# GENETIC CONTROL OF LONGEVITY IN MICE

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 1993 · $277,160

## Abstract

This project has two principal goals: (1) to identify regions of the mouse
genome that encode genes that contribute significantly to longevity; and
(2) to use selective breeding strategies to produce strains of mice that
age at different rates. The experiments will utilize genetically
heterogeneous mice bred by a four-way Cross between (C57BL/6 x SJL)F1
females and (AKR x DBA/2)F1 males ("HET" mice). The analytical genetic
study will begin by typing 200 HET mice at each of 190 informative loci,
using PCR-based amplification of primer pairs that discriminate among 2 or
more of the grandparental inbred strains. A second cohort of 200 HET mice
will then be genotyped using the original battery of primer pairs plus a
second set of 95 probes selected to provide higher resolution in regions
suggested to be of particular interest during the initial screen. Mice in
the second cohort will also be tested at 6 and 18 months of age for
indices of age-related immune decline: the proportion of memory T cells
within the CD4 helper and CD8 killer T cell subsets. Each of the HET mice
will be sacrificed when moribund to obtain longevity and pathology data.
An interval-based mapping strategy will then identify quantitative trait
loci (QTL) that influence longevity. Parallel analyses will establish
whether these, or other QTL, also influence the incident rates of major
disease processes, or influence the rate of physiological aging as
measured by shifts in T lymphocyte subset composition. The selective
breeding study will generate lines of mice, starting from HET stock, based
on differences in (a) early life hemagglutinin response; or (b)
distribution of reproductive effort. These selective criteria have been
chosen because each can be assayed within the first 8 months of life, and
because theoretical and experimental considerations suggest that each
trait may be influenced by genes that pleiotropically affect aging rate
and hence longevity. The selection protocols incorporate independent
replication (bidirectional for the hemagglutinin protocol) and parallel
development of unselected control stocks for genetic and phenotypic
comparison to the selected lines. When breeding has produced lines of mice
that differ in the selected criteria, groups of animals from each selected
line will be set aside for determination of longevity, pathologic study,
and genotyping using primer sets developed by analysis of the HBT stock.
RNA from old and young HET mice, and later from selectively bred animals,
will be provided to Dr. Judith Campisi for a collaborative study of age-
related alterations in gene expression in monotypic cell preparations.
Long-term goals include (a) selection of mice based on genotype at QTL
identified through analysis of HET mice; (b)positional cloning of genes
within regions identified by QTL analysis of HET and selected mice; and
(c) detailed physiological analysis of proposed anti-aging defenses in
mice of short- and long-lived genotypes.

## Key facts

- **NIH application ID:** 3123573
- **Project number:** 1R01AG011687-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **SAM.gov UEI:** GNJ7BBP73WE9
- **Principal Investigator:** RICHARD A MILLER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $277,160
- **Award type:** 1
- **Project period:** 1993-09-01 → 1998-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3123573

## Citation

> US National Institutes of Health, RePORTER application 3123573, GENETIC CONTROL OF LONGEVITY IN MICE (1R01AG011687-01). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3123573. Licensed CC0.

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