SIRT2 counteracts primate cardiac aging via deacetylation of STAT3 that silences CDKN2B

被引：32

作者：

Ye, Yanxia ^{[1
,2
,3
]}

Yang, Kuan ^{[4
,5
,6
]}

Liu, Haisong ^{[7
]}

Yu, Yang ^{[8
,9
,10
]}

Song, Moshi ^{[2
,3
,4
,11
]}

Huang, Daoyuan ^{[12
,13
,14
]}

Lei, Jinghui ^{[12
,13
,14
]}

Zhang, Yiyuan ^{[2
,3
,11
]}

Liu, Zunpeng ^{[1
,3
,5
]}

Chu, Qun ^{[1
,2
,3
,15
]}

Fan, Yanling ^{[4
]}

Zhang, Sheng ^{[5
,11
,16
]}

Jing, Yaobin ^{[2
,3
,5
,11
]}

Esteban, Concepcion Rodriguez ^{[17
]}

Wang, Si ^{[12
,13
,14
,15
]}

Belmonte, Juan Carlos Izpisua ^{[17
]}

Qu, Jing ^{[1
,2
,3
,5
]}

Zhang, Weiqi ^{[3
,4
,5
,6
]}

Liu, Guang-Hui ^{[2
,3
,5
,11
,12
,13
,14
]}

机构：

[1] Chinese Acad Sci, Inst Zool, State Key Lab Stem Cell & Reprod Biol, Beijing, Peoples R China

[2] Chinese Acad Sci, Inst Stem Cell & Regenerat, Beijing, Peoples R China

[3] Beijing Inst Stem Cell & Regenerat Med, Beijing, Peoples R China

[4] Chinese Acad Sci, Beijing Inst Genom, CAS Key Lab Genom & Precis Med, Beijing, Peoples R China

[5] Univ Chinese Acad Sci, Beijing, Peoples R China

[6] Univ Chinese Acad Sci, Sinodanish Coll, Beijing, Peoples R China

[7] Hunan Univ, Sch Biomed Sci, Changsha, Peoples R China

[8] Peking Univ Third Hosp, Dept Obstet & Gynecol, Ctr Reprod Med, Beijing Key Lab Reprod Endocrinol & Assisted Repr, Beijing, Peoples R China

[9] Peking Univ Third Hosp, Dept Obstet & Gynecol, Ctr Reprod Med, Key Lab Assisted Reprod,Minist Educ, Beijing, Peoples R China

[10] Peking Univ Third Hosp, Clin Stem Cell Res Ctr, Beijing, Peoples R China

[11] Chinese Acad Sci, Inst Zool, State Key Lab Membrane Biol, Beijing, Peoples R China

[12] Capital Med Univ, Xuanwu Hosp, Adv Innovat Ctr Human Brain Protect, Beijing, Peoples R China

[13] Capital Med Univ, Xuanwu Hosp, Natl Clin Res Ctr Geriatr Disorders, Beijing, Peoples R China

[14] Capital Med Univ, Xuanwu Hosp, Int Ctr Aging & Canc, Aging Translat Med Ctr, Beijing, Peoples R China

[15] Fifth Peoples Hosp Chongqing, Chongqing, Peoples R China

[16] Chinese Acad Sci, CAS Ctr Excellence Brain Sci & Intelligence Techn, Inst Brain Intelligence Technol Shanghai, State Key Lab Brain & Cognit Sci,Inst Biophys, Beijing, Peoples R China

[17] Altos Labs Inc, San Diego, CA USA

来源：

NATURE AGING | 2023年 / 3卷 / 10期

基金：

中国博士后科学基金; 中国国家自然科学基金; 北京市自然科学基金;

关键词：

CARDIOVASCULAR-DISEASE ENTERPRISES; TUMOR-SUPPRESSOR; MAJOR SHAREHOLDERS; HEART; CARDIOMYOCYTES; HETEROCHROMATIN; ACETYLATION; SENESCENCE; SIRTUINS; ARTERIAL;

D O I：

10.1038/s43587-023-00486-y

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Aging is a major risk factor contributing to pathophysiological changes in the heart, yet its intrinsic mechanisms have been largely unexplored in primates. In this study, we investigated the hypertrophic and senescence phenotypes in the hearts of aged cynomolgus monkeys as well as the transcriptomic and proteomic landscapes of young and aged primate hearts. SIRT2 was identified as a key protein decreased in aged monkey hearts, and engineered SIRT2 deficiency in human pluripotent stem cell-derived cardiomyocytes recapitulated key senescence features of primate heart aging. Further investigations revealed that loss of SIRT2 in human cardiomyocytes led to the hyperacetylation of STAT3, which transcriptionally activated CDKN2B and, in turn, triggered cardiomyocyte degeneration. Intra-myocardial injection of lentiviruses expressing SIRT2 ameliorated age-related cardiac dysfunction in mice. Taken together, our study provides valuable resources for decoding primate cardiac aging and identifies the SIRT2-STAT3-CDKN2B regulatory axis as a potential therapeutic target against human cardiac aging and aging-related cardiovascular diseases.

引用

页码：1269 / +

页数：30

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