June 24: Members of H3K4 Trimethylation Complex Regulate Lifespan in a Germline-Dependent Manner in C. elegans
Category: General
The longevity and the plasticity of aging appears to be controlled by epigenetic modification of chromatin. It also has been suggested that aging is associated with depletion and deterioration of the stem cell compartment within various tissues and organs of the body. In the June 16th online edition of Nature, scientists from Stanford University, E. L. Green et al., published their study on the relationship between histone methylation and longevity in round worms (C. elegans). The researchers noted that histone methylation is critically important in maintaining stem cell pluripotency in mammals, but not much is known regarding the mechanisms of methylation and aging. From their experimental results, the investigators identified ASH-2 tithorax complex as a key regulator of lifespan in C. elegans due to trimethylation of histone H3 at lysine 4 (H3K4). Additionally, the results revealed that deficiencies in members of the ASH-2 complex (either ASH-2, WDR-5, or methyltranferase SET-2) extended worm lifespan. It was also shown that H3K4 demethylase RBR-2 is required for normal lifespan, which supports the thesis that "excess H3K4 trimethylation is detrimental for longevity." Life extension by ASH-2 complex deficiencies also required an intact adult germline and the continuous production of mature eggs. The authors concluded from their experimental data that "ASH-2 and RBR-2 act in their germline, at least in part, to regulate lifespan and to control as sent of genes involved in lifespan determination." (It may also suggest that these complexes may also modulate the stem cell compartments in the worm?).











