The sculpting of somatic mutational landscapes by evolutionary forces and their impacts on aging-related disease.
The sculpting of somatic mutational landscapes by evolutionary forces and their impacts on aging-related disease.
复制标题
DOI：
10.1002/1878-0261.13275
复制
发表时间：
2022-09
影响因子：
6.6
通讯作者：
DeGregori, James
中科院分区：
文献类型：
--
作者：
Marongiu, Fabio;DeGregori, James
衰老是癌症和许多其他疾病发展的主要风险因素。最近的发现表明，正常组织中充满了扩增的克隆，这些克隆经常是由癌症相关突变以一种依赖年龄的方式驱动的。更多的研究表明，老化的组织微环境如何促进恶性肿瘤的发生和发展，而年轻的健康组织则积极抑制恶性克隆的生长。在这里，我们讨论保守的机制，从我们的组织中消除功能不佳或潜在的恶性细胞，以维持组织的健康和健身。自然选择的作用是保护组织功能和预防疾病，以最大限度地实现生殖成功，但随着生殖可能性的降低，这些机制逐渐消失。随之而来的与年龄相关的组织衰退可能会影响克隆体细胞进化的形状和方向，生活方式和暴露会影响其速度和强度。我们还考虑了依赖于衰老和暴露的“致癌”突变的克隆性扩张如何可能在晚年增加癌症风险，并有助于组织衰退和非恶性疾病。尽管如此，我们仍然可以惊叹于我们的身体避免癌症和其他疾病的能力，尽管我们积累了数十亿带有癌症相关突变的细胞。致病的克隆性扩张可以促进和促进炎症，并有助于多种衰老疾病的发生。虽然这些克隆有时会直接导致恶性疾病，正如具有克隆性造血突变的白血病清楚地表明的那样，但证据也揭示了克隆扩张如何间接地导致癌症和非恶性疾病，例如通过促进炎症。
Aging represents the major risk factor for the development of cancer and many other diseases. Recent findings show that normal tissues become riddled with expanded clones that are frequently driven by cancer‐associated mutations in an aging‐dependent fashion. Additional studies show how aged tissue microenvironments promote the initiation and progression of malignancies, while young healthy tissues actively suppress the outgrowth of malignant clones. Here, we discuss conserved mechanisms that eliminate poorly functioning or potentially malignant cells from our tissues to maintain organismal health and fitness. Natural selection acts to preserve tissue function and prevent disease to maximize reproductive success but these mechanisms wane as reproduction becomes less likely. The ensuing age‐dependent tissue decline can impact the shape and direction of clonal somatic evolution, with lifestyle and exposures influencing its pace and intensity. We also consider how aging‐ and exposure‐dependent clonal expansions of “oncogenic” mutations might both increase cancer risk late in life and contribute to tissue decline and non‐malignant disease. Still, we can marvel at the ability of our bodies to avoid cancers and other diseases despite the accumulation of billions of cells with cancer‐associated mutations. Pathogenic clonal expansions can promote and be promoted by inflammation, and contribute to multiple diseases of aging. While these clones can sometimes directly contribute to malignant disease, as clearly demonstrated for leukemias with clonal hematopoiesis mutations, evidence also reveals how clonal expansions can contribute indirectly to cancers and non‐malignant diseases such as through the promotion of inflammation.
登录
查看更多内容
影响因子：
30.8
作者：
Busque L;Patel JP;Figueroa ME;Vasanthakumar A;Provost S;Hamilou Z;Mollica L;Li J;Viale A;Heguy A;Hassimi M;Socci N;Bhatt PK;Gonen M;Mason CE;Melnick A;Godley LA;Brennan CW;Abdel-Wahab O;Levine RL
通讯作者：
Levine RL
影响因子：
2.6
作者：
Roshan A;Jones PH
通讯作者：
Jones PH
在健康个体中预测急性髓样白血病的风险。
影响因子：
64.8
作者：
Abelson S;Collord G;Ng SWK;Weissbrod O;Mendelson Cohen N;Niemeyer E;Barda N;Zuzarte PC;Heisler L;Sundaravadanam Y;Luben R;Hayat S;Wang TT;Zhao Z;Cirlan I;Pugh TJ;Soave D;Ng K;Latimer C;Hardy C;Raine K;Jones D;Hoult D;Britten A;McPherson JD;Johansson M;Mbabaali F;Eagles J;Miller JK;Pasternack D;Timms L;Krzyzanowski P;Awadalla P;Costa R;Segal E;Bratman SV;Beer P;Behjati S;Martincorena I;Wang JCY;Bowles KM;Quirós JR;Karakatsani A;La Vecchia C;Trichopoulou A;Salamanca-Fernández E;Huerta JM;Barricarte A;Travis RC;Tumino R;Masala G;Boeing H;Panico S;Kaaks R;Krämer A;Sieri S;Riboli E;Vineis P;Foll M;McKay J;Polidoro S;Sala N;Khaw KT;Vermeulen R;Campbell PJ;Papaemmanuil E;Minden MD;Tanay A;Balicer RD;Wareham NJ;Gerstung M;Dick JE;Brennan P;Vassiliou GS;Shlush LI
通讯作者：
Shlush LI
影响因子：
56.9
作者：
Del Poggetto, Edoardo;Ho, I-Lin;Balestrieri, Chiara;Yen, Er-Yen;Zhang, Shaojun;Citron, Francesca;Shah, Rutvi;Corti, Denise;Diaferia, Giuseppe R.;Li, Chieh-Yuan;Loponte, Sara;Carbone, Federica;Hayakawa, Yoku;Valenti, Giovanni;Jiang, Shan;Sapio, Luigi;Jiang, Hong;Dey, Prasenjit;Gao, Sisi;Deem, Angela K.;Rose-John, Stefan;Yao, Wantong;Ying, Haoqiang;Rhim, Andrew D.;Genovese, Giannicola;Heffernan, Timothy P.;Maitra, Anirban;Wang, Timothy C.;Wang, Linghua;Draetta, Giulio F.;Carugo, Alessandro;Natoli, Gioacchino;Viale, Andrea
通讯作者：
Viale, Andrea
影响因子：
64.8
作者：
Claveria, Cristina;Giovinazzo, Giovanna;Torres, Miguel
通讯作者：
Torres, Miguel