Cell Cycle Status Influences Senescent Cell Responses to Senolytic Treatment | Aging-US

Aging-US #published this #research paper on August 7, 2025, in Volume 17, Issue 8, entitled “Senescent cell heterogeneity and responses to senolytic treatment are related to cell cycle status during senescence induction" by #researchers from the Buck Institute for Research on Aging, Novato, CA; USC Leonard Davis School of Gerontology, Los Angeles, CA; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD; California Pacific Medical Center Research Institute, San Francisco, CA; Johns Hopkins Physical Sciences–Oncology Center and Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD. @HopkinsEngineer @buckinstituteforresearchon4229 #aging #cellularsenescence #senolytics #cellcycle #paperspotlight #openaccess #openscience #peerreviewed #journal #publication #publishing #meded DOI - https://doi.org/10.18632/aging.206299 Corresponding authors - Denis Wirtz — wirtz@jhu.edu, Pei-Hsun Wu — pwu@jhu.edu, and Birgit Schilling — bschilling@buckinstitute.org Abstract Cellular senescence has been strongly linked to aging and age-related diseases. It is well established that the phenotype of senescent cells is highly heterogeneous and influenced by their cell type and senescence-inducing stimulus. Recent single-cell RNA-sequencing studies identified heterogeneity within senescent cell populations. However, proof of functional differences between such subpopulations is lacking. To identify functionally distinct senescent cell subpopulations, we employed high-content image analysis to measure senescence marker expression in primary human endothelial cells and fibroblasts. We found that G2-arrested senescent cells feature higher senescence marker expression than G1-arrested senescent cells. To investigate functional differences, we compared IL-6 secretion and response to ABT263 senolytic treatment in G1 and G2 senescent cells. We determined that G2-arrested senescent cells secrete more IL-6 and are more sensitive to ABT263 than G1-arrested cells. We hypothesize that cell cycle dependent DNA content is a key contributor to the heterogeneity within senescent cell populations. This study demonstrates the existence of functionally distinct senescent subpopulations even in culture. This data provides the first evidence of selective cell response to senolytic treatment among senescent cell subpopulations. Overall, this study emphasizes the importance of considering the senescent cell heterogeneity in the development of future senolytic therapies. Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206299 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, cellular senescence, imaging, heterogeneity, senolytics, cell cycle To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM