Biological Analysis Core

The goal of the Biological Analysis Core (BAC) is to apply multi-modal single-cell and imaging technologies
toward developing an Atlas of Senescence in Murine Tissues in male and female mice across the lifespan in
multiple strains. Our team of aging and bioinformatics experts have extensive infrastructure and unique expertise
that is ideally suited to build a comprehensive map of murine cellular senescence, including its regulators, cellular
manifestations, and impact on cell communication within the tissue environment. To achieve this, we will develop
an integrated pipeline for tissue analysis using genomic, imaging, and computational methods to characterize
senescence with single-cell and/or spatial context. We will leverage the NIA Study of Longitudinal Aging in Mice
(SLAM) multi-strain mouse aging project, transgenic reporter and senescence-depleted mice, and extensive
single-cell datasets combined with novel transfer learning to yield cross-tissue identification of SnCs in
plasma/serum and multiple select tissues (chosen due to the prevalence of SnCs, their association with aging-
related pathologies in mice, and their inclusion in the Human SenNet Program). We propose the following
Specific Aims, which encompass a multi-tiered approach to screen and deeply characterize SnCs in murine
tissues across their lifespan:
Aim 1: Establish multi-modal profiling of aging mice and transgenic models to identify cell senescence
in murine tissues across lifespan and their impact on tissue physiology.
Aim 2: Generate single-cell transcriptomic and epigenomic sequencing atlases of mouse aging to
reveal tissue-specific SnC identities.
Aim 3: Determine the impact of SnCs in tissues on their neighboring cell ecosystems using imaging-
based phenotypic and spatial senescent mapping.

Grant Number: 5U54AG079779-04
NIH Institute/Center: NIH
Principal Investigator: Darren Baker