# FIBROBLAST AGING AND PROGRAMMED CELL DEATH

> **NIH NIH R01** · MCGILL UNIVERSITY · 1991 · $64,690

## Abstract

What remains one of the most fascinating areas in biological research is
the mechanism regulating the events of aging.  The main theme of this
proposal suggests that a defined genetic program is in control of the
irreversible termination of cell replication as cells become senescent.  We
have hypothesized that normal fibroblasts are destined for senescent
nonproliferation as the initial part of a final program leading to death.
Therefore senescence similar to terminal differentiation, may be a state,
obligatory and dominant in every cell, and distinctly different from the
transient growth-arrest seen in quiescence.  Here we hypothesize that a
specific program of gene expression sis activated for cells to become
nonproliferative and senescent.  The first step of our research along this
line is to identify gene(s) or their product(s) uniquely present in
senescent cells and absent in their young growing or nongrowing
counterparts.  We have succeeded in identifying a first example of such a
gene product, terminin.  Identification of terminin provides a handle to
test our hypothesis by performing experiments to:  (1) characterize
terminin presence in tissues by immunohistochemical studies; (2) assess
terminin expression qualitatively and quantitatively in tissues derived
from young, middle-aged, and old animals; (3) characterize the cellular
identity of terminin-positive granules by immunogold ultrastructural
studies and histochemical enzymatic assays; (4) characterize possible
biochemical mechanisms regulating terminin expression; (5) purify terminin
polypeptides, sequence the protein and generate macromolecular probes; and
(6) carry out initial cloning and sequencing of cDNA clones encoding for
terminin proteins.  Results of these experiments will provide us the
necessary information and tools to investigate the next series of questions
on how terminin gene expression is controlled and what is the function of
the protein relating to the aging process.  Ultimately, it will shed light
on the mechanism of how cells turn off replication permanently as seen in
fibroblasts senescence or terminal differentiation, the last part of a long
physiological process preparing for the final event of apoptosis, the
destiny of every cell.

## Key facts

- **NIH application ID:** 3121095
- **Project number:** 5R01AG009278-02
- **Recipient organization:** MCGILL UNIVERSITY
- **SAM.gov UEI:** VJ62F6V2LE48
- **Principal Investigator:** EUGENIA WANG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $64,690
- **Award type:** 5
- **Project period:** 1990-09-01 → 1993-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3121095

## Citation

> US National Institutes of Health, RePORTER application 3121095, FIBROBLAST AGING AND PROGRAMMED CELL DEATH (5R01AG009278-02). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3121095. Licensed CC0.

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