Aging Clin Exp Res, Vol. 16, No. 6 423 In 2003, Anson et al. (1) published some surprising findings: when C57BL/6 mice were given unlimited access to food one day and fasted the next day, from age 9 through 38 weeks, their total caloric intake was similar to that of mice with continuous access to food (i.e., ad libitum-fed), and this “every other day feeding” regime had beneficial effects on both carbohydrate metabolism and resistance of neurons to injury. In fact, the beneficial effects were even more pronounced with mice on the “every other day feeding” regime than with mice whose daily caloric intake was restricted to 60% of that of mice with continuous access to food. The authors suggested that “every other day feeding” may extend life by means other than reducing caloric intake, but their research provided no such information, since the duration of “every other day feeding” was only 29 weeks and the mice were about 9 months of age at the end of the study. Moreover, Duffy et al. (2) reported that longterm “every other day feeding” of mice did result in a 40% reduction in caloric intake. However, it must be noted that all experimental paradigms in caloric restriction studies have involved fasting periods of varying durations, depending on the study design (3). Thus, the anti-aging action that has been attributed to caloric restriction might instead relate to the occurrence of periodic fasting. This possibility certainly warrants further study. Indeed, an attempt was made in our laboratory to address this issue by comparing the effects of caloric restriction in rats whose daily allotment of food was provided in a single meal at 15:00 h or in two daily meals at 07:00 h and 15:00 h (4). Both of these procedures resulted in the same increase in longevity, leading us to conclude that energy intake rather than temporal pattern of food intake is the factor responsible for life extension. However, these findings do not conclusively eliminate the role of periodic fasting, since even in this twice-a-day feeding paradigm daily brief periods of fasting are likely. Caloric intake versus temporal pattern of food intake