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 insulinlike 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 and͞or 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-1͞GH with age, its relatively low correlation with BT, and the patterns of correlations of IGF-1͞GH 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-1͞GH together with detailed studies of their correlations with agecorrelated functional measures may be useful in detecting early age-related dysregulations and may be helpful in devising ameliorative approaches.

Cortisol/Dehydroepiandrosterone Ratio and Responses to Antipsychotic Treatment in Schizophrenia

“…They serve as a precursor to the sex hormones estradiol and testosterone and their serum levels decrease with age in healthy individuals. DHEA(S) also function as neurosteroids (Morley et al, 1997;Nafziger et al, 1998;Binello and Gordon, 2003).…”

Vieillissement et rythmes biologiques chez les primates

“…D'une façon générale, et dans les deux sexes, les rythmes journaliers des hormones sexuelles présents chez l'adulte s'affaiblissent ou disparaissent au cours du grand âge [2,15,[17][18][19][20]. Pour le microcèbe, primate à reproduction saisonnière, les variations saisonnières de testostérone plasmatique persistent avec une grande amplitude jusqu'à un âge très avancé (6-7 ans) puis disparaissent.…”

Endocrine and metabolic changes in human aging

“…In the absence of adrenal insufficiency (43), studies in humans have been controversial, with high dose DHEA (100 mg per day) increasing muscle mass in males (44) but having varied effects on immune function (44) and behavior (45,46). Pregnenolone, the precursor adrenal hormone, also declines with age (47). It has positive effects on arthritis (48) and appears to have a wide safety margin.…”