lymphoma 2; Mcl-1, myeloid cell leukemia 1; Bcl-xL, B-cell lymphoma-extra large; FOXO4, forkhead Box O4; D + Q, co-treatment of dasatinib and quercetin.
Fig. 2
Fig. 2. Lessons from cancer treatment that help to improve senolytics and senostatics
Three new strategies to improve senotherapy adapted from the concepts that previously succeeded for cancer treatment: 1) non-senescence addiction (A), 2) combinatorial drug treatment (B), and 3) senescence immunotherapy (C).

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