# The anti-aging potential of antihypertensive peptides of Pariset, a dataset of algal peptides

**Authors:** Isaac Karimi, Parisa Olfati, Layth Jasim Mohammed, Jawad Kadhim Tarrad, Ahmed M. Amshawee, Maryam A. Hussain, Helgi B. Schiöth

PMC · DOI: 10.3389/fragi.2025.1618082 · 2025-07-30

## TL;DR

This paper explores algal peptides that may help reduce aging-related kidney damage by targeting inflammation and hypertension.

## Contribution

The study introduces a dataset of algal peptides with potential anti-aging and renoprotective properties identified through computational analysis.

## Key findings

- A senescence-associated PPI network identified key proteins like IL1R, CD4, and ACE linked to kidney aging.
- 54 antihypertensive peptides were identified, with seven being non-allergenic and six showing anti-aging properties.
- Peptides like KTFPY and VYRT showed strong binding to ACE and kidney-aging proteins, suggesting therapeutic potential.

## Abstract

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, Pariset, 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.

## Linked entities

- **Genes:** IL1R1 (interleukin 1 receptor type 1) [NCBI Gene 3554], CD4 (CD4 molecule) [NCBI Gene 920], FN1 (fibronectin 1) [NCBI Gene 2335], STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774], PTPRC (protein tyrosine phosphatase receptor type C) [NCBI Gene 5788], APOE (apolipoprotein E) [NCBI Gene 348], CD44 (CD44 molecule (IN blood group)) [NCBI Gene 960], ITGAM (integrin subunit alpha M) [NCBI Gene 3684], CD8A (CD8 subunit alpha) [NCBI Gene 925], CD68 (CD68 molecule) [NCBI Gene 968], CDH1 (cadherin 1) [NCBI Gene 999], ACE (angiotensin I converting enzyme) [NCBI Gene 1636], AGTR1 (angiotensin II receptor type 1) [NCBI Gene 185], AGTR2 (angiotensin II receptor type 2) [NCBI Gene 186]
- **Proteins:** ACE (angiotensin I converting enzyme), AGTR1 (angiotensin II receptor type 1), AGTR2 (angiotensin II receptor type 2), IL1R1 (interleukin 1 receptor type 1), CD4 (CD4 molecule), FN1 (fibronectin 1), STAT3 (signal transducer and activator of transcription 3), PTPRC (protein tyrosine phosphatase receptor type C), APOE (apolipoprotein E), CD44 (CD44 molecule (IN blood group)), ITGAM (integrin subunit alpha M), CD8A (CD8 subunit alpha), CD68 (CD68 molecule), CDH1 (cadherin 1)

