035. Circadian rhythms and the early life programming of adult physiological systems

Abstract

We are all familiar with the idea that the external environment influences many diverse physiological systems. For example, the level of nutrition can not only influence adult health directly, but also fetal development and subsequently many adult functions in the offspring. Maternal stress can affect fetal outcomes as can the administration of drugs during pregnancy. Until recently, however, the daily changes in environmental light have been considered to really only influence the time that we sleep and in many other species the optimal time to mate. The impact of circadian rhythms on life trajectory has had little attention.

In the last 5 years it has become clear that circadian rhythmicity is entrenched in virtually every cell of our bodies. A suite of clock gene transcription factors that include Clock, Bmal1 and the period and cryptochrome genes, generate a robust daily cycle of transcription and translation of hundreds of proteins. This cellular clock system is synchronised with the external photoperiod through retinal light perception, the hypothalamic suprachiasmatic nucleus (SCN) and neural and hormonal pathways. Most importantly when the clock system in peripheral tissues is disrupted, a growing list of detrimental consequences are being uncovered. As an example, mice with mutations in either Clock or Bmal1 have non-rhythmic peripheral tissues and exhibit mild to severe reproductive failure and metabolic dysfunction. Null per2 mice have a higher incidence of salivary gland hyperplasia, teratomas and increased susceptibility to radiation induced lymphomas. It is also apparent that intrauterine insults (e.g. cocaine administration, poor nutrition and stress) can have long term effects on the central circadian timing system in the SCN. Whether this involves alterations in neural development or gene function is not known. Nevertheless it is time we paid more attention to the temporal nature of our environment as a possible contributor to lifetime disorders and diseases.