Biological mechanisms of aging predict age-related disease co-occurrence in patients.
Biological mechanisms of aging predict age-related disease co-occurrence in patients.
复制标题
作者：
对衰老过程的遗传、环境和药物干预可以使实验动物对多种与年龄相关的疾病产生抵抗力，包括恒河猴。这些发现表明，个体衰老机制可能有助于人类共同发生与年龄相关的疾病，并可能有针对性地同时预防这些疾病。为了解决这个问题，我们对917,645个文献摘要进行了文本挖掘，然后进行了手动整理，发现了与年龄相关的疾病与人类衰老机制之间的强烈、非随机关联，这一点得到了GWAS数据的基因集浓缩分析的证实。将这些关联与301万名患者的临床数据整合在一起表明，与五种衰老机制中的每一种相关的年龄相关疾病更有可能出现在患者身上，而不是偶然出现。遗传证据表明，天然免疫和获得性免疫、固有的细胞凋亡信号通路和ERK1/2通路的活性与多种衰老机制和多种老年性疾病有关。因此，衰老机制共同和单独地促进了与年龄相关的疾病在人类中的共同发生，并可能相应地成为预防多发病的靶点。通过文本挖掘、基因集浓缩和网络分析，我们发现五个衰老特征(营养感知失调、线粒体功能障碍、细胞衰老、干细胞耗竭和细胞间通讯改变)与年龄相关疾病的共同发生有关。先天和获得性免疫、RAS-ERK和固有的凋亡信号通路在所有9个衰老标志中都得到了丰富，这表明通过靶向这些通路可以预防多种疾病。
Genetic, environmental, and pharmacological interventions into the aging process can confer resistance to multiple age‐related diseases in laboratory animals, including rhesus monkeys. These findings imply that individual mechanisms of aging might contribute to the co‐occurrence of age‐related diseases in humans and could be targeted to prevent these conditions simultaneously. To address this question, we text mined 917,645 literature abstracts followed by manual curation and found strong, non‐random associations between age‐related diseases and aging mechanisms in humans, confirmed by gene set enrichment analysis of GWAS data. Integration of these associations with clinical data from 3.01 million patients showed that age‐related diseases associated with each of five aging mechanisms were more likely than chance to be present together in patients. Genetic evidence revealed that innate and adaptive immunity, the intrinsic apoptotic signaling pathway and activity of the ERK1/2 pathway were associated with multiple aging mechanisms and diverse age‐related diseases. Mechanisms of aging hence contribute both together and individually to age‐related disease co‐occurrence in humans and could potentially be targeted accordingly to prevent multimorbidity. Using text‐mining, gene set enrichment and network analysis, we found that five aging hallmarks (deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion and altered intercellular communication) were associated with co‐occurrence of age‐related diseases. Innate and adaptive immunity, Ras‐ERK and intrinsic apoptotic signalling pathways were enriched for all nine aging hallmarks, indicating that multiple diseases may be prevented by targeting these pathways.
登录
查看更多内容
DOI：
10.1093/bioinformatics/btv301
发表时间：
2015-09-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Gutiérrez-Sacristán A;Grosdidier S;Valverde O;Torrens M;Bravo À;Piñero J;Sanz F;Furlong LI
通讯作者：
Furlong LI
影响因子：
7.7
作者：
Austad SN;Hoffman JM
通讯作者：
Hoffman JM
Biopython：用于计算分子生物学和生物信息学的免费 Python 工具。
DOI：
10.1093/bioinformatics/btp163
发表时间：
2009-06-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Cock PJ;Antao T;Chang JT;Chapman BA;Cox CJ;Dalke A;Friedberg I;Hamelryck T;Kauff F;Wilczynski B;de Hoon MJ
通讯作者：
de Hoon MJ
影响因子：
14.9
作者：
NCBI Resource Coordinators
通讯作者：
NCBI Resource Coordinators
DOI：
10.1016/s0735-1097(00)00611-2
发表时间：
2000-05-01
影响因子：
24
作者：
Goette, A;Staack, T;Lendeckel, U
通讯作者：
Lendeckel, U