Computational drug screening identifies compounds targeting renal age-associated molecular profiles

In this study we generated a signature of renal age-associated genes (RAAGs) based on six different data sources including transcriptomics data as well as data extracted from scientific literature and dedicated databases. Protein abundance in renal tissue of the 634 identified RAAGs was studied next to the analysis of affected molecular pathways. RAAG expression profiles were furthermore analysed in a cohort of 63 CKD patients with available follow-up data to determine association with CKD progression. 23 RAAGs were identified showing concordant regulation in renal aging and CKD progression. This set was used as input to computationally screen for compounds with the potential of reversing the RAAG/CKD signature on the transcriptional level. Among the top-ranked drugs we identified atorvastatin, captopril, valsartan, and rosiglitazone, which are widely used in clinical practice for the treatment of patients with renal and cardiovascular diseases. Their positive impact on the RAAG/CKD signature could be validated in an in-vitro model of renal aging.In summary, we have (i) consolidated a set of RAAGs, (ii) determined a subset of RAAGs with concordant regulation in CKD progression, and (iii) identified a set of compounds capable of reversing the proposed RAAG/CKD signature.Graphical abstract
Source: Computational and Structural Biotechnology Journal - Category: Biotechnology Source Type: research

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Source: Experimental and Therapeutic Medicine - Category: General Medicine Tags: Exp Ther Med Source Type: research
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Source: Arteriosclerosis, Thrombosis and Vascular Biology - Category: Cardiology Authors: Tags: Arterioscler Thromb Vasc Biol Source Type: research
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Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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Source: Expert Opinion on Pharmacotherapy - Category: Drugs & Pharmacology Tags: Expert Opin Pharmacother Source Type: research
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Source: Postgraduate Medicine - Category: Internal Medicine Tags: Postgrad Med Source Type: research
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Source: American Journal of Cardiovascular Drugs - Category: Cardiology Source Type: research
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Source: Scandinavian Cardiovascular Journal - Category: Cardiology Tags: Scand Cardiovasc J Source Type: research
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