Exploring the Promise of Anti-Senescence Drugs and Screening Platforms for Liver Health: A Comprehensive Review

Abstract

Chronic liver diseases remain a worldwide leading cause of mortality and morbidity. A link between the disease progression and burden of senescent cells in the organ has been established. There is a growing interest in assessing the effectiveness of anti-senescence drugs in liver diseases. However, despite the increased curiosity, a general review of the advances in the field was missing. We show the anti-senescence drugs and their testing setups, as well as present novel, promising drug-screening liver platforms. We found that despite a high number of anti-senescence agents, many of them were not tested specifically for liver disease. Our research concentrated on newly designed compounds specifically to target senescence, as well as repurposed drugs while providing background into intricacies of senescence as a highly ambivalent cellular process. The compounds were tested usually using two-dimensional cell lines or mice models, with little to no focus on three-dimensional in vitro setups. In these cases, we provided examples of novel liver experimental techniques such as organoids, spheroids, liver buds, organs-on-chip, and bioprinting, that could be applied to senescence research. The mechanisms of action of the described compounds varied greatly- with some of them not targeting senescence directly. Their testing platforms were mostly either too simple or too complex for the beginning stages of drug development. Given that liver disease is still highly undiagnosed, and its increasing prevalence is being prognosed, we believe that there is a need for physiologically relevant models that are also time and money-efficient for correct assessment of novel anti-senescence compounds.