Immunoinformatic-based drug design utilizing hesperetin to target CISD2 activation for liver aging in humans.

Abstract

The CISD protein family, consisting of CISD1, CISD2, and CISD3, encodes proteins that feature CDGSH iron-sulfur domains crucial for cellular functions and share a common 2Fe-2S domain. CISD2, which is pivotal in cells, regulates intracellular calcium levels, maintains the endoplasmic reticulum and mitochondrial function, and is associated with longevity and overall health, with exercise stimulating CISD2 production. However, CISD2 expression decreases with age, impacting age-related processes. According to in silico docking, HST is a CISD2 activator that affects metabolic dysfunction and age-related illnesses by affecting metabolic pathways. This study investigated the ability of CISD2 and HST to reduce age-related ailments, with a particular emphasis on liver aging. CISD2 deficiency has a major effect on the function of cells, as it undermines the integrity of the ER, mitochondria, and calcium homeostasis. It also increases susceptibility to oxidative stress and metabolic dysregulation, which is linked to Wolfram syndrome and exacerbates age-related illnesses and metabolic disorders. By shielding cells from stress, CISD2 extends the life of cells and maintains liver health as people age. Its protective effecfts on the liver during aging are further enhanced by its control of translation factors such as Nrf2 and IL-6. This work paves the way for future investigations and clinical applications by examining the structural and functional properties of CISD2 and the interaction between CISD2 and HST. This highlights the therapeutic potential of these findings in promoting healthy livers in humans and battling age-related illnesses.