Understanding the senolytic and senomorphic effects of zoledronate treatment in an aging mouse model using spatial transcriptomics

Co-Investigators: James Edwards, University of Oxford; Eleanor Platt, Medicines Discovery Catapult

Bisphosphonates are commonly used to treat osteoporosis; however, treatment with bisphosphonates has also been shown to reduce the incidence of cancers, cardiovascular disease and mortality. The mechanisms underlying these effects are not fully understood; however, the proposed senolytic and senomorphic actions of bisphosphonates may play a role in destroying senescent cells and inhibiting the secretion of senescence-associated secretory phenotype (SASP) within aging tissue.

To investigate the effects of bisphosphonate treatment in vivo, tissue has been harvested from an aging mouse model treated with either bisphosphonates or vehicle over 8 weeks. Spatial transcriptomic analysis will be performed on various tissues harvested from these mice, focusing on the expression of senescence-associated genes and SASP markers.

There are two main aims of this study;

1. To better understand the aging mouse model C57BL/6N for this and future therapeutic studies
2. To determine the effect of Zoledronate treatment across different tissues to investigate cell populations, pathway biomarkers and molecular mechanisms underlying the wide-ranging effects of Zoledronate treatment and to identify new or repositioned drugs as potential therapeutics for age-related diseases.

@MedDiscCat Medicines Discovery Catapult - YouTube https://md.catapult.org.uk