concept

senolytics

Also known as: senolytic drugs, senolytic agents

Facts (23)

Sources

Cellular rejuvenation: molecular mechanisms and potential ... - Nature nature.com Nature Mar 14, 2023 20 facts

claimSenolytics, which remove senescent cells, and senomorphics, which attenuate the senescence-associated secretory phenotype (SASP), can ameliorate diabetes and its complications by alleviating insulin resistance and reducing tissue inflammation.

procedureA sequential therapy regimen for cancer involves inducing therapy-induced senescence (TIS) followed by the administration of a senolytic agent to kill the senescent cancer cells.

claimSenolytic agents and senomorphic therapy are potential treatments for osteoarthritis (OA).

measurementA clinical trial (NCT02848131) suggested that senolytics using a combination of Dasatinib and Quercetin (D + Q) improved physical function in patients with chronic kidney disease (CKD).

claimStrategies for tissue regeneration include the elimination of senescent cells with senolytics, exogenous stem cell transplantation to replenish the stem cell pool, the use of extracellular vesicles (EVs) and their engineered derivatives to alleviate cellular senescence, and the application of wound inflammatory and chemical compounds to rejuvenate stem cells.

claimSenolytics and senomorphics are potential skin rejuvenation drugs because they possess anti-inflammatory and melanogenic properties that protect skin, prevent carcinogenesis, delay aging, and reduce age-related diseases.

claimDasatinib (D), quercetin (Q), and fisetin (F) were chosen for senolytic study because they have established safety profiles or FDA approval for other human purposes, facilitating a faster transition from research to clinical application.

claimSASP inhibitors require continuous treatment to maintain suppression of the Senescence-Associated Secretory Phenotype (SASP), which increases the likelihood of side effects compared to the intermittent administration of senolytic drugs.

claimThe immune system, specifically NK cells, macrophages, and cytotoxic T cells, performs immunosurveillance and is responsible for the final removal of apoptotic senescent cells induced by senolytic strategies.

referenceDookun, E., Passos, J. F., Arthur, H. M., and Richardson, G. D. reviewed the therapeutic potential of senolytics in cardiovascular disease.

claimSenolytics, which kill senescent cells and stop the bystander effects of the senescence-associated secretory phenotype (SASP), are a potential treatment for age-related macular degeneration (AMD) due to the role of cellular senescence in its pathogenesis.

claimCellular senescence can cause inflammation and metabolic disturbances associated with obesity, and the elimination of senescent cells with senolytic interventions may help improve obesity clinically.

measurementBioinformatic analysis has identified forty-six compounds that target Senescent Cell Anti-Apoptotic Pathways (SCAP) and may function as senolytics.

referenceSenolytics improve physical function and increase lifespan in old age, according to Chang et al. in Nature Medicine (2018).

referenceArora et al. (2021) discussed the potential of senolytics for alleviating diabetes and its complications.

claimClearance of senescent cells (SCs) and decreasing the senescence-associated secretory phenotype (SASP) benefit organ repair and disease treatment, but senolytics often have poor cell selectivity that may damage normal tissue, and SASP inhibitors targeting specific secretory factors have limited therapeutic effects on multiple factors-mediated diseases.

referenceSenolytics are a potential therapeutic approach for kidney repair.

referenceThe transcriptome of senescent cells can be used to identify senolytic drugs, as described by Yosef et al. in Aging Cell (2015).

claimSenolytic drugs exhibit cell or tissue-specific sensitivity due to the varying contributions of nodes across the Senescent Cell Anti-Apoptotic Pathways (SCAP) network in different senescent cell subpopulations.

referenceSenolytics can eliminate senescent cells and alleviate intervertebral disc degeneration.

Cellular senescence: from homeostasis to pathological implications ... frontiersin.org Frontiers 3 facts

referenceSenolytics and senomorphics are natural and synthetic therapeutics used in the treatment of aging and chronic diseases, as reviewed by Lagoumtzi and Chondrogianni in Free Radical Biology and Medicine (2021).

referenceThe review article 'Targeting cell senescence and senolytics: novel interventions for age-related endocrine dysfunction' was published in Endocrine Reviews in 2024 (Volume 45, pages 655–75).

referenceCellular senescence and senolytics are being developed as clinical interventions, as outlined by Chaib et al. in Nature Medicine (2022).