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A general feature of all aging populations is the progressively impaired ability to adapt to changes in the surrounding environment. Biochemical expressions of adaptive response include modifications in the rates of enzyme synthesis and degradation, as well as alterations in physiological activity. Therefore, the effects of aging on enzyme adaptation were surveyed in an attempt to explore fundamental biochemical mechanisms in the deterioration of responsiveness. The ability to stimulate adaptive increases in the activity of a large number of enzymes is impared during aging in a variety of tissues from several different species. The impaired capability for liver enzyme adaptation in a rigorously controlled colony of aging male Sprague-Dawley rats probably reflects alterations in hormonal control mechanisms. The present article reviews and evaluates our interest in understanding the effects of aging on regulation of liver enzyme activity by the hormones, insulin and corticosterone. Specific areas currently under investigation include: (1) the regulation of their concentrations in blood; (2) the integrity of their receptor systems in liver; and (3) effectiveness of the endogenous hormone pools fromthe viewpoints fothe availability of physiological antagonists and the potential for alterations in molecular structure.

Factors contributing to modifications in the capability for enzyme adaptation as an expression of aging are reviewed. Specific examples of altered enzyme adaptations during aging include the responses of hepatic glucokinase activity to glucose and hepatic tyrosine aminotransferase activity to starvation in Sprague-Dawley rats. These impaired enzyme adaptations apparently are not the consequence of alterations in hepatic function during aging. Instead, they reflect disturbances in extrahepatic hormonal regulatory mechanisms. Specific examples include modifications in the control of circulating levels of insulin glucagon, corticosteroids, and thyroid hormones. Age-dependent changes in the regulation of circulating levels of insulin probably originate within the impaired ability of pancreatic islets of Langerhans to secrete the hormone in response to glucose. The rationale for exploiting this experimental approach as a means to understand biological aging is discussed.