Aging and the sex-specific chromatin in Drosophila The chromatin landscape is key for gene regulation, but little is known about how it differs between sexes, or over adult life. There is accumulating evidence that chromatin changes during an individual's lifespan contribute to cellular aging. In particular, loss of heterochromatin has been observed in aged cells of several species, including Drosophila. Age-specific mortality rates of male flies are higher and average lifespans are shorter than those of females. Males also contain substantially more heterochromatic DNA than females, due to the presence of a large, repeat-rich Y chromosome, and our preliminary data suggest that the presence of sex chromosomes with different epigenetic profiles in Drosophila (that is, a hyper-transcribed dosage compensated X chromosome, and a silenced heterochromatic Y) result in global changes of chromatin structure between sexes. We propose to compare sex-specific gene expression and epigenetic profiles in Drosophila species and strains with different sex chromosome karyotypes across their lifespan, to study the influence of sex- specific chromatin differences on cellular aging. We will experimentally modify protein levels of genes involved in heterochromatin maintenance, to directly test if heterochromatin formation is a main contributor to sex-specific epigenetic profiles and longevity. Additionally, we will assay chromatin states in time- series samples, and characterize tissue-specific chromatin states in aged vs. young flies, to address the temporal dynamics of changes in chromatin during aging, and potentially important differences in cellular aging across tissues.
Aging is characterized by a progressive decline in vitality and tissue function, and studies of diverse species have revealed that chromatin undergoes extensive rearrangement during aging, and the stochastic or chronic deterioration of chromatin organization during the lifespan of an individual may contribute to cellular aging. Age-related disorders, such as cardiovascular diseases, stroke, diabetes and cancer have become the leading causes of death in developed countries, and their relative importance differs between males and females. We will study chromatin modifications throughout the lifespan of male and female Drosophila, to establish the role of chromatin as a modulator of sex-specific aging.
