POTENTIALLY PREDICTIVE AND MANIPULATABLE 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

A cross sectional survey was made in 56 exceptionally healthy males, r anging in age from 20 to 84 years. Measurements were made of selected steroidal components and peptidic hormones in blood serum, and cogniti ve and physical tests were performed. Of those blood serum variables t hat 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 hor mone (GH) showed a stepwise pattern of age-related changes most closel y resembling those of the age steps themselves. Of these, BT correlate d best with significantly age correlated cognitive and physical measur es. Because DHEAS correlated well with BT and considerably less well t han 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 dir ect role in whatever processes are rate-limiting in the functions meas ured and that DHEAS relates more indirectly to these functions. The hi gh correlation of IGF-1/GH with age, its relatively low correlation wi th BT, and the patterns of correlations of IGF-1/GH and BT with signif icantly age-correlated cognitive and physical measures suggest that th e GH-IGF-1 axis and BT play independent roles in affecting these funct ions. Serial determinations made after oral ingestion of pregnenolone and data from the literature suggest there is interdependence of stero id metabolic systems with those operational in control of interrelatio ns in the GH-IGF-1 axis. Longitudinal concurrent measurements of serum levels of BT, DHEAS, and IGF-1/GH together with detailed studies of t heir correlations with age-correlated functional measures may be usefu l in detecting early age-related dysregulations and may be helpful in devising ameliorative approaches.