Transcriptomic alterations during ageing reflect the shift from cancer to degenerative diseases in the elderly.
Transcriptomic alterations during ageing reflect the shift from cancer to degenerative diseases in the elderly.
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DOI：
10.1038/s41467-017-02395-2
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发表时间：
2018-01-30
影响因子：
16.6
通讯作者：
Kaleta C
中科院分区：
文献类型：
--
作者：
Aramillo Irizar P;Schäuble S;Esser D;Groth M;Frahm C;Priebe S;Baumgart M;Hartmann N;Marthandan S;Menzel U;Müller J;Schmidt S;Ast V;Caliebe A;König R;Krawczak M;Ristow M;Schuster S;Cellerino A;Diekmann S;Englert C;Hemmerich P;Sühnel J;Guthke R;Witte OW;Platzer M;Ruppin E;Kaleta C
老龄化过程中的疾病流行病学显示，从癌症到退行性慢性疾病的转变是老年人死亡的主要原因。然而，目前还不清楚衰老的分子特征在多大程度上反映了这一现象。在这里，我们报告了一个保守的转录组签名老化的基础上从四个脊椎动物物种在四个组织的基因表达数据的识别。我们发现，与衰老相关的转录组变化遵循与退行性衰老疾病中观察到的转录改变相似的轨迹，但与癌症中观察到的转录组改变方向相反。我们证实在基因组水平上存在类似的拮抗作用，其中大多数增加癌症风险的共享风险等位基因降低慢性退行性疾病的风险，反之亦然。这些结果揭示了癌症和退行性衰老疾病之间的基本权衡，揭示了衰老过程中流行病学的显著变化。老龄化与死亡率从癌症到退行性疾病的明显转变有关。在这里，作者表明，与这种转变相一致，四种脊椎动物衰老过程中保守的转录改变与退行性疾病一致，但与癌症相反。
Disease epidemiology during ageing shows a transition from cancer to degenerative chronic disorders as dominant contributors to mortality in the old. Nevertheless, it has remained unclear to what extent molecular signatures of ageing reflect this phenomenon. Here we report on the identification of a conserved transcriptomic signature of ageing based on gene expression data from four vertebrate species across four tissues. We find that ageing-associated transcriptomic changes follow trajectories similar to the transcriptional alterations observed in degenerative ageing diseases but are in opposite direction to the transcriptomic alterations observed in cancer. We confirm the existence of a similar antagonism on the genomic level, where a majority of shared risk alleles which increase the risk of cancer decrease the risk of chronic degenerative disorders and vice versa. These results reveal a fundamental trade-off between cancer and degenerative ageing diseases that sheds light on the pronounced shift in their epidemiology during ageing. Ageing is associated with a pronounced shift in mortality from cancer to degenerative diseases. Here, the authors show that in concordance with this shift, conserved transcriptional alterations during ageing across four vertebrates align with degenerative diseases but are opposite to those in cancer.
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DOI：
10.4161/15384101.2014.950151
发表时间：
2014
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
de Magalhães JP
通讯作者：
de Magalhães JP
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
11.2
作者：
Fehringer G;Kraft P;Pharoah PD;Eeles RA;Chatterjee N;Schumacher FR;Schildkraut JM;Lindström S;Brennan P;Bickeböller H;Houlston RS;Landi MT;Caporaso N;Risch A;Amin Al Olama A;Berndt SI;Giovannucci EL;Grönberg H;Kote-Jarai Z;Ma J;Muir K;Stampfer MJ;Stevens VL;Wiklund F;Willett WC;Goode EL;Permuth JB;Risch HA;Reid BM;Bezieau S;Brenner H;Chan AT;Chang-Claude J;Hudson TJ;Kocarnik JK;Newcomb PA;Schoen RE;Slattery ML;White E;Adank MA;Ahsan H;Aittomäki K;Baglietto L;Blomquist C;Canzian F;Czene K;Dos-Santos-Silva I;Eliassen AH;Figueroa JD;Flesch-Janys D;Fletcher O;Garcia-Closas M;Gaudet MM;Johnson N;Hall P;Hazra A;Hein R;Hofman A;Hopper JL;Irwanto A;Johansson M;Kaaks R;Kibriya MG;Lichtner P;Liu J;Lund E;Makalic E;Meindl A;Müller-Myhsok B;Muranen TA;Nevanlinna H;Peeters PH;Peto J;Prentice RL;Rahman N;Sanchez MJ;Schmidt DF;Schmutzler RK;Southey MC;Tamimi R;Travis RC;Turnbull C;Uitterlinden AG;Wang Z;Whittemore AS;Yang XR;Zheng W;Buchanan DD;Casey G;Conti DV;Edlund CK;Gallinger S;Haile RW;Jenkins M;Le Marchand L;Li L;Lindor NM;Schmit SL;Thibodeau SN;Woods MO;Rafnar T;Gudmundsson J;Stacey SN;Stefansson K;Sulem P;Chen YA;Tyrer JP;Christiani DC;Wei Y;Shen H;Hu Z;Shu XO;Shiraishi K;Takahashi A;Bossé Y;Obeidat M;Nickle D;Timens W;Freedman ML;Li Q;Seminara D;Chanock SJ;Gong J;Peters U;Gruber SB;Amos CI;Sellers TA;Easton DF;Hunter DJ;Haiman CA;Henderson BE;Hung RJ;Ovarian Cancer Association Consortium (OCAC);PRACTICAL Consortium;Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON);Colorectal Transdisciplinary (CORECT) Study;African American Breast Cancer Consortium (AABC) and African Ancestry Prostate Cancer Consortium (AAPC)
通讯作者：
African American Breast Cancer Consortium (AABC) and African Ancestry Prostate Cancer Consortium (AAPC)
影响因子：
1.8
作者：
DEAN, RL;SCOZZAFAVA, J;BARTUS, RT
通讯作者：
BARTUS, RT
影响因子：
18.2
作者：
Campisi J
通讯作者：
Campisi J