Liam C Hunt | Position effect variegation (PEV) as an epigenetic aging clock: visualization..

Liam C Hunt Biology Department, Rhodes College, USA ARC-2026 | INNOVINC Title: Position effect variegation (PEV) as an epigenetic aging clock: visualization of age-dependent loss of heterochromatin and longevity associated with enhanced heterochromatin Abstract: Epigenetic alterations such as DNA methylation and histone modifications can accumulate as a result of cellular aging. In some cases, epigenetic alterations may cause visible changes in phenotype that could be used as a biomarker. Position Effect Variegation (PEV) is one example in Drosophila Melanogaster where the white gene is moved to a chromosomal position subject to heterochromatin mediated silencing resulting in mosaic red and white eye color that can be modified based on the degree of heterochromatin formation. We show that in several chromosomal locations PEV phenotypes are modified by aging and indicate a loss of heterochromatin mediated silencing in old age1. This epigenetic loss of heterochromatin is progressive with age and coincides with increased transcription of centromeric genes1. Furthermore, genetic and environmental interventions that promote heterochromatin formation, due to enhanced variegation phenotypes, are shown to extend lifespan1. Recent unpublished research has used selective breeding to isolate populations enriched for enhanced and suppressed variegation phenotypes, corresponding to enhanced and suppressed heterochromatin formation. One of these enhanced heterochromatin populations, ENH, has longer lifespan than controls and we are able to attribute this to a heterozygous genetic variation that is dominant for PEV phenotype effects and recessive for viability. Genetic complementation studies indicate the ENH variant is due to loss of function mutation in the second chromosome around the cytogenetic band 47B. While we are narrowing down the gene responsible we have tested epistasis with suppressor of variegation mutants and find that the enhanced variegation and heterochromatin phenotype is insufficient to promote longevity by itself. Altogether this suggests that loss of heterochromatin may be a sign of aging but is not causative for aging. Although longevity promoting genetic mutations may enhance heterochromatin this is likely a result of molecular changes within cells that also coincide with reduced aging and are not always strictly necessary for longevity. 1. Tedeschi, S. et al. Position effect variegation (PEV) as an aging clock: visualization of age-dependent loss of heterochromatin and longevity associated with enhanced heterochromatin. Sci. Rep. 16, 4655 (2026). #geriatrics #agingresearch #aging #agingresearch #aging #Aging2026 #agingconference #agingmeetings #geriatrics #geriatricsconference #geriatricsmeeting #Innovinc #innovincconferences #Aging2026inPrague #ARC2026 #AgingResearch #Rejuvenation #Longevity #HealthyAging #RegenerativeMedicine #StemCells #CellularSenescence #AntiAging #Geroscience #Biotechnology #MedicalConference #LifeSciences #Prague