In man, from childhood through senescence, there occur alterations in several metabolic functions that are regulated in part by the thyroid hormones. Thus, aging is associated with a decrease in basal oxygen consumption per unit surface area and an increase in total serum cholesterol and beta-lipoprotein cholesterol (1-5). Several indexes of thyroid function per se indicate greater thyroid activity in children and adolescents than in young adults and, conversely, less thyroid activity in the elderly. The extensive literature on this subject has been considered in recent publications (6, 7). It has been suggested, therefore, that there exist in childhood and senescence states of physiologic hyper-and hypothyroidism, respectively (4, 6, 8). It is not clear, however, whether this is truly the case. In this regard it may be significant that, in contrast to the situation in clinically recognizable thyroid disease, the serum protein-bound iodine (PBI) varies little, if at all, throughout the life-span of man (6,9,10).Recent studies related to these questions have indicated that the fractional rate of turnover of thyroxine (T4) in peripheral tissues decreases significantly from childhood through senescence (6,8,(10)(11)(12). Since variations in the binding of thyroid hormones to extracellular proteins greatly influence the kinetics of hormonal metabolism (13-15), the present studies were undertaken to determine whether the changes in the metabolism of T4 that accompany aging can be ascribed to
MethodsSera were obtained from 99 subjects ranging between 2 and 87 years of age. Except in the prepubertal group, all were males. All donors were in good health. In the older subjects, as would be expected, chronic degenerative disorders were present to a variable degree, but none were ill and all were engaged in their routine daily activities. None were hospital in-or outpatients.' No donor of blood was taking any medication known to influence the binding of thyroid hormone in serum. Sera were obtained from freshly drawn blood and were divided into several aliquots, which were quickly frozen and thawed only once before their use in a specific test.Since it was not possible to carry out any single analysis on all specimens at one time, specimens were divided into decade groups according to the age of their donor. In most instances, an equal number of specimens from each age group was analyzed concurrently. This minimized the possibility that any small differences among measurements in the several age groups could have been due to day-to-day variations in the analytic techniques. Measurements of the per cent of free T4 in serum, the distribution of "endogenous" T4 among the binding proteins, and the serum PBI, as well as tests of the in vitro resin uptake of 'MI-labeled triiodothyronine (T3) were, with few exceptions, performed in the same sera. For measurement of the T4-binding capacities of the thyroxinebinding globulin (TBG) and thyroxine-binding prealbumin (TBPA), however, sufficient quantities of these specimens were somet...