Cologne Seminars on Ageing "mTOR drives daily physiology"

About John' s talk:

The genetic circuits that facilitate circadian transcriptional regulation have been successfully delineated over the last three decades, however, the mechanisms that drive daily regulation of mammalian physiology are quite poorly understood. We have explored the hypothesis that mechanistic target-of-rapamycin (mTOR) regulates the temporal coordination of cellular and
organismal physiology. We show that mTOR activity is a major input to, and mediates many outputs from, the cellular clockwork. In cultured cells, mTOR inhibition abolishes circadian output rhythms with only modest effects on clock protein oscillations. We also report similar findings in Neurospora crassa (fungus) and Arabidposis thaliana (plant), suggestive of an
evolutionarily conserved role for mTOR that is consistent with its essential function in eukaryotes. In mice, mTOR inhibition severely attenuates daily variation in most physiological processes, whilst clock protein and locomotor activity rhythms remain intact. Moreover, across multiple mouse tissues, most daily rhythms of protein abundance and phosphorylation found in young mice are abolished by mTOR inhibition, and increased in aged mice. We conclude most daily physiological rhythms depend on mTOR activity, and can be uncoupled from cellular and central timekeeping.