High throughput yeast replicative lifespan screen uncovers histone deacetylase complex HDA as novel regulator of aging

Budding yeast Saccharomyces cerevisiae is a powerful model organism in the field of aging research, previous studies on budding yeast have revealed many conserved aging regulators. However, the traditional replicative lifespan assays are labor-intensive and low-throughput, limiting its potential as a broad genetic screening platform for research on aging. In this study, we developed a new Sequencing based yeast replicative lifespan screen (SEBYL) method, and utilized it to identify regulators of RLS from Yeast Knock-out (YKO) collection. The SEBYL method was able to generate lifespan data that concord with classical experiments. From SEBYL results we discovered that mutation in HDA, a class II histone deacetylase complex, robustly extend RLS. Further study reveals that deletion of HDA components activates the transcription of trehalose metabolism pathway, protecting cells from various sources of stress, thus extending lifespan.