# STRESS, REPAIR, AND AGING

> **NIH NIH R01** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 1990 · $229,758

## Abstract

The objectives of the research described in this proposal are to generate a
variety of stress-resistant mutants in the yeast S. cerevisiae and in the
nematode C. elegans, with an emphasis on mutants resistant to oxidative
stress.  Detailed biochemical and genetic characterization of these mutants
will be followed by their use to address the mechanisms of aging of a
multicellular organism such as C. elegans and of the mother cells of a
unicellular organism such as S. cerevisiae.  In particular, we shall test,
using a generally applicable approach, a hypothesis according to which the
species-specific life spans of iteroparous organisms are an indirect
consequence of optimization rather than maximization of the repair/defense
systems of a species in the course of its evolution.

Specific Aims

1) Isolation and analysis of yeast (S. cerevisiae) mutants hyperresistant
to an acute (short-term) exposure to hydrogen peroxide.     2)
Determination of mother cell life spans and generation times in the
hyperresistant mutants, and comparison with life spans of mother cells in
congenic wild-type strains.

3) Isolation, using a turbidostat, and analysis of S. cerevisiae mutants
hyperresistant to a chronic (continuous) exposure to either hydrogen
peroxide or buthionine sulfoximine, an
inhibitor of glutathione biosynthesis.          4) Direct selection for S.
cerevisiae strains with an increased mother cell longevity by repeated
enrichments for older mothers, using a cell sorter-based experimental
approach.
       5) Isolation and analysis of nematode (C. elegans) mutants
hyperresistant to an acute exposure to hydrogen peroxide.
       6) Isolation, using a modified chemostat technique, and analysis of
C. elegans mutants hyperresistant to a chronic exposure to either hydrogen
peroxide or buthionine sulfoximine.    Examination of life spans of the
above C. elegans mutants and parental strains.

Detailed mechanistic and functional understanding of the stress response
systems, in particular of those that underlie the resistance to oxidative
stress, is expected to illuminate a number of biological problems, and
especially the problem of aging.

## Key facts

- **NIH application ID:** 3120794
- **Project number:** 1R01AG008991-01
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **SAM.gov UEI:** E2NYLCDML6V1
- **Principal Investigator:** ALEXANDER J VARSHAVSKY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $229,758
- **Award type:** 1
- **Project period:** 1990-05-01 → 1995-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3120794

## Citation

> US National Institutes of Health, RePORTER application 3120794, STRESS, REPAIR, AND AGING (1R01AG008991-01). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3120794. Licensed CC0.

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