Although there is a large body of data showing an age-associated decline in the physiological systems of mammals, there is a great need for more descriptive information on the morphological and functional changes that occur with age. A powerful approach for ascertaining the extent to which age-related physiological changes limit the functional capacity of mammals is to study the effects of age on the response to challenges. Food restriction that markedly increases the mean life span of rodents also provides a potentially effective experimental probe of the aging process. Results are reported from our current research on morphologic and functional changes during the total life span of rats and on the influence of food restriction on these age-related changes. The data from our study of the lean body mass, adipose tissue mass, and adipose tissue structure indicate that current dogmas need to be reexamined; moreover, they clearly show the need for and the power of life-long descriptive studies. Our research on the influence of food restriction on age-related changes in functional activity supports the hypothesis that one mechanism by which food restriction increases the life span of rats relates to the delay in time of onset and a change in chronologic course of physiologic decline.