Validation of novel senescence biomarkers and frailty index implementation in naturally aged C57BL/6 mice combined with the senolytic potential of Artemisinin and its derivatives measured in a human senescence model

Global demographic changes will shift the population to be older, which will be associated with increased costs for pensions and healthcare. To reduce healthcare costs and improve the quality of life for the elderly, research into aging and potential interventions has significantly grown. This project focuses on senescence, one of the several hallmarks of aging. It is a necessary cell fate, but as we age, their lack of clearance by immune cells results in a senescent cell burden, contributing to age-related disease and decline. The project goals included the validation of senescent models using established markers for preparation of senolytic studies using Artemisinin and its derivatives. The testing of novel biomarkers Cy7-Gal and Gal-NB in vitro, ex vivo and in vivo of naturally aged C57BL/6 mice. The implementation of a frailty index to provide a holistic view of mice health in potential senolytic studies in vivo.

The testing of Artemisinin and its derivatives in IMR-90 and A549 cells did not produce a senolytic effect throughout, contradicting literary evidence in murine and cancer senescence whereby the derivatives Artesunate and Dihydroartemisinin functioned as senolytics. This novel finding is important in the context of senescence as it highlights the heterogeneity present and difficulty in generating a senolytic to function across cell types and differing induction methods. The testing of Cy7-Gal and Gal-NB to track senescence in vivo over time in naturally aged C57BL/6 mice was unsuccessful. This evidence highlights the challenge of generating novel senescence biomarkers that can identify senescence in naturally-aged subjects. The implementation of a frailty index using data from open field testing, rotarod, and grip strength proved complicated, resulting in the generation of a perspective accepted for publication that analyses the current state of frailty indexes, highlights the difficulties of its implementation and concludes with recommendations for aging studies that wish to utilise frailty indexes.