Position effect variegation (PEV) as an aging clock: visualization of age-dependent loss of heterochromatin and longevity associated with enhanced heterochromatin.

Abstract

The heterochromatin loss model of aging suggests there is an age-dependent reduction in epigenetic factors that form and maintain the heterochromatin state of chromosomes. Position Effect Variegation (PEV) can visually report phenotypes of heterochromatin mediated silencing in Drosophila Melanogaster eyes and we use PEV to examine the association between heterochromatin state changes and aging. Pericentric inserts causing PEV showed suppressed variegation phenotypes in old age compared to young age and were confirmed to be associated with progressively increasing transcription, indicating loss of heterochromatin mediated silencing. Within a single population, animals with enhanced PEV phenotypes live longer than those with more suppressed PEV phenotypes, suggesting that small differences in environmental or genetic factors within this population could be responsible for differences in heterochromatin and lifespan. Environmental factors could enhance heterochromatin, reduced nutrient diet and lower temperature coincided with enhanced heterochromatin and longer life. Furthermore, genetic variants associated with long life, including chico mutants, lead to increased heterochromatin and enhanced PEV phenotypes. Therefore, aging can be linked to heterochromatin loss and developmental increases in heterochromatin are associated with longevity. Thus, PEV reporters act as aging clocks demonstrating loss of heterochromatin that progresses with age and epigenetic alterations that can promote longevity.