Molecular Modeling Studies to Probe the Age Reversal Potential of Thyme (Thymus serpyllum)

Abstract

oncept of a 'fountain of youth' reflects humanity's persistent desire to slow aging. Aging naturally impacts organ function, resulting in age-related diseases.Telomeres protect chromosomal ends, but they shorten with each cell division, contributing to aging and diseases such as diabetes, hypertension, alzheimer's, and cancer. Activating human telomerase reverse transcriptase (hTERT) can increase telomere length and potentially reverse aging effects. Hyper-activation of hTERT can cause cancer, therefore it is critical to balance hTERT and p53 activity for cell proliferation and apoptosis. Telomerase gene therapy in mice increased health markers and extended lifespans without raising cancer risk, showing potential for promoting longevity and improving quality of life. A biological regulatory network (BRN) previously identified Sp1's dual function in activating both p53 and hTERT, demonstrating an association between Sp1 activity and variations of p53 and hTERT. The model proved that the normal, moderately active, and hyperactive states of Sp1 which are required to maintain normal cell proliferation and apoptosis have been associated with corresponding variations in hTERT and p53 concentrations. The purpose of this study is to probe extracts from Thymus serpyllum, a plant associated with the long-living Hunza people, in order to find bioactive compounds that can reverse aging. After extraction with n-Hexane, methanol, ethyl acetate, and chloroform, several compounds were identified by Gas chromatography-mass spectrometry analysis. Previously the protein –protein docking with up-regulators of both P53 and h-TERT showed that the binding site residues of hTERT Arg-224 and Arg-535 showed hydrogen bonding in c Myc-hTERT complex before and after MD simulation. Ser-227 and Ala-228 showed the stable hydrogen bonding before and after MD simulation in STAT3-hTERT complex. Arg-224 formed the salt bridges in c-Myc-hTERT complex. The binding site residues of p53 Arg 158, Arg 267 showed hydrogen bonding in Phf20-p53 complex before and after simulation, in p300-p53 complex Arg-158 formed the salt bridges. In the present study the Thymus serpyllum plant compounds were docked against the p53 and hTERT proteins, the results showed that important over-lapping xi residues p53 Arg-158, Arg-267and for h-TERT Arg-224, Arg-535, Ser-227, Ala-228 successfully bound the proteins. Hydrogen bond donor, acceptor, and surface contact interactions were verified by Protein ligand interaction fingerprint analysis. These results suggest that Thymus serpyllum compounds can up-regulate p53 and hTERT, providing the foundation for further experimental verification of their age-reversal properties.