# Causes of Immune Cell Senescence in Aging Humans

> **NIH NIH R21** · RBHS-NEW JERSEY MEDICAL SCHOOL · 2021 · $196,041

## Abstract

Cellular senescence is a stable proliferative arrest that is encountered by mammalian cells in response to cell
extrinsic and intrinsic stresses, such as telomere dysfunction. In mammals, this stress response not only
functions to suppress cancer development, but it also plays important roles during tissue repair and embryonic
development. Cellular senescence, therefore, evolved to benefit the organism. The persistence of senescent
cells in tissue, however, also has a substantial negative impact on health and fitness. For example, senescent
cells accumulate with advancing age in various mammalian tissues and this accumulation of senescent cells
has recently been show to be a major contributing factor to aging and the development of age-associated
pathologies in mice. The aging-associated accumulation of senescent cells, however, is surprising, given that
they can be efficiently cleared from tissue by innate and adapted immune responses under different
circumstances in young animals, such as during tissue repair, as well as during embryonic and cancer
development. One model that could explain why senescent cells accumulate with advancing age in
mammalian tissue is that immune cells themselves increasingly become senescent as we age, thereby
increasingly weakening immune responses that would otherwise clear senescent cells from aged tissue.
This proposal tests the hypothesis that aging causes various subsets of human circulating immune cells to
increasingly undergo telomere dysfunction-induced cellular senescence with advancing age, thereby resulting
in an age-associated overall loss of immune cell function. Using a novel technique to detect senescent cells by
flow cytometry, we propose to identify specific populations of human peripheral blood mononuclear cells
(PBMCs) that increasingly undergo cellular senescence with advancing age. Additionally, we will characterize
the transcriptome and epigenome of senescent PBMCs by RNA-seq and ATAC seq, respectively, not only to
better define the senescence state of specific PBMC populations, but also to uncover potential targets for
therapeutic interventions to modulate senescence responses of human PBMCs. Lastly, using
immunofluorescence analysis and ex-vivo cultures of human PBMCs, we will reveal the causes and functional
consequences of PBMC senescence in humans and test strategies to suppress them, with the overall goal of
reducing immune cell senescence, improving immune function, and suppressing age-associated diseases.

## Key facts

- **NIH application ID:** 10160743
- **Project number:** 5R21AG067368-02
- **Recipient organization:** RBHS-NEW JERSEY MEDICAL SCHOOL
- **Principal Investigator:** PATRICIA FITZGERALD-BOCARSLY
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $196,041
- **Award type:** 5
- **Project period:** 2020-05-15 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10160743

## Citation

> US National Institutes of Health, RePORTER application 10160743, Causes of Immune Cell Senescence in Aging Humans (5R21AG067368-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10160743. Licensed CC0.

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