New Pathway Links Epigenetics And Aging Was Found

It has been widely acknowledged for nearly ten years that epigenetic marks change as cells
age. For instance, Sir2, which is implicated in the association between calorie restriction and
lifespan, is known to affect metabolic pathways and alter the acetyl marks on histones. While,
in the latest study, scientists have found another pathways that links epigenetic and agingH3K36 methylation and it decreases as yeast and worm cells age.
This finding provides further support for the idea that as cells age, you are inclined to get
more open and permissive chromatin. commented Shelley Berger, senior author of this
paper.
Along with post-doctoral fellow Payel Sen, Berger carried out a high-throughput screen for
histone mutations that affect the lifespan of Saccharomyces cervisiae. Among the relevant

mutations was one in histone 3 (H3). The study showed that when the K36 residue was mutated
to something that cant be methylated, the lifespan would be shortened. said Sen. And on the
other side, the team knocked out the demethylase that acts on H3K36, forcing the histone to stay
methylated and the yeast cells survived longer.
Previously, researches have shown that the modification of this histone will affects the production
of cryptic transcripts, short bits of RNA which functions are unknown. With high-resolution RNAseq adopted, this very team investigated into the role of cryptic transcripts. Levels of these short
rogue transcripts remained low in younger cells or those lacking the demethylase. However, when
they become older, control cells lost methylation of H3K36 and the levels of the transcripts
increased. Furthermore, the same results got when tested in worms.
What we havent published is that this pathway might work in human cells. noted Berger.
H3K36 might not be the exact histone that regulates cryptic transcripts and mediates aging in
humans, Berger suspects there must exist a similar pathway that plays the same role.
If this cryptic regulation goes on in human cells, further steps is to design an inhibitor that stops
the production of the cryptic transcripts. This, however, could help reverse or prevent the bodywide effects of aging cells.