# TS21 Effects on Senescence/SASP in neurons, glia and cell-specific exosomes, and spread of phenotype in vitro

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2023 · $235,375

## Abstract

PROJECT SUMMARY
Down Syndrome (DS) is considered a disease of premature aging and confers a significant predisposition for
early development of Alzheimer’s disease (AD). Recent evidence links senescence and the senescence
associated secretory phenotype (SASP), by which senescence spreads to bystander cells, as mechanisms that
may be a cause or early consequence of AD pathologic changes. The present project is aimed at understanding
the contribution of senescence/SASP to DS using human postmortem tissue and will examine the major cell
types (neurons, astrocytes, and microglia), and synaptic terminals. Cell-specific extracellular vesicles
(EVs)/exosomes will simultaneously be isolated from each brain sample. My laboratory has developed methods
for flow cytometry analysis of brain cells and synaptosomes (resealed nerve terminals) prepared from human
and mouse model tissue that has been cryopreserved. Human cases will include Downs Syndrome cases with
comparison to aged controls and AD cases across disease stage.
Our working hypothesis is that the accelerated aging phenotype that accompanies DS alters senescence/SASP
pathways in ways distinct from mechanisms in typical late-onset AD. We expect in differential effects in different
brain cell types, and hypothesize spread to neighboring cells by exosomes. Aim 1 will determine effects of
senescence/SASP in glia (microglia, astrocytes), and in neurons. Aim 2 is in vitro, and will examine effects of
DS on: a) senescence cargoes in cell-specific EVs/exosomes from human samples b) transfer of the senescence
phenotype in cell lines and co-cultures. Senolytics and other therapies are being considered, and the proposed
experiments in brain cell types and synapses are needed in order to understand mechanisms in human samples
and predict effects of these therapeutics. EV/exosome studies will address crucial gaps in basic science
understanding of EV transfer of phenotypes and pathology, and may serve as biomarkers for diagnosis and
disease progression.

## Key facts

- **NIH application ID:** 10657168
- **Project number:** 1R21AG082014-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Tina Bilousova
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $235,375
- **Award type:** 1
- **Project period:** 2023-06-15 → 2023-06-16

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10657168

## Citation

> US National Institutes of Health, RePORTER application 10657168, TS21 Effects on Senescence/SASP in neurons, glia and cell-specific exosomes, and spread of phenotype in vitro (1R21AG082014-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10657168. Licensed CC0.

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