## Full-text entities

- **Genes:** AGT (angiotensinogen) [NCBI Gene 183] {aka ANHU, SERPINA8, hFLT1}, FGB (fibrinogen beta chain) [NCBI Gene 2244] {aka HEL-S-78p}, JAK1 (Janus kinase 1) [NCBI Gene 3716] {aka AIIDE, JAK1A, JAK1B, JTK3}, IL12B (interleukin 12B) [NCBI Gene 3593] {aka CLMF, CLMF2, IL-12B, IMD28, IMD29, NKSF}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, ITGB2 (integrin subunit beta 2) [NCBI Gene 3689] {aka CD18, LAD, LCAMB, LFA-1, MAC-1, MF17}, IL1RN (interleukin 1 receptor antagonist) [NCBI Gene 3557] {aka CRMO2, DIRA, ICIL-1RA, IL-1RN, IL-1ra, IL-1ra3}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, JAK2 (Janus kinase 2) [NCBI Gene 3717] {aka JTK10}, CD68 (CD68 molecule) [NCBI Gene 968] {aka GP110, LAMP4, SCARD1}, Il31 (interleukin 31) [NCBI Gene 76399] {aka 1700013B14Rik}, CD44 (CD44 molecule (IN blood group)) [NCBI Gene 960] {aka CDW44, CSPG8, ECM-III, ECMR-III, H-CAM, HCELL}, MAPK3 (mitogen-activated protein kinase 3) [NCBI Gene 5595] {aka ERK-1, ERK1, ERT2, HS44KDAP, HUMKER1A, P44ERK1}, AGTR2 (angiotensin II receptor type 2) [NCBI Gene 186] {aka AT2, ATGR2, MRX88}, APOE (apolipoprotein E) [NCBI Gene 348] {aka AD2, APO-E, ApoE4, LDLCQ5, LPG}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, CDH1 (cadherin 1) [NCBI Gene 999] {aka Arc-1, BCDS1, CD324, CDHE, ECAD, LCAM}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, FN1 (fibronectin 1) [NCBI Gene 2335] {aka CIG, ED-B, FINC, FN, FNZ, GFND}, ITCH (itchy E3 ubiquitin protein ligase) [NCBI Gene 83737] {aka ADMFD, AIF4, AIP4, NAPP1}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, SNAI1 (snail family transcriptional repressor 1) [NCBI Gene 6615] {aka SLUGH2, SNA, SNAH, SNAIL, SNAIL1, dJ710H13.1}, CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}, CAMP (cathelicidin antimicrobial peptide) [NCBI Gene 820] {aka CAP-18, CAP18, CRAMP, FALL-39, FALL39, HSD26}, SLC5A2 (solute carrier family 5 member 2) [NCBI Gene 6524] {aka SGLT2}, ICAM1 (intercellular adhesion molecule 1) [NCBI Gene 3383] {aka BB2, CD54, P3.58}, EP300 (EP300 lysine acetyltransferase) [NCBI Gene 2033] {aka KAT3B, MKHK2, RSTS2, p300}, Stat3 (signal transducer and activator of transcription 3) [NCBI Gene 20848] {aka 1110034C02Rik, Aprf}, STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774] {aka ADMIO, ADMIO1, APRF, HIES}, CBLL1 (Cbl proto-oncogene like 1) [NCBI Gene 79872] {aka HAKAI, RNF188}, FYN (FYN proto-oncogene, Src family tyrosine kinase) [NCBI Gene 2534] {aka SLK, SYN, p59-FYN}, PTPRU (protein tyrosine phosphatase receptor type U) [NCBI Gene 10076] {aka FMI, PCP-2, PTP, PTP-J, PTP-PI, PTP-RO}, SKAP1 (src kinase associated phosphoprotein 1) [NCBI Gene 8631] {aka HEL-S-81p, SCAP1, SKAP55}, PDB [NCBI Gene 5131], LYN (LYN proto-oncogene, Src family tyrosine kinase) [NCBI Gene 4067] {aka JTK8, SAIDV, p53Lyn, p56Lyn}, ITGAM (integrin subunit alpha M) [NCBI Gene 3684] {aka CD11B, CR3A, HNA-4, MAC-1, MAC1A, MO1A}, DPP4 (dipeptidyl peptidase 4) [NCBI Gene 1803] {aka ADABP, ADCP2, CD26, DPPIV, TP103}, REN (renin) [NCBI Gene 5972] {aka ADTKD4, HNFJ2, RTD}, AP2B1 (adaptor related protein complex 2 subunit beta 1) [NCBI Gene 163] {aka ADTB2, AP105B, AP2-BETA, CLAPB1}, WRN (WRN RecQ like helicase) [NCBI Gene 7486] {aka RECQ3, RECQL2, RECQL3}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, GLB1 (galactosidase beta 1) [NCBI Gene 2720] {aka EBP, ELNR1, MPS4B}, ACE (angiotensin I converting enzyme) [NCBI Gene 1636] {aka ACE1, CD143, DCP, DCP1}, HSP90AA1 (heat shock protein 90 alpha family class A member 1) [NCBI Gene 3320] {aka EL52, HEL-S-65p, HSP86, HSP89A, HSP90A, HSP90N}, PTPRC (protein tyrosine