Multiomic survey of secondary senescence in peripheral tissues from atherosclerotic mice

National Institute On Aging

Investigators

Abstract

Global omics approaches to characterize changes in gene expression programs in senescent cells have become the gold standard. Consequently, we have utilized these resources to enhance our understanding of how senescent cells in one tissue or cell type may impact others. In Objective 1, we aimed to determine how senescent vascular smooth muscle cells (VSMCs) might influence macrophage function both within the atherosclerotic niche and beyond. To this end, we conducted a series of conditioned media transfer experiments, observing dynamic changes in macrophage phagocytic activity following exposure to senescent VSMC conditioned media. We plan to extend these studies to other macrophage functions, examining gene expression through RNA sequencing and protein changes via proteomics. In Objective 2, we aimed to determine how senescent cells in aged mice affect skeletal muscle function. Collaborating with partners, we analyzed RNA-seq data from young and old mice treated with senolytics to identify which muscle cell types were most susceptible to senescence gene expression and contributed to the negative effects of aging in muscle. Notably, treatment with senolytics improved frailty and forelimb grip strength while reducing senescence-associated signaling and gene expression patterns (Murray et al., Aging Cell 2025). Additionally, using deconvolution analysis, we found that senescence gene expression decreased across myonuclei, pericytes, fibro-adipogenic progenitors, and neural cells in mice treated with fisetin.