# SENESCENT CELL DERIVED INHIBITORS OF DNA SYNTHESIS

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 1993 · $236,193

## Abstract

The limited proliferative potential (cellular senescence) of normal human
cells in culture has provided an important model for the study of aging
at the cellular level.  The model has been validated by various data,
including the fact that cells from individuals that exhibit premature
aging have lower division capability.  Evidence that genetic events
rather than random damage results in senescence has come from somatic
cell hybridization studies which have shown that the senescent phenotype
is dominant in hybrids between young and senescent, as well as normal and
immortal human cells.  In addition, convincing evidence has been obtained
to indicate that senescent cells express a surface membrane associated
protein inhibitor of initiation of DNA synthesis that is not present in
young cells.  We hypothesized that expression of this inhibitor is the
endpoint of the genetic events resulting in senescence.  We have
demonstrated by microinjection that DNA synthesis inhibitory mRNA is
highly abundant in senescent but not young cells, suggesting the
feasibility of cloning the cDNA encoding the inhibitor.  We have recently
cloned three cDNAs derived from senescent cells by an expression
screening approach.  These are called sdi or senescent cell derived
inhibitors.  One clone is expressed at approximately 10 fold higher
levels in senescent and quiescent cells compared to cycling young cells.
Quiescent cells have been shown to express a protein inhibitor of DNA
synthesis with some, but not all, properties of that produced by
senescent cells. sdi1 is therefore a good candidate for the gene encoding
the protein inhibitor(s) of DNA synthesis.  Alternatively, sdi1 could be
coding for an inhibitor of DNA synthesis that has not been previously
identified as the cDNA sequence has no significant homology to sequences
present in GenBank and the EMBL databases.  The goals of this proposal
are to elucidate the mechanisms of action of sdi1 and to determine its
role during in vitro and in vivo aging.

## Key facts

- **NIH application ID:** 3123057
- **Project number:** 5R01AG011066-02
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **SAM.gov UEI:** FXKMA43NTV21
- **Principal Investigator:** JAMES SMITH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $236,193
- **Award type:** 5
- **Project period:** 1992-09-30 → 1995-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3123057

## Citation

> US National Institutes of Health, RePORTER application 3123057, SENESCENT CELL DERIVED INHIBITORS OF DNA SYNTHESIS (5R01AG011066-02). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3123057. Licensed CC0.

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