Paper Spotlight: Insufficient Markers of Senescent Cells

9 views

|

March 16, 2022

Aging (Aging-US) published this research paper in Volume 9, Issue 8, entitled, "p16(Ink4a) and senescence-associated β-galactosidase can be induced in macrophages as part of a reversible response to physiological stimuli" by researchers from Everon Biosciences, Inc., Buffalo, NY; Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY; Department of Tumor Immunology, Roswell Park Cancer Institute, Buffalo, NY. DOI - https://doi.org/10.18632/aging.101268 Corresponding authors - Olga Chernova - ochernova@tartiscorp.com, and Andrei Gudkov - andrei.gudkov@roswellpark.org Abstract Constitutive p16Ink4a expression, along with senescence-associated β-galactosidase (SAβG), are commonly accepted biomarkers of senescent cells (SCs). Recent reports attributed improvement of the healthspan of aged mice following p16Ink4a-positive cell killing to the eradication of accumulated SCs. However, detection of p16Ink4a/SAβG-positive macrophages in the adipose tissue of old mice and in the peritoneal cavity of young animals following injection of alginate-encapsulated SCs has raised concerns about the exclusivity of these markers for SCs. Here we report that expression of p16Ink4a and SAβG in macrophages is acquired as part of a physiological response to immune stimuli rather than through senescence, consistent with reports that p16Ink4a plays a role in macrophage polarization and response. Unlike SCs, p16Ink4a/SAβG-positive macrophages can be induced in p53-null mice. Macrophages, but not mesenchymal SCs, lose both markers in response to M1- [LPS, IFN-α, Poly(I:C)] and increase their expression in response to M2-inducing stimuli (IL-4, IL-13). Moreover, interferon-inducing agent Poly(I:C) dramatically reduced p16Ink4a expression in vivo in our alginate bead model and in the adipose tissue of aged mice. These observations suggest that the antiaging effects following eradication of p16Ink4a-positive cells may not be solely attributed to SCs but also to non-senescent p16Ink4a/SAβG-positive macrophages. Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.101268 Author interview - https://www.youtube.com/watch?v=fJXK4rs1iwo Keywords - aging, macrophage, senescent cell, p16(Ink4a), beta-galactosidase About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at http://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/agingus​ LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Aging-US is published by Impact Journals, LLC: http://www.ImpactJournals.com​​ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

Cancer ResearchCell ScienceDrug Discovery

Keep up to date with all your favourite videos and channels.

Get personalised notifications on new releases and channel content by subscribing to the LabTube eNewsletter.