Novel Marker of Aging and Cellular Senescence: Cdkn1a Transcript Variant 2
Channel: Aging (Aging-US)
Date: 30/07/2021

Aging published this trending priority research paper on May 25, 2021, entitled, “Cdkn1a transcript variant 2 is a marker of aging and cellular senescence” by researchers from Buck Institute for Research on Aging, Novato, CA; Universidad de Córdoba, Campus de Excelencia Internacional Agroalimentario, 14071, Córdoba, Spain; Universidad Mayor, Santiago 2422, Chile; Geroscience Center for Brain Health and Metabolism, Santiago, Chile; Unity Biotechnology Inc., South San Francisco, CA; University of California, Santa Barbara, CA ; University of California, Berkeley, CA; Barcelona Institute of Science and Technology, Barcelona 08028, Spain.

Abstract:
Cellular senescence is a cell fate response characterized by a permanent cell cycle arrest driven primarily the by cell cycle inhibitor and tumor suppressor proteins p16Ink4a and p21Cip1/Waf1. In mice, the p21Cip1/Waf1 encoding locus, Cdkn1a, is known to generate two transcripts that produce identical proteins, but one of these transcript variants is poorly characterized. We show that the Cdkn1a transcript variant 2, but not the better-studied variant 1, is selectively elevated during natural aging across multiple mouse tissues. Importantly, mouse cells induced to senescence in culture by genotoxic stress (ionizing radiation or doxorubicin) upregulated both transcripts, but with different temporal dynamics: variant 1 responded nearly immediately to genotoxic stress, whereas variant 2 increased much more slowly as cells acquired senescent characteristics. Upon treating mice systemically with doxorubicin, which induces widespread cellular senescence in vivo, variant 2 increased to a larger extent than variant 1. Variant 2 levels were also more sensitive to the senolytic drug ABT-263 in naturally aged mice. Thus, variant 2 is a novel and more sensitive marker than variant 1 or total p21Cip1/Waf1 protein for assessing the senescent cell burden and clearance in mice.

Press release - https://www.aging-us.com/news_room/cdkn1a-transcript-variant-2-is-a-marker-of-aging-and-cellular-senescence

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DOI - https://doi.org/10.18632/aging.203110
Full text - https://www.aging-us.com/article/203110/text

Correspondence to: Judith Campisi email: jcampisi@buckinstitute.org

Keywords: p21, p53, mouse dermal fibroblast, ionizing radiation, doxorubicin

About Aging

Launched in 2009, Aging 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 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.

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