Language

English

Publication Date

1-1-2026

Journal

Aging Cell

DOI

10.1111/acel.70358

PMID

41462575

PMCID

PMC12748526

PubMedCentral® Posted Date

12-29-2022

PubMedCentral® Full Text Version

Post-print

Abstract

The senescent cell (SC) fate is linked to aging, multiple disorders and diseases, and physical dysfunction. Senolytics, agents that selectively eliminate 30%-70% of SCs, act by transiently disabling the senescent cell antiapoptotic pathways (SCAPs), which defend those SCs that are proapoptotic and pro-inflammatory from their own senescence-associated secretory phenotype (SASP). Consistent with this, a JAK/STAT inhibitor, Ruxolitinib, which attenuates the pro-inflammatory SASP of senescent human preadipocytes, caused them to become "senolytic-resistant". Administering senolytics to obese mice selectively decreased the abundance of the subset of SCs that is pro-inflammatory. In cell cultures, the 30%-70% of human senescent preadipocytes or human umbilical vein endothelial cells (HUVECs) that are senolytic-resistant (to Dasatinib or Quercetin, respectively) had increased p16

Keywords

Humans, Animals, Senotherapeutics, Senescence-Associated Secretory Phenotype, Mice, Cellular Senescence, Pyrimidines, Nitriles, Pyrazoles, Dasatinib, Human Umbilical Vein Endothelial Cells, cellular senescence, senescent cell subtypes, senolytics, senosensitizers

Published Open-Access

yes

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