AUTHOR=Hudgins Adam D. , Tazearslan Cagdas , Tare Archana , Zhu Yizhou , Huffman Derek , Suh Yousin 

TITLE=Age- and Tissue-Specific Expression of Senescence Biomarkers in Mice

JOURNAL=Frontiers in Genetics

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2018.00059

DOI=10.3389/fgene.2018.00059

ISSN=1664-8021

ABSTRACT=<p>Cellular senescence is a state of irreversible cellular growth arrest accompanied by distinct changes in gene expression and the acquisition of a complex proinflammatory secretory profile termed the senescence-associated secretory phenotype (SASP). Senescent cells accumulate in aged tissues and contribute to age-related disease in mice. Increasing evidence that selective removal of senescent cells can ameliorate diseases of late life and extend lifespan in mice has given rise to the development of senolytics that target senescent cells as anti-aging therapeutics. To realize the full potential of senolytic medicine, robust biomarkers of senescence must be in place to monitor the <italic>in vivo</italic> appearance of senescent cells with age, as well as their removal by senolytic treatments. Here we investigate the dynamic changes in expression of the molecular hallmarks of senescence, including <italic>p16<sup>Ink4a</sup></italic>, <italic>p21<sup>Cip1</sup></italic>, and SASP factors in multiple tissues in mice during aging. We show that expression of these markers is highly variable in age- and tissue-specific manners. Nevertheless, <italic>Mmp12</italic> represents a robust SASP factor that shows consistent age-dependent increases in expression across all tissues analyzed in this study and <italic>p16<sup>Ink4a</sup></italic> expression is consistently increased with age in most tissues. Likewise, in humans <italic>CDKN2A</italic> (<italic>p16<sup>Ink4a</sup></italic>) is one of the top genes exhibiting elevated expression in multiple tissues with age as revealed by data analysis of the Genotype-Tissue Expression (GTEx) project. These results support the targeting of <italic>p16<sup>Ink4a</sup></italic> expressing-cells in senolytic treatments, while emphasizing the need to establish a panel of robust biomarkers of senescence <italic>in vivo</italic> in both mice and humans.</p>