Splenic lymphocytes from young, 15 month old and 24-28 month old C57BL/6 mice housed in a constant environment were studied. Single cell suspensions were cultured in vitro with T cell mitogens, phytohaemagglutinin and Concanavalin A, and the B cell mitogen, lipopolysaccharide. Functional capacity of the T and B lymphocytes was assessed by the mitogen-induced incorporation of tritiated thymidine by dividing cells. Circannual rhythmicity in levels of in vitro activation of T and B lymphocytes was expressed by cells from mice of all ages; however, the properties of the rhythms were modified in cells from older mice. Phases of elevated responses alternated with phases of depressed responses; the freerunning periods of these rhythms increased from approximately 12 to 15 months in the two older groups of mice. Greatly extended phases of depressed responses, from 1 to 8 months, were characteristic of the rhythms of older animals and, consequently, extended the time of possible increased susceptibility to environmental assaults. Amplitudes of both T and B lymphocyte rhythms were unchanged in young and adult mice, but the T-cell rhythms were damped in senescent animals. This change in the relationships of T to B cell activation rhythms is another example of imbalance in the immune system with age. The age-realted changes in expressed circannual rhythms by a population of mice suggest genetic control and parallel changes in gene expression over the lifespan. Since freerunning periods of the circannual rhythms increased with age, they were out of phase with those of young mice. The resulting continuously changing phase relationships periodically obscured the expected age-related decline in lymphocyte activation. This explains discrepancies in data reported by others showing no change in, increased or decreased lymphocyte activation with age. The significance of these results is that they show decay of temporal organization of circannual rhythms with age which may be associated with the physiological deterioration of organisms.
