Systems biology and network pharmacology of frailty reveal novel epigenetic targets and mechanisms

被引:8
作者
Gomez-Verjan, J. C. [1 ]
Ramirez-Aldana, R. [1 ]
Perez-Zepeda, M. U. [1 ,2 ,3 ]
Quiroz-Baez, R. [1 ]
Luna-Lopez, A. [1 ]
Gutierrez Robledo, L. M. [1 ]
机构
[1] Inst Nacl Geriatria INGER, Mexico City, DF, Mexico
[2] Dalhousie Univ, Geriatr Med Res, Halifax, NS, Canada
[3] Nova Scotia Hlth Author, Halifax, NS, Canada
关键词
SKELETAL-MUSCLE; DNA METHYLATION; EXPRESSION; MYOSTATIN; MODULATION; CYTOSCAPE; AGE;
D O I
10.1038/s41598-019-47087-7
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Frailty is an age-associated condition, characterized by an inappropriate response to stress that results in a higher frequency of adverse outcomes (e.g., mortality, institutionalization and disability). Some light has been shed over its genetic background, but this is still a matter of debate. In the present study, we used network biology to analyze the interactome of frailty-related genes at different levels to relate them with pathways, clinical deficits and drugs with potential therapeutic implications. Significant pathways involved in frailty: apoptosis, proteolysis, muscle proliferation, and inflammation; genes as FN1, APP, CREBBP, EGFR playing a role as hubs and bottlenecks in the interactome network and epigenetic factors as HIST1H3 cluster and miR200 family were also involved. When connecting clinical deficits and genes, we identified five clusters that give insights into the biology of frailty: cancer, glucocorticoid receptor, TNF-alpha, myostatin, angiotensin converter enzyme, ApoE, interleukine-12 and -18. Finally, when performing network pharmacology analysis of the target nodes, some compounds were identified as potentially therapeutic (e.g., epigallocatechin gallate and antirheumatic agents); while some other substances appeared to be toxicants that may be involved in the development of this condition.
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页数:12
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