The natural history of Huntington disease: possible role of "aging genes"

Abstract

In this paper we consider a model in which genetic factors that control aging also modify expression of the Huntington disease (HD) gene. Significant correlation coefficients were obtained for age-at-onset (AO) and age-at-death (AD) between affected parents and their affected offspring. However, more relevant to our hypothesis, the correlations between mean AD in normal sibs and AD in the affected parent (r = .57) and mean AD in their affected sibs (r = .54) are also significant. When onset is used instead of death for affected individuals the coefficients are .46 and .52, respectively. Also, AD in the normal parent is significantly correlated with AD in his affected (r = .39) and normal (r = .36) offspring. Current genetic theories on aging and related trends in HD are discussed. Our results and evidence from gerontological studies support the hypothesis that HD gene carriers with "superior" aging genes manifest symptoms later in life and have increased longevity over those with "inferior" aging genes.