ChIP sequencing of H3K27ac mark of C.elegans treat with las1l /Y6B3B.9 RNAi

Aging has been defined as a progressive decline in physiological function over time. This study identifies genes associated with the aging process that are present in nematodes, killifish, zebrafish, and mice in an evolutionary conserved manner. Out of 45 genes identified in our comparative approach, we find that impairing the las1l/Y6B3B.9 gene, which encodes for a ribosomal biogenesis factor, results in the most pronounced extension of Caenorhabditis elegans lifespan. Impairment of las1l/Y6B3B.9 reduces 60S ribosomes subunit expression and impairs protein synthesis. In addition, we discover a novel role of las1l/Y6B3B.9 in regulating histone marks and transcription, revealing responsibility of the tyrosine phosphatase Y39A3A.4 and its target, NUCL-1, for las1l/Y6B3B.9- mediated lifespan extension, providing pharmacological targets for fine-tuning of the translational machinery in higher organisms, to ultimately promote healthspan.