# TriState SenNET (Lung and Heart) Tissue Map and Atlas consortium

> **NIH NIH U54** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2022 · $2,700,000

## Abstract

Senescent cells accumulate with age and are increasingly linked to a variety of age-related diseases. At present,
senescent cells are operationally characterized based on a set of morphological, biochemical, and molecular
properties. However, senescence is unlikely to represent a single uniform entity. Rather, analogous to what has
been learned from studying tumors, the cell type, in conjunction with the specific endogenous driver of
senescence, will likely determine the unique molecular fingerprint of a given senescent cell. Understanding this
fingerprint, like our understanding of the specific genetic alterations in a given tumor, will, in turn, inform prognosis
and response to therapy. Much of our understanding of the biology of senescence has come from experimental
animal models, while our understanding of senescence in human cells and tissues remains, at best, incomplete.
Similarly, while a number of exogenous stresses can trigger a senescent phenotype for cells in culture, the
physiological relevant drivers of human senescence are not known. Finally, while for proliferating cells,
senescence is characterized by a permanent withdrawal from the cell cycle, the relevant senescent cell markers
and biology for critical post-mitotic cells (e.g., cardiac myocytes, neurons) is not well established. To begin to
address these significant knowledge gaps, the TriState SenNet Tissue Mapping Center (TMC) will analyze
human lung and heart tissue to provide a high-resolution map of the senescent cell population in these organs.
With the combined expertise of the University of Pittsburgh and Carnegie Mellon University, Ohio State
University, and the University of Rochester School of Medicine, this consortium will provide a comprehensive
assessment of two organs linked to a variety of age-related diseases, one of which is largely post-mitotic. Our
analysis will involve in situ mapping using established targeted assays, as well as high-content unbiased
approaches involving single cell RNA/ATAC sequencing, proteomics, and spatial transcriptomics. In addition, as
part of our mapping endeavor, the TriState SenNet TMC will analyze the relationship between the initiating
trigger for senescence and the subsequent biology and phenotype of the senescent cell. This relationship will
be probed using precision cut tissue sections from human lungs and hearts that will be perturbed ex vivo by
specific senescent triggers. This procedure will allow us to increase the precision and sensitivity of detection and
localization of senescent cells in the lung and heart. Finally, we will purify and isolate senescent and non-
senescent cells from an individual donor lung and used these isogenic primary cells to deconvolute the
physiologically relevant driver of human senescence and delineate the molecular basis for the observed
selectivity of senolytic therapy. Together, this combined analysis of tissue and tissue slices/cells from the same
individual will provide an unrivaled, unpr...

## Key facts

- **NIH application ID:** 10492689
- **Project number:** 5U54AG075931-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** TOREN FINKEL
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $2,700,000
- **Award type:** 5
- **Project period:** 2021-09-30 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10492689

## Citation

> US National Institutes of Health, RePORTER application 10492689, TriState SenNET (Lung and Heart) Tissue Map and Atlas consortium (5U54AG075931-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10492689. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*