# SELECTING AND IDENTIFYING GENES IMPORTANT IN LONGEVITY

> **NIH NIH R01** · JACKSON LABORATORY · 1993 · $317,750

## Abstract

Mammalian aging may be too complex to show major changes as the result of
a single gene. Therefore this project will capture sets of genes that
increase longevity. Identifying these will lead to mechanisms causing
aging, and suggest means of retarding it. The mouse models used are
mammals similar to human beings, and should have similar mechanisms of
aging. Treatments retarding deleterious effects of aging would be of great
benefit to human health.

Selective breeding for increased longevity and increased reproductive life
span. Four sets of 4 way cross initial populations will be constructed
from 16 inbred strains showing maximum genetic diversity. This diversity
will maximize the availability of genes controlling aging. Selection for
long life will be conducted independently in each 4-way cross. Each
generation will be preserved as frozen embryos. Specific control lines
will be produced from specific crosses of Fl hybrids. After the rate of
increase in longevity with selection slows, the 4 different selected
populations can be intercrossed, and further selected for longevity to
test whether each population has unique genes with additive beneficial
effects that further increase life span.

For mice to live longer, all biological systems must function longer,
since the life span is limited by the first system to fail. Therefore
genes slowing age-related physiological and pathological changes in many
different biological systems should be captured. Genes retarding aging in
multiple systems are likely to lead to underlying mechanisms of aging.

Mapping longevity genes. DNA will be collected from all mice whose
longevity is measured, and a full battery of micro-satellite markers used
to locate chromosome regions that may be important in longevity. Candidate
genes will be suggested by information about these regions from the mouse
genome project Some candidates from old individuals will be identified in
3 years. However the likelihood of identifying important genes is greatly
enhanced by multigenerational comparisons, and by looking for regions in
which lines selectively bred for increased life spans consistently differ
from controls in all 4 selection experiments. This will be done when DNA
samples from selected and control populations are compared.

Testing mechanisms of aging. Genes related to longevity and to rates of
aging in different biological systems will suggest mechanisms. We will
compare rates of aging in different biological systems, testing
correlations with particular genes.

## Key facts

- **NIH application ID:** 3123543
- **Project number:** 1R01AG011643-01
- **Recipient organization:** JACKSON LABORATORY
- **SAM.gov UEI:** XR6LMXNKDJJ1
- **Principal Investigator:** DAVID E HARRISON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $317,750
- **Award type:** 1
- **Project period:** 1993-09-01 → 1998-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3123543

## Citation

> US National Institutes of Health, RePORTER application 3123543, SELECTING AND IDENTIFYING GENES IMPORTANT IN LONGEVITY (1R01AG011643-01). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3123543. Licensed CC0.

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