# AGING AND CIRCADIAN RHYTHMS IN THE TAU MUTANT HAMSTER

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 1993 · $156,358

## Abstract

The first (and only) single gene mutation in a mammalian circadian system
has recently been discovered in the golden hamster, this mutation alters
the period of the circadian clock (the endogenous period under free-
running conditions is reduced from the normal 24 hrs to about 20 hrs) and
the response of the clock to the phase shifting effects of light and
activity-inducing stimuli.  These effects on the circadian clock are
associated with ,.about a 50% decrease in the lifespan of the mutant
hamsters.  The overall objectives of the proposed studies are to
determine 1) if decreased longevity in tau mutant hamsters is due to
genetic or environmental factors, 2) if age-related changes in the
circadian clock system occur at an earlier age in tau mutant animals, 3)
what effect the tau mutation has on the timing of age-related changes in
the circadian clock system, and 4) if longevity is reduced in the tau
mutant animal because of the mutation's effects on the circadian clock
itself.

To reach these objectives, the circadian rhythm of locomotor activity
will be used as a marker rhythm for the state of the circadian clock
located in the suprachiasmatic nucleus (SCN) that underlies most
behavioral and physiological rhythms in mammals.  In one series of
experiments, male and female wild-type and tau mutant hamsters will be
exposed to either constant light (LL) or light-dark (LD) cycles in the
two circadian ranges (i.e. 20 or 24-hr LD cycles) to determine if the
decreased lifespan in the mutant animals is due to an intrinsic genetic
effect on longevity or to the inability of the circadian clock of mutant
animals to entrain normally to the standard 24-hr light cycle.  In a
second series of experiments, the effects of age on 1) the period of the
clock, 2) the phase relationship of the activity rhythm to entraining
light-dark cycles, 3) the rate of reentrainment following phase shifts in
the light-dark cycle, and 4) the response of the circadian clock to light
pulses or to a variety of activity-inducing stimuli will be determined in
wild-type and tau mutant hamsters.  The results of these studies will
establish whether a mutation in the circadian system has an effect on
normal age-related changes in the circadian clock system, as well as
whether such changes occur at an earlier age in the mutant hamsters that
corresponds in time with the decreased lifespan of the animals.  In a
third series of experiments, the effects of destruction of the circadian
clock in the SCN on longevity will be established in order to determine
if changes in the clock itself are responsible for the reduced lifespan
of the mutant animals.  A final series of experiments involving the
transplantation of fetal SCN tissue from both wild-type and mutant
hamsters to animals of the same or different genotype will be carried out
to determine the role of transplanted SCN tissue in the restoration of
circadian function in old hamsters.

In view of the central role played by the circadian clock ...

## Key facts

- **NIH application ID:** 3122841
- **Project number:** 5R01AG010870-02
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **SAM.gov UEI:** EXZVPWZBLUE8
- **Principal Investigator:** FRED W TUREK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $156,358
- **Award type:** 5
- **Project period:** 1992-09-30 → 1996-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3122841

## Citation

> US National Institutes of Health, RePORTER application 3122841, AGING AND CIRCADIAN RHYTHMS IN THE TAU MUTANT HAMSTER (5R01AG010870-02). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3122841. Licensed CC0.

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