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Identification and Application of Gene Expression Signatures Associated with Lifespan ExtensionTyshkovskiy, Alexander1,2,3; Bozaykut, Perinur1; Borodinova, Anastasia A.4; Gerashchenko, Maxim, V1; Ables, Gene P.5; Garratt, Michael6,7; Khaitovich, Philipp2,8,9,10![](\"http://www.baidu.com/image/person.jpg\")
; Clish, Clary B.11; Miller, Richard A.6,7; Gladyshev, Vadim N.1,112019-09-03发表期刊CELL METABOLISM![](\"http://www.baidu.com/image/waiting.gif\")
ISSN1550-4131卷号30期号:3页码:573-+发表状态已发表DOI10.1016/j.cmet.2019.06.018摘要Several pharmacological, dietary, and genetic interventions that increase mammalian lifespan are known, but general principles of lifespan extension remain unclear. Here, we performed RNA sequencing (RNA-seq) analyses of mice subjected to 8 longevity interventions. We discovered a feminizing effect associated with growth hormone regulation and diminution of sex-related differences. Expanding this analysis to 17 interventions with public data, we observed that many interventions induced similar gene expression changes. We identified hepatic gene signatures associated with lifespan extension across interventions, including upregulation of oxidative phosphorylation and drug metabolism, and showed that perturbed pathways may be shared across tissues. We further applied the discovered longevity signatures to identify new lifespan-extending candidates, such as chronic hypoxia, KU-0063794, and ascorbyl-palmitate. Finally, we developed GENtervention, an app that visualizes associations between gene expression changes and longevity. Overall, this study describes general and specific transcriptomic programs of lifespan extension in mice and provides tools to discover new interventions.收录类别SCI资助项目Orentreich Foundation for the Advancement of Science, Inc.[ASL20]WOS研究方向Cell Biology; Endocrinology MetabolismWOS类目Cell Biology; Endocrinology MetabolismWOS记录号WOS:000484370400016出版者CELL PRESSWOS关键词DRUG-METABOLIZING-ENZYMES; CALORIC RESTRICTION; DIETARY RESTRICTION; NORDIHYDROGUAIARETIC ACID; SEXUAL-DIMORPHISM; OXIDATIVE STRESS; MAMMALIAN TARGET; CONNECTIVITY MAP; PROTEIN GENE; MALE-MICE原始文献类型Article被引频次：3[WOS][WOS记录][WOS相关记录]文献类型期刊论文条目标识符http://kms.shanghaitech.edu.cn/handle/2MSLDSTB/80011专题生命科学与技术学院_特聘教授组_Philipp Khaitovich组通讯作者Gladyshev, Vadim N.作者单位1.Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA2.Skolkovo Inst Sci & Technol, Moscow 121205, Russia3.Moscow MV Lomonosov State Univ, Belozersky Inst Physicochem Biol, Moscow 119234, Russia4.Russian Acad Sci, Inst Higher Nervous Act & Neurophysiol, Moscow 117485, Russia5.Orentreich Fdn Adv Sci Inc, Cold Spring on Hudson, NY USA6.Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA7.Univ Michigan, Geriatr Ctr, Ann Arbor, MI 48109 USA8.CAS MPG Partner Inst Computat Biol, Comparat Biol Grp, 320 Yue Yang Rd, Shanghai 200031, Peoples R China9.Max Planck Inst Evolutionary Anthropol, Deutsch Pl 6, D-04103 Leipzig, Germany10.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai 200031, Peoples R China11.Broad Inst, Cambridge, MA 02142 USA推荐引用方式GB/T 7714Tyshkovskiy, Alexander,Bozaykut, Perinur,Borodinova, Anastasia A.,et al. Identification and Application of Gene Expression Signatures Associated with Lifespan Extension[J]. CELL METABOLISM,2019,30(3):573-+.Tyshkovskiy, Alexander.,Bozaykut, Perinur.,Borodinova, Anastasia A..,Gerashchenko, Maxim, V.,Ables, Gene P..,...&Gladyshev, Vadim N..(2019).Identification and Application of Gene Expression Signatures Associated with Lifespan Extension.CELL METABOLISM,30(3),573-+.Tyshkovskiy, Alexander,et al.\"Identification and Application of Gene Expression Signatures Associated with Lifespan Extension\".CELL METABOLISM 30.3(2019):573-+.