phosphatase receptor type C) [NCBI Gene 5788] {aka B220, CD45, CD45R, GP180, IMD105, L-CA}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, Fn1 (fibronectin 1) [NCBI Gene 14268] {aka E330027I09, Fn, Fn-1}, IL1R1 (interleukin 1 receptor type 1) [NCBI Gene 3554] {aka CD121A, CRMO3, D2S1473, IL-1R-alpha, IL-1RT1, IL1R}, TXK (TXK tyrosine kinase) [NCBI Gene 7294] {aka BTKL, PSCTK5, PTK4, RLK, TKL}, GLP1R (glucagon like peptide 1 receptor) [NCBI Gene 2740] {aka GLP-1, GLP-1-R, GLP-1R}, GCG (glucagon) [NCBI Gene 2641] {aka GLP-1, GLP1, GLP2, GRPP}, SRC (SRC proto-oncogene, non-receptor tyrosine kinase) [NCBI Gene 6714] {aka ASV, SRC1, THC6, c-SRC, p60-Src}, C3 (complement C3) [NCBI Gene 718] {aka AHUS5, ARMD9, ASP, C3a, C3b, CPAMD1}, CDK5R2 (cyclin dependent kinase 5 regulatory subunit 2) [NCBI Gene 8941] {aka NCK5AI, P39, p39nck5ai}, AGTR1 (angiotensin II receptor type 1) [NCBI Gene 185] {aka AG2S, AGTR1B, AT1, AT1AR, AT1B, AT1BR}, PTPN22 (protein tyrosine phosphatase non-receptor type 22) [NCBI Gene 26191] {aka LYP, LYP1, LYP2, PEP, PTPN22.5, PTPN22.6}, CRIPTO3 (cripto, EGF-CFC family member 3) [NCBI Gene 6998] {aka CR-3, CRIPTO-3, TDGF1, TDGF1P3, TDGF2, TDGF3}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}
- **Diseases:** lymphoid tumor metastasis (MESH:D009362), glomerulopathies (MESH:D007674), malaria (MESH:D008288), Toxicity (MESH:D064420), bacterial infection (MESH:D001424), liver cirrhosis (MESH:D008103), age-related disorders (MESH:D008569), atrophy (MESH:D001284), cancer (MESH:D009369), diabetic nephropathy (MESH:D003928), CKD (MESH:D051436), fibrosis (MESH:D005355), dizziness (MESH:D004244), glomerulosclerosis (MESH:D005921), kidney function (MESH:D007680), heart failure (MESH:D006333), HDGC (MESH:D013274), Hypertension (MESH:D006973), cleft lip/palate (MESH:D002971), focal segmental glomerulosclerosis (MESH:D005923), dry cough (MESH:D003371), REC (MESH:D002292), heart disease (MESH:D006331), chronic diseases (MESH:D002908), pulmonary fibrosis (MESH:D011658), cardiovascular disease (MESH:D002318), autoinflammatory syndromes (MESH:D056660), fibrotic diseases (MESH:D004194), lobular breast cancer (MESH:D001943), neurodegenerative diseases (MESH:D019636), stroke (MESH:D020521), hypersensitivity (MESH:D004342), proteinuria (MESH:D011507), fracture (MESH:D050723), inflammation (MESH:D007249)
- **Chemicals:** lipid (MESH:D008055), prostaglandins (MESH:D011453), Benazepril (MESH:C044946), navitoclax (MESH:C528561), ACEIs (-), canakinumab (MESH:C541220), Losartan (MESH:D019808), captopril (MESH:D002216), hydrogen (MESH:D006859), Trandolapril (MESH:C052035), water (MESH:D014867), reactive oxygen species (MESH:D017382), A6 (MESH:C043832), quercetin (MESH:D011794), lisinopril (MESH:D017706), BAs (MESH:D001464), potassium (MESH:D011188), ramipril (MESH:D017257), heparin (MESH:D006493), Moexipril Hydrochloride (MESH:C058302), Quinapril (MESH:D000077583), E-3174 (MESH:C066026), enalapril (MESH:D004656), hyaluronan (MESH:D006820), dasatinib (MESH:D000069439), aldosterone (MESH:D000450), fisetin (MESH:C017875)
- **Species:** Pyropia pseudolinearis (species) [taxon 81939], Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606], PX clade (clade) [taxon 569578], Rattus norvegicus (brown rat, species) [taxon 10116], Gracilariopsis lemaneiformis (species) [taxon 2782], Acrochaetium sp. (species) [taxon 2020008]
- **Cell lines:** -2 — Homo sapiens (Human), Colon carcinoma, Cancer cell line (CVCL_A628)

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12343563/full.md

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Source: https://tomesphere.com/paper/PMC12343563