# SENESCENCE AND LONGEVITY-MODULATING GENES

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA BERKELEY · 1993 · $252,422

## Abstract

Longevity, even in simple organisms, is undoubtedly regulated by multiple
genetic loci. We propose to identify and functionally characterize genes
that control one or more aspect of longevity in cultured human
fibroblasts, the yeast Saccharomyces cerevisiae, and genetically
heterogeneous and selectively bred mice.

Genes that modulate the finite proliferative lifespan of human fibroblasts
will be identified by a highly selective differential cloning strategy.
Candidate senescence-modulating human genes will be cloned and tested for
three functions: 1) inhibition of cell proliferation; 2) stimulation of
DNA synthesis or mitosis; and 3) because it is unlikely that any single
gene controls cellular senescence, cooperation with wild-type or mutant
viral oncogenes in stimulating DNA synthesis or mitosis.

In collaboration with Dr. Michal Jazwinski, S. cerevisiae will be used to
1) determine the effects of these genes on (yeast) longevity; 2) establish
whether they act as dominant or recessive alleles; 3) isolate yeast genes
that enhance or suppress their effects. In parallel, yeast genes shown by
Jazwinski's laboratory to affect longevity will be tested for function in
human fibroblasts. Yeast strains bearing or requiring viral oncogenes will
be used to isolate additional yeast and human genes that control longevity
or proliferative senescence.

In collaboration with Dr. Richard Miller, genes that modulate senescence
or longevity will be assessed for expression in young and old mice, either
genetically heterogeneous or selectively bred for late reproduction or
high or low immune function. mRNAs that are differentially expressed by
pure cell types isolated from young, old or selectively bred animals will
be identified, characterized for age- and tissue-specific expression, and
a subset will be cloned and tested for function in human fibroblasts and
S. cerevisiae.

The long range goal is to identify strong candidates for human longevity
assurance genes, and to know enough about their function to develop
rational strategies for testing in transgenic animals and, ultimately, for
therapeutic or interventional applications in humans.

## Key facts

- **NIH application ID:** 3123559
- **Project number:** 1R01AG011658-01
- **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:** 1993
- **Award amount:** $252,422
- **Award type:** 1
- **Project period:** 1993-09-06 → 1998-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3123559

## Citation

> US National Institutes of Health, RePORTER application 3123559, SENESCENCE AND LONGEVITY-MODULATING GENES (1R01AG011658-01). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3123559. Licensed CC0.

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