DefinePK

Abstract

 Ageing and age-related diseases, including pancreatic cancer, are intricately linked to molecular disruptions that compromise cellular integrity and homeostasis. The REME1 gene, a novel hypothetical anti-ageing gene, is believed to be critical in mitigating these age-related processes. Mutations in REME1 critical binding pockets reduce expression, resulting in increased redox stress, telomere shortening, and impaired cellular repair mechanisms hallmarks of ageing that contribute to the onset of age-related diseases, particularly pancreatic cancer. This research explores the potential of Baicalein, a natural compound, as a therapeutic ligand to restore REME1 expression. In silicon docking studies show that Baicalein binds effectively to the mutated REME1 binding pockets, stabilizing its structure, and enhancing gene expression.  This work seeks to assess the probability of Baicalein, which is a flavonoid obtained from natural products, acting as a therapeutic ligand for the replacement of REME1. Baicalein shows promising binding characteristics with REME1 binding domains which were PDB-transformed sites thus implying good affinity. In alleviating these alterations, REME1 is fully restored and therefore possesses its three essential functions; compromising oxidative stress, maintaining the integrity of the telomeres, and aiding cellular repair mechanisms which in elevated levels may offer treatment for old age and other related disorders such as Pancreatic cancer. Upregulation of REME1 is further supported through key molecular pathways, including AMPK, Akt, NF-κB, TGF-β, LXRα, SREBP1, and the Warburg effect. It is observed that these pathways uniformly reduce oxidative stress, and NEFA metabolism, and enhance cellular operation. More importantly, when inflammation is modulated and mitochondria bioenergetics are altered, a most favourable outcome for energy intake and utilization appears by the upregulation of REME1. Thus, this upregulation targets ageing and age-related diseases including pancreatic cancer. In general, this type of research underscores the utility of REME1 in cancer and ageing therapies and its importance resulting from novel cancer strategies which are computational and thus grant grounds for possible further laboratory exploration.