Dena Dubal - MD, PhD
AFAR Research Grants for Junior Faculty - 2015
Assistant Professor - University of California, San Francisco
Epigenetics of the X-Chromosome and Aging
Females exhibit a longer lifespan than males across most of the animal kingdom. But how and why females live longer in normal aging and show less vulnerability to certain age-related brain diseases remains unknown.
Dr. Dubal's group recently discovered that sex chromosomes—specifically the X chromosome—impact female longevity and susceptibility to disease. Equal dosage of X in both sexes is ensured by X chromosome inactivation (XCI), a random transcriptional silencing of one X in the cells of female mammals. So if males and females both have one X chromosome due to XCI in females, how does the X confer an advantage in females?
Indeed, the inactive X is not completely silenced in females. Dr. Dubal's preliminary data reveal the presence of escape from XCI in neurons following age- and disease-related toxicity. This epigenetic (caused by modification of gene expression rather than alteration of the genetic code) change in the status of the X chromosome could lead to increased X–linked function in females. Thus, Dr. Dubal's team hypothesizes that escape from XCI occurs in the aging and diseased female brain, and that this epigenetic alteration promotes resilience.
Dr. Dubal's group will further study the escape from XCI using novel genetic and epigenetic approaches in brain aging and disease. The group hopes to determine the functional relevance of epigenetic escape from XCI to aging and whether it confers resilience. Understanding epigenetic alteration of the X chromosome in aging may help to optimize aging and mitigate age-related vulnerabilities in both men and women.
View all grantees for AFAR Research Grants for Junior Faculty in 2015