Karimi Isaac, Olfati Parisa, Mohammed Layth Jasim, Kadhim Tarrad Jawad, Amshawee Ahmed M, Hussain Maryam A, Schiöth Helgi B
Laboratory for Computational Physiology, Department of Biology, Faculty of Science, Razi University, Kermanshah, Iran.
Department of Microbiology, College of Medicine, Babylon University, Hilla City, Iraq.
Front Aging. 2025 Jul 30;6:1618082. doi: 10.3389/fragi.2025.1618082. eCollection 2025.
Cellular senescence drives aging and disease by promoting inflammation and tissue dysfunction. The kidneys, highly susceptible to aging, worsen with hypertension, increasing chronic disease risk. Managing blood pressure with angiotensin-converting enzyme (ACE) inhibitors and natural bioactive peptides helps maintain kidney health. This study explores a kidney-associated aging network and algal peptides with renoprotective and anti-aging effects.
Senescence-associated genes from Human Ageing Genomic Resources (HAGR) were used to construct and analyze a protein-protein interaction (PPI) network, refining a kidney-related subset ACE, angiotensin II Receptor Type 1 (AGTR1), and angiotensin II Receptor Type 2 (AGTR2). Algal antihypertensive peptides were filtered out of the laboratory dataset of algal peptides, , and assessed for allergenicity, antigenicity, toxicity, and anti-aging potential via sequence similarity searches. Selected peptides were prepared for molecular docking, tested against kidney-aging targets, and visualized.
A senescence-associated PPI network revealed key aging-related proteins-IL1R, CD4, FN1, STAT3, CD45, APOE, CD44, ITGAM. CD8A, CD68, CDH1, ACE, AGTR1, and AGTR2-linked to inflammation, immunity, and fibrosis. Screening identified 54 antihypertensive peptides, among which seven were predicted to be non-allergenic and non-antigenic peptides, while six out of them exhibited anti-aging properties. KTFPY and others exhibited strong binding to ACE and kidney-aging proteins, suggesting therapeutic benefits.
The senescence-associated PPI network reveals potentially important aging-related proteins affecting kidney health. Algal peptides, particularly KTFPY, VYRT, PGDTY, PVAFN, and MTFF, exhibit strong ACE binding, suggesting potential antihypertensive and anti-aging benefits. CD68 expressed reliable binding affinities with small-molecule ACE inhibitors, and it indicated the repurposing potential of these drugs for aging-associated conditions. These computational results highlight the potential of peptide-based therapies in addressing age-related kidney dysfunction, and warrant further experimental investigations.
细胞衰老通过促进炎症和组织功能障碍来推动衰老和疾病的发展。肾脏极易受到衰老影响，会因高血压而恶化，从而增加患慢性病的风险。使用血管紧张素转换酶（ACE）抑制剂和天然生物活性肽来控制血压有助于维持肾脏健康。本研究探索了一个与肾脏相关的衰老网络以及具有肾脏保护和抗衰老作用的藻类肽。
利用来自人类衰老基因组资源（HAGR）的衰老相关基因构建并分析蛋白质-蛋白质相互作用（PPI）网络，优化出一个与肾脏相关的子集，包括ACE、血管紧张素II 1型受体（AGTR1）和血管紧张素II 2型受体（AGTR2）。从藻类肽的实验室数据集中筛选出藻类降压肽，并通过序列相似性搜索评估其致敏性、抗原性、毒性和抗衰老潜力。对选定的肽进行分子对接准备，针对肾脏衰老靶点进行测试并可视化。
一个衰老相关的PPI网络揭示了关键的衰老相关蛋白——白细胞介素1受体（IL1R）、CD4、纤连蛋白1（FN1）、信号转导和转录激活因子3（STAT3）、CD45、载脂蛋白E（APOE）、CD44、整合素αM（ITGAM）、CD8A、CD68、钙黏蛋白1（CDH1）、ACE、AGTR1和AGTR2，这些蛋白与炎症、免疫和纤维化相关。筛选出54种降压肽，其中7种被预测为非致敏性和非抗原性肽，其中6种具有抗衰老特性。KTFPY等与ACE和肾脏衰老蛋白表现出强烈结合，显示出治疗益处。
衰老相关的PPI网络揭示了可能影响肾脏健康的重要衰老相关蛋白。藻类肽，特别是KTFPY、VYRT、PGDTY、PVAFN和MTFF，表现出与ACE的强烈结合，表明具有潜在的降压和抗衰老益处。CD68与小分子ACE抑制剂表现出可靠的结合亲和力，这表明这些药物在治疗与衰老相关疾病方面具有重新利用的潜力。这些计算结果突出了基于肽的疗法在解决与年龄相关的肾脏功能障碍方面的潜力，值得进一步的实验研究。
