# Progressive states of cell-cycle withdrawal

> **NIH NIH R01** · UNIVERSITY OF COLORADO · 2023 · $349,636

## Abstract

Project Summary
Senescence is the process by which a cell permanently stops proliferating due to cellular aging
or damage but does not die. Induction of senescence is often desirable during cancer treatment
to prevent the proliferation of aberrant cells, but it also impedes cellular function and
regenerative capacity as we age. The study of cellular senescence is hindered by the fact that
senescence is difficult to distinguish from other states of cell-cycle withdrawal such as
quiescence, a transient cellular resting state. This is because quiescence and senescence are
defined by overlapping molecular markers and because these cell-cycle transitions occur
heterogeneously from cell to cell. Despite obvious medical relevance, it is unclear whether
senescence and quiescence are truly distinct states. Here we propose to test the hypothesis
that senescence and quiescence exist on a continuum of cell-cycle withdrawal where the
probability of cell-cycle re-entry steadily declines toward zero as cells become senescent.
We will leverage our unique expertise in long-term, time-lapse microscopy, automated single-
cell tracking, and the development of sensors for cell-cycle progression and cell-cycle
withdrawal to unveil gradations of cell-cycle withdrawal that are invisible by standard bulk
approaches. Our specific aims are 1) To determine the predictive power of prevailing
senescence markers as binary markers of senescence and as graded markers of quiescence
depth, 2) To determine at the transcriptomic level whether quiescence and senescence are
distinct states or part of a continuum of cell-cycle withdrawal, and 3) To the identify the DNA
damage and telomere features that predict permanent cell-cycle withdrawal as cells age toward
replicative senescence.
If successful, this work will improve our ability to define molecularly the state of senescence and
will generate new fundamental knowledge about the onset of senescence. Our work could
improve the ability to predict tumor relapse after cancer therapy, help quantify a cell’s
physiological age and reproductive potential, identify ways to rejuvenate aged cells, and
improve the safety of senolytic drugs that eliminate senescent cells.

## Key facts

- **NIH application ID:** 10803979
- **Project number:** 1R01AG082942-01A1
- **Recipient organization:** UNIVERSITY OF COLORADO
- **Principal Investigator:** Sabrina Leigh Spencer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $349,636
- **Award type:** 1
- **Project period:** 2023-09-30 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10803979

## Citation

> US National Institutes of Health, RePORTER application 10803979, Progressive states of cell-cycle withdrawal (1R01AG082942-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10803979. Licensed CC0.

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