Common epigenetic pathways regulating ageing and circadian clocks: implications for therapeutic intervention

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One important feature of getting old is deteriorated sleep quality. Sleep is regulated by circadian clocks, the internal time pieces in various body organs, consisting of clock genes and proteins that are capable of generating ~24 hr rhythmic outputs. Age-associated sleep disorders are thought to be due to loss of proper circadian regulation, such as reduced amplitude, non-24 hour periodicity or inappropriate phase. Studying changes in circadian clocks with ageing will in the long run aid therapeutic drug design targeting sleep disorders in the elderly.Expression and stability of the clock genes and proteins are controlled by modifications such as acetylation/deacetylation, describing the presence or absence of the acetyl group on target proteins. Many of these modification mechanisms have been found as hallmarks for ageing. I will investigate changes of rhythms and acetylation/deacetylation activities with ageing process using animal models and skin cells isolated from biopsies of human subjects. Changes of modifications will be correlated with alterations in circadian rhythms. By filling in questionnaire, the chronotype and sleep pattern will be correlated to the rhythms in skin cells. I will also probe the possibility of altering the acetylation/deacetylation balance by drugs in order to restore the age-related rhythm changes.