Expression profiles of PERIOD1, 2, and 3 in peripheral blood mononuclear cells from older subjects

Aims: Circadian clocks regulate daily rhythms of behavior and physiology such as the sleep-wake cycle and hormonal secretion. Numerous characteristics of the behavioral and physiological processes change with age. In this study, we evaluated the circadian clockwork in older people by measuring daily profiles of PERIOD (PER) gene expression in peripheral blood mononuclear cells (PBMCs). Main methods: Blood samples were collected from 6 healthy older subjects (mean age 62 years) at 2-h intervals over a 24-h period under a semi-constant routine condition where masking effects are minimized. PBMCs were isolated from whole blood and temporal mRNA expression profiles of PER1, PER2, and PER3 were determined by RT-PCR. Phases of the PER rhythms, and times of sleep onset and offset were determined using data from those subjects who showed significant 24-h rhythms. The values for the parameters were compared between the older subjects and 8 young control subjects (mean age 21 years). Key findings: Prominent daily rhythms of PER1, PER2, and PER3 mRNA levels, advanced sleep-wake timing and advanced phases of PER rhythms were observed in the older subjects compared to the young controls. There was no significant age-related phase difference in PER1 or PER2 rhythm with respect to sleep timing; however, PER3 expression pattern was altered in the older subjects. Significance: This preliminary study shows that human circadian clockwork in PBMCs remains intact at least until the presenile stage and suggests that the altered PER3 expression pattern may reflect decreased homeostatic sleep drive in older people.