EFFECTS OF AGING ON THE CIRCADIAN-RHYTHM OF WHEEL-RUNNING ACTIVITY INC57BL 6 MICE/

The effects of age on the circadian clock system have been extensively studied, mainly in two rodent species, the laboratory rat and the gol den hamster. However, less information is available on how aging alter s circadian rhythmicity in a commonly studied rodent animal model, the mouse. Therefore, in the present study we compared the rhythm of whee l-running activity in adult (6-9 mo) and old (19-22 mo) C57BL/6J mice maintained under different lighting conditions for a period of 4 mo. D uring this period, mice were subjected to phase advances and phase del ays of the light-dark (LD) cycle and eventually to constant darkness ( DD). In LD (12 h light, 12 h dark), old mice exhibited delayed activit y onset relative to light offset and an increase in the variability of activity onset compared with adult mice. After a 4-h phase advance of the LD cycle, old mice took significantly longer to reentrain their a ctivity rhythm when compared with adult animals. Old mice also demonst rated a decline in the number of wheel revolutions per day and a tende ncy toward a decrease in the length of the active phase. An increase i n fragmentation of activity across the 24-h day was obvious in aging a nimals, with bouts of activity being shorter and longer rest periods i ntervening between them. No age difference was detected in the maximum intensity of wheel-running activity. In DD, the free-running period w as significantly longer in old mice compared with adults. In view of t he rapidly expanding importance of the laboratory mouse for molecular and genetic studies of the mammalian nervous system, the present resul ts provide a basis at the phenotypic level to begin to apply genetic m ethods to the analysis of circadian rhythms and aging in mammals.