# CELLULAR SENESCENCE AND CONTROL OF GENE EXPRESSION

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA BERKELEY · 1991 · $214,673

## Abstract

Normal human fibroblasts invariably undergo cellular senescence, whereby
they irreversibly cease proliferation after a finite number of population
doublings in culture.  This number is inversely proportional to the age of
the donor.  Senescence in culture may be a manifestation, at the cellular
level, of aging in vivo.  It may also constitute an important mechanisms
for surtailing tumorigenic progression.  It is well-established that
senescent human fibroblasts express one or more dominant inhibitor of cell
proliferation.  However, the nature of the irreversible growth arrest shown
by senescent cells remains poorly understood.

Recently, we identified several specific changes in gene expression that
occur when human fibroblasts senesce.  Senescent cells:  1) underexpress
the mRNA for a non-cell cycle regulated gene of unknown function (pHE-7);
2) express a unique, polyadenylated histone variant mRNA; 3) show normal
serum-dependent induction of two protoncogene mRNAs and ornithine
decarboxylase (odc) mRNA, but are deficient in odc enzyme activity; 4)
acquire a specific, transcriptional block that prevents the serum-dependent
induction of the c-fos protooncogene.

We propose to explore the mechanisms by which these changes in gene
expression occur and to study their impact on cell proliferation.
Specifically, we plan to:  1) clone and characterize the pHE-7 gene,
examine the basis for its underexpression in senescent cells, and determine
the effect of elevated expression on proliferation and senescence; 2) clone
and characterize the histone variant expressed by senescent cells and
identify factors that may be important in regulating expression in
senescent cells; 3) continue our study of serum-inducible mRNAs, exploring
the possibility that the expression of yet other genes may be altered at a
transcriptional or posttranscriptional level in senescent cells; 4)
identify factors that associate with regulatory regions in the c-fos gene
and determine the impact of elevated fos expression on proliferation and
senescence.

These studies will provide a framework in which to begin to understand the
molecular basis for cellular senescence and the irreversible block to cell
proliferation.

## Key facts

- **NIH application ID:** 3121851
- **Project number:** 5R01AG009909-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **SAM.gov UEI:** GS3YEVSS12N6
- **Principal Investigator:** Judith Campisi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $214,673
- **Award type:** 5
- **Project period:** 1990-09-01 → 1995-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3121851

## Citation

> US National Institutes of Health, RePORTER application 3121851, CELLULAR SENESCENCE AND CONTROL OF GENE EXPRESSION (5R01AG009909-02). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3121851. Licensed CC0.

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