Potentially predictive and manipulable blood serum correlates of aging in the healthy human male: progressive decreases in bioavailable testosterone, dehydroepiandrosterone sulfate, and the ratio of insulin-like growth factor 1 to growth hormone

Abstract

A cross-sectional survey was made in 56 exceptionally healthy males, ranging in age from 20 to 84 years. Measurements were made of selected steroidal components and peptidic hormones in blood serum, and cognitive and physical tests were performed. Of those blood serum variables that gave highly significant negative correlations with age (r > -0.6), bioavailable testosterone (BT), dehydroepiandrosterone sulfate (DHEAS), and the ratio of insulin-like growth factor 1 (IGF-1) to growth hormone (GH) showed a stepwise pattern of age-related changes most closely resembling those of the age steps themselves. Of these, BT correlated best with significantly age-correlated cognitive and physical measures. Because DHEAS correlated well with BT and considerably less well than BT with the cognitive and physical measures, it seems likely that BT and/or substances to which BT gives rise in tissues play a more direct role in whatever processes are rate-limiting in the functions measured and that DHEAS relates more indirectly to these functions. The high correlation of IGF-1/GH with age, its relatively low correlation with BT, and the patterns of correlations of IGF-1/GH and BT with significantly age-correlated cognitive and physical measures suggest that the GH-IGF-1 axis and BT play independent roles in affecting these functions. Serial determinations made after oral ingestion of pregnenolone and data from the literature suggest there is interdependence of steroid metabolic systems with those operational in control of interrelations in the GH-IGF-1 axis. Longitudinal concurrent measurements of serum levels of BT, DHEAS, and IGF-1/GH together with detailed studies of their correlations with age-correlated functional measures may be useful in detecting early age-related dysregulations and may be helpful in devising ameliorative approaches.

Figures

Figure 1

Stepwise age-related changes. (A) The age curve was obtained by plotting the median age of a particular cohort (Table 2) vs. median age of the 20–29-yr cohort/median age of the particular cohort. The curves for the biochemical variables were obtained by plotting the median age of a particular cohort vs. the mean value (ng/ml) for the variable in the cohort/the mean value for the 20–29-yr cohort. (B) Plot of the actual serum values of BT, DHEAS, and IGF-1/GH as a function of median age of the cohort.

Figure 2

Effect of ingestion of P on blood serum levels of steroids, IGF-1, and GH. All values in bold type are higher than the control values. The biosynthesis of steroid hormones begins with cholesterol, from which the sex steroids (e.g., T), glucocorticoids (e.g., cortisol), and mineralocorticosteroids (e.g., aldosterone) all derive. P is believed to be a major precursor for the steroid hormones. It is formed from cholesterol in mitochondria of tissues that produce steroid hormones (consult ref. for discussion of biochemical details).

Figure 3

Changes in serum levels of several pertinent variables at intervals over an 8-hr period after preprandial oral ingestion of 175 mg of P by two healthy males. The values are expressed as ratios of the values at various times after ingestion of P to those observed before ingestion. The 24-hr values are not shown on the plot but are recorded in Fig. 2.

Figure 4

Serum levels of T as a function of levels of DHEAS. In C, the SEM for the mean values is shown by the lines through the data points.