Age- and Tissue-Specific Expression of Senescence Biomarkers in Mice.
Age- and Tissue-Specific Expression of Senescence Biomarkers in Mice.
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DOI：
10.3389/fgene.2018.00059
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发表时间：
2018
影响因子：
3.7
通讯作者：
Suh Y
中科院分区：
文献类型：
--
作者：
Hudgins AD;Tazearslan C;Tare A;Zhu Y;Huffman D;Suh Y
细胞衰老是一种不可逆的细胞生长停滞状态，伴随着基因表达的明显变化和称为衰老相关分泌表型（SASP）的复杂促炎分泌谱的获得。衰老细胞在衰老组织中积累，并导致小鼠的年龄相关疾病。越来越多的证据表明，选择性去除衰老细胞可以改善老年疾病并延长小鼠的寿命，这引起了靶向衰老细胞作为抗衰老治疗剂的衰老药物的发展。为了实现衰老药物的全部潜力，必须建立强大的衰老生物标志物，以监测衰老细胞随年龄的体内外观，以及通过衰老治疗对其的去除。在这里，我们调查衰老的分子标志，包括p16 Ink 4a，p21 Cip 1，和SASP因子在小鼠衰老过程中的多个组织中的表达的动态变化。我们发现，这些标志物的表达是高度可变的年龄和组织特异性的方式。然而，Mmp 12代表了一个稳健的SASP因子，在本研究中分析的所有组织中显示出一致的年龄依赖性表达增加，并且在大多数组织中p16 Ink 4a表达随着年龄的增加而一致增加。同样，在人类中，CDKN 2A（p16 Ink 4a）是随着年龄增长在多种组织中表现出表达升高的主要基因之一，如基因型-组织表达（GTEx）项目的数据分析所揭示的。这些结果支持在衰老清除治疗中靶向表达p16 Ink 4a的细胞，同时强调需要在小鼠和人类中建立一组体内衰老的稳健生物标志物。
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. 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.
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影响因子：
78.5
作者：
Collado, Manuel;Serrano, Manuel
通讯作者：
Serrano, Manuel
影响因子：
64.8
作者：
Baker DJ;Childs BG;Durik M;Wijers ME;Sieben CJ;Zhong J;Saltness RA;Jeganathan KB;Verzosa GC;Pezeshki A;Khazaie K;Miller JD;van Deursen JM
通讯作者：
van Deursen JM
影响因子：
3.7
作者：
Coppé JP;Patil CK;Rodier F;Krtolica A;Beauséjour CM;Parrinello S;Hodgson JG;Chin K;Desprez PY;Campisi J
通讯作者：
Campisi J
DOI：
10.1146/annurev-pathol-121808-102144
发表时间：
2010
期刊：
Annual review of pathology
影响因子：
--
作者：
Coppé JP;Desprez PY;Krtolica A;Campisi J
通讯作者：
Campisi J
DOI：
10.1093/gerona/54.11.b492
发表时间：
1999-11-01
影响因子：
5.1
作者：
Turturro, A;Witt, WW;Hart, RW
通讯作者：
Hart, RW