Changes in DNA methylation are tightly associated with the progress of ageing and ageing health in mammals including humans. This is the basis of Epigenetic Clocks. Unfortunately, nobody knows why… Furthermore, many other epigenetic marks and their associated writers and erasers have been implicated in longevity - the Sirtuin class of histone deacetylases (HDACs) are a good example.
Through our work on ageing and the environment we have linked loss of ageing health to an excess of acetyl coenzyme A, which is the limiting substrate for histone acetyl transferases (HATs). We predict that excess acetyl coenzyme A availability across life will disrupt histone acetylation patterns and drive the progressive degradation of other epigenetic patterns. Ageing of wild-type yeast is accompanied by massive dysregulation of the transcriptome, which is a likely consequence of increased histone acetylation, and we have previously shown that histone methylation is also progressively disrupted during ageing on glucose, coherent with progressive epigenetic changes.
Tri-methylation of histone H3 lysine 4 facilitates gene expression in ageing cells Cruz et al
Importantly, we find that interventions which promote ageing health, such as the galactose diet, prevent dysregulation of the transcriptome, linking maintenance of epigenetic and transcriptomic resilience to ageing health.
Dietary change without caloric restriction maintains a youthful profile in ageing yeast Horkai et al
This is an exciting area of science that we will be developing in the lab in coming years.
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