# YEAST--A SOURCE AND A TEST SYSTEM FOR MAMMALIAN LAGS

> **NIH NIH R01** · LSU HEALTH SCIENCES CENTER · 1993 · $268,049

## Abstract

During the past decade, convincing evidence has accumulated in several
invertebrate systems demonstrating that longevity is a genetically
determined trait. This evidence has bolstered the conviction that aging
possesses a genetic determinant in vertebrates as well.  Longevity is
clearly a polygenic trait. The objectives of the proposed research are
two-fold. First, we wish to develop and to implement a relatively simple
system for the evaluation of candidate longevity-assurance genes (LAGs),
genes that play a role in determining longevity. The experimental system
we will utilize is the yeast Saccharomyces cerevisiae.  Second, we plan to
determine whether the yeast longevity-assurance gene LAG1 is involved in
determining life span or maintaining "youthful" function in mammals, as a
model for the analysis of other yeast LAGs in higher eukaryotes.
Specifically: a) A functional cloning approach will be adapted to isolate
yeast homologs of the SV4O T-antigen and then of candidate nematode and
fruit fly LAGs. These genes will be directly tested for LAG function in
yeast; b) The human cDNA homologous to yeast LAG1 will be cloned and
characterized. This aim will include an examination of the level of
expression of the human gene in a variety of human cell types and tissues.
It will also involve an analysis of expression during the replicative life
span of human diploid fibroblasts in tissue culture and in fibroblasts
from human donors of different ages; c) The effects on the replicative
life span of fibroblasts in culture of overexpressing human LAG1 and of
eliminating its expression will be examined; d) The mouse cDNA homolog of
LAG1 will be cloned and characterized. The expression of the gene in the
mouse will be ascertained at various stages of development and during the
adult life span by in situ hybridization. This analysis will form the
prelude to the final specific aim; e) Transgenic mice overexpressing LAG1,
as well as mice expressing dominant-negative mutations of LAG1, will be
generated. The effects of these genetic alterations on the development,
aging, and life span of the animal will be determined. The overall goal of
the proposed studies is to pave a two-way street in which yeast LAGs can
be tested in mammals and candidate LAGs from other eukaryotes can be
tested rapidly in yeast. This research should provide insights into the
basic biological processes of aging and thus to contribute to the quality
of the later years of life in humans.

## Key facts

- **NIH application ID:** 3123561
- **Project number:** 1R01AG011660-01
- **Recipient organization:** LSU HEALTH SCIENCES CENTER
- **SAM.gov UEI:** M7KCJ79FAVH5
- **Principal Investigator:** S MICHAL JAZWINSKI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $268,049
- **Award type:** 1
- **Project period:** 1993-09-06 → 1998-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3123561

## Citation

> US National Institutes of Health, RePORTER application 3123561, YEAST--A SOURCE AND A TEST SYSTEM FOR MAMMALIAN LAGS (1R01AG011660-01). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3123561. Licensed CC0.

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