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. 2018 Feb 23:9:59.
doi: 10.3389/fgene.2018.00059. eCollection 2018.

Age- and Tissue-Specific Expression of Senescence Biomarkers in Mice (V体育ios版)

Adam D Hudgins  1 , Cagdas Tazearslan  1 , Archana Tare  1 , Yizhou Zhu  1 , Derek Huffman  2   3 , Yousin Suh  1   3   4
Affiliations

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

Adam D Hudgins et al. Front Genet. .

Abstract

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 in vivo 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 p16Ink4a , p21Cip1 , 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, Mmp12 represents a robust SASP factor that shows consistent age-dependent increases in expression across all tissues analyzed in this study and p16Ink4a expression is consistently increased with age in most tissues. Likewise, in humans CDKN2A (p16Ink4a ) 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 VSports手机版. These results support the targeting of p16Ink4a expressing-cells in senolytic treatments, while emphasizing the need to establish a panel of robust biomarkers of senescence in vivo in both mice and humans. .

Keywords: SASP; aging; biomarkers; cellular senescence; gene expression V体育安卓版. .

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Figures (VSports注册入口)

FIGURE 1
FIGURE 1
Senescence marker/SASP factor gene expression exhibits age- and tissue-specific patterns. Expression of a panel of SASP factors, and the cyclin-dependent kinase inhibitors p16Ink4a and p21Cip1, as determined by RT-qPCR, in hypothalamus (A), heart (B), liver (C), and kidney (D) (n = 4 females per group). Fold change in expression of all genes is relative to 4-month-old tissue. ∗P < 0.05; ∗∗P < 0.01; ∗∗∗P < 0.001 (unpaired two-tailed Welch’s t-test with Dunnett’s multiple comparison). N.D. = Not detectable.
FIGURE 2
FIGURE 2
p16Ink4a expression is significantly elevated with age in multiple tissues in humans. Expression heatmap of the top 20 human genes showing increased expression with age across 9 tissues (subcutaneous adipose, tibial artery, left ventricle heart, lung, skeletal muscle, tibial nerve, skin from sun exposed lower leg, thyroid, and whole blood) analyzed by RNA-seq of the GTEx consortium. CDKN2A (p16Ink4a) exhibits significant increases in expression in 6 tissues with age. Genes are ranked from top to bottom according to number of tissues that show significant age-dependent upregulation. ∗P < 0.05; ∗∗P < 0.01; ∗∗∗P < 0.001 (FDR adjusted p-values). Beta represents the linear regression coefficient used to determine age-dependent expression change, with higher values indicating higher expression with age.
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V体育平台登录 - References

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