# HUNTINGTON DISEASE: A NEUROLOGICAL MARKER OF AGING

> **NIH NIH R01** · INDIANA UNIVERSITY INDIANAPOLIS · 1991 · $268,308

## Abstract

Huntington disease (HD) is an autosomal dominant disease
characterized by premature central nervous system degeneration,
primarily in the striatum of medium-sized spiney neurons.  HD has
a relentless 15-20 year course from onset to death.  Age of symptom
onset is highly heritable, ranging from ages 3 to 70.  Animal
models led to the hypothesis that "poor aging genes" result in
early HD onset.  A test of this hypothesis in 214 families revealed
correlations of about 0.5 (P less than 0.001) between HD age of
onset and age of death of unaffected first degree relatives but
insignificant correlations between age of onset in affected
individuals and longevity of their spouses, supporting the "aging
gene" hypothesis and making HD age of onset a more powerful
predictor of mortality than many currently used biomarkers of
aging.

Children of mothers with HD have onset of symptoms an average of
3.5 years later than the children of affected fathers, providing
a testable hypothesis of a maternal effect that delays neuronal
death with aging.

We propose a genetic-epidemiological study of adults, who had a
parent with HD, to determine which biomarkers of aging, diseases
of aging or disease risk factors are related to familial age of
onset in HD.  This study will further test the hypothesis that HD
is a stressor of central nervous system aging, provide insight into
the maternal influence that delays the symptoms of neuronal death
and measure the effects of neuronal death on biomarkers of aging
in the subjects who later have symptoms.

Similar hypotheses have been proposed to explain onset of
Alzheimer's and Parkinson's diseases.  We judge HD especially
appropriate to test this family of the brain and well documented
families are available from the National HD Research Roster.  The
fact that the HD gene has been located on the tip of the short arm
of chromosome 4 will undoubtedly lead to understanding of its
molecular pathology and ease the translation of findings to the
understanding of other causes of premature neuronal death.

## Key facts

- **NIH application ID:** 3120698
- **Project number:** 5R01AG008918-03
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **SAM.gov UEI:** SHHBRBAPSM35
- **Principal Investigator:** Joe C Christian
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $268,308
- **Award type:** 5
- **Project period:** 1989-07-01 → 1994-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3120698

## Citation

> US National Institutes of Health, RePORTER application 3120698, HUNTINGTON DISEASE: A NEUROLOGICAL MARKER OF AGING (5R01AG008918-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3120698. Licensed CC0.

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