# Lipid signaling in cellular senescence and tissue aging

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 2020 · $366,545

## Abstract

Abstract
 This proposal is focused on the challenge of understanding and thus improving treatment for
idiopathic pulmonary fibrosis, a devastating interstitial lung disease without effective treatments.
Deregulation of lipid signaling and metabolism has long been studied in pulmonary fibrosis, pointing
to changes in sphingolipid and ceramide pathways that may impact pathology. In recent years,
increased attention has been paid to a possible role for senescent cells in the lung as a critical factor
driving pulmonary fibrosis. Senescent cells express inflammatory factors, including signaling lipids,
which may drive the fibrotic process. Current questions include why senescent cells accumulate in
these patients and how their pro-inflammatory activity might be mitigated. An inference is that
preventing formation of senescent cells, blocking their lipid signaling and/or promoting their clearance
from the lung might prevent pulmonary fibrosis or block disease progression.
 Importantly, there may be a direct link between sphingolipid pathways and cellular senescence.
Ceramides have been shown to induce senescence in otherwise proliferating cells. Our studies have
implicated lipid peroxidation and its aldehyde end-products such as 4-hydroxynonenal as key
mediators of accelerated senescence. Transcriptomic, proteomic and lipidomic analysis of
proliferative and senescent lung cells will be used to identify key senescence factors and networks
that may point to the specific lipid metabolic pathways that drive senescence and inflammatory
signaling. We will then examine lipids and modulators for the ability to promote or prevent
senescence. Finally, we will examine whether manipulation of lipid metabolic pathways can be used
to potentiate clearance of senescent cells and thereby limit pulmonary fibrosis. With success in these
studies, we anticipate identification of candidate therapeutics with potential to move to clinical trials.

## Key facts

- **NIH application ID:** 10095615
- **Project number:** 1R01AG069865-01
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Stephen J. Kron
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $366,545
- **Award type:** 1
- **Project period:** 2020-09-15 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10095615

## Citation

> US National Institutes of Health, RePORTER application 10095615, Lipid signaling in cellular senescence and tissue aging (1R01AG069865-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10095615. Licensed CC0.

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