The Role of Telomeres in Human Disease.
The Role of Telomeres in Human Disease.
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DOI：
10.1146/annurev-genom-010422-091101
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发表时间：
2022-08-31
影响因子：
8.7
通讯作者：
中科院分区：
文献类型：
--
作者：
端粒生物学首先在玉米、纤毛虫、酵母和小鼠中进行了研究，近几十年来，它为理解常见疾病机制提供了信息，对患者护理具有广泛意义。短端粒综合征是最普遍的早衰症，具有影响肺和造血系统的突出表型。人们对一组新发现的癌症易感综合征知之甚少，这些综合征与延长端粒的突变有关。来自孟德尔遗传学和流行病学的大量新数据现在提供了一个机会来重新考虑与端粒在人类衰老和癌症中的作用相关的范式，并且在某些情况下，研究结果与模型系统的解释存在分歧。例如，短端粒被认为是基因组不稳定性的有力驱动因素，但年龄相关的实体瘤在短端粒综合征患者中很少见，T细胞免疫缺陷解释了它们的光谱。更常见的是，短端粒促进克隆造血，包括体细胞逆转，提供了一种新的白血病发生模式，是独立的基因组不稳定性。另一方面，在体外延长细胞寿命的长端粒现在被认为是人口研究中最常见的癌症生殖系风险因素。通过这个当代的透镜，我在这里重新审视端粒在人类衰老中的作用，重点是短端粒和长端粒如何通过不同的机制驱动癌症演变。
Telomere biology was first studied in maize, ciliates, yeast, and mice, and in recent decades, it has informed understanding of common disease mechanisms with broad implications for patient care. Short telomere syndromes are the most prevalent premature aging disorders, with prominent phenotypes affecting the lung and hematopoietic system. Less understood are a newly recognized group of cancer-prone syndromes that are associated with mutations that lengthen telomeres. A large body of new data from Mendelian genetics and epidemiology now provides an opportunity to reconsider paradigms related to the role of telomeres in human aging and cancer, and in some cases, the findings diverge from what was interpreted from model systems. For example, short telomeres have been considered potent drivers of genome instability, but age-associated solid tumors are rare in individuals with short telomere syndromes, and T cell immunodeficiency explains their spectrum. More commonly, short telomeres promote clonal hematopoiesis, including somatic reversion, providing a new leukemogenesis paradigm that is independent of genome instability. Long telomeres, on the other hand, which extend the cellular life span in vitro, are now appreciated to be the most common shared germline risk factor for cancer in population studies. Through this contemporary lens, I revisit here the role of telomeres in human aging, focusing on how short and long telomeres drive cancer evolution but through distinct mechanisms.
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影响因子：
10.3
作者：
Aoude, Lauren G.;Pritchard, Antonia L.;Hayward, Nicholas K.
通讯作者：
Hayward, Nicholas K.
影响因子：
4.5
作者：
Aubert G;Baerlocher GM;Vulto I;Poon SS;Lansdorp PM
通讯作者：
Lansdorp PM
DOI：
10.1038/nrg3246
发表时间：
2012-10
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
64.8
作者：
Bick AG;Weinstock JS;Nandakumar SK;Fulco CP;Bao EL;Zekavat SM;Szeto MD;Liao X;Leventhal MJ;Nasser J;Chang K;Laurie C;Burugula BB;Gibson CJ;Lin AE;Taub MA;Aguet F;Ardlie K;Mitchell BD;Barnes KC;Moscati A;Fornage M;Redline S;Psaty BM;Silverman EK;Weiss ST;Palmer ND;Vasan RS;Burchard EG;Kardia SLR;He J;Kaplan RC;Smith NL;Arnett DK;Schwartz DA;Correa A;de Andrade M;Guo X;Konkle BA;Custer B;Peralta JM;Gui H;Meyers DA;McGarvey ST;Chen IY;Shoemaker MB;Peyser PA;Broome JG;Gogarten SM;Wang FF;Wong Q;Montasser ME;Daya M;Kenny EE;North KE;Launer LJ;Cade BE;Bis JC;Cho MH;Lasky-Su J;Bowden DW;Cupples LA;Mak ACY;Becker LC;Smith JA;Kelly TN;Aslibekyan S;Heckbert SR;Tiwari HK;Yang IV;Heit JA;Lubitz SA;Johnsen JM;Curran JE;Wenzel SE;Weeks DE;Rao DC;Darbar D;Moon JY;Tracy RP;Buth EJ;Rafaels N;Loos RJF;Durda P;Liu Y;Hou L;Lee J;Kachroo P;Freedman BI;Levy D;Bielak LF;Hixson JE;Floyd JS;Whitsel EA;Ellinor PT;Irvin MR;Fingerlin TE;Raffield LM;Armasu SM;Wheeler MM;Sabino EC;Blangero J;Williams LK;Levy BD;Sheu WH;Roden DM;Boerwinkle E;Manson JE;Mathias RA;Desai P;Taylor KD;Johnson AD;NHLBI Trans-Omics for Precision Medicine Consortium;Auer PL;Kooperberg C;Laurie CC;Blackwell TW;Smith AV;Zhao H;Lange E;Lange L;Rich SS;Rotter JI;Wilson JG;Scheet P;Kitzman JO;Lander ES;Engreitz JM;Ebert BL;Reiner AP;Jaiswal S;Abecasis G;Sankaran VG;Kathiresan S;Natarajan P
通讯作者：
Natarajan P
DOI：
10.1016/j.mrfmmm.2011.05.001
发表时间：
2012-02-01
影响因子：
2.3
作者：
Aviv, Abraham
通讯作者：
Aviv, Abraham