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Dehydroepiandrosterone sulfate (DHEAS), the major circulating adrenal hormone, has been suggested to have a role in many aging related diseases and perhaps in aging itself. Its precise biologic effects are still unknown, and data on healthy people over 90 yr of age are not available. We measured serum DHEAS levels in 75 healthy subjects aged 90-106 yr of both sexes and searched for correlations between DHEAS and several endocrine-metabolic parameters (serum thyroid hormones, GH-insulin-like-growth factor I (GH-IGF-I) axis, serum lipid profile, anthropometric indices of body composition) of the same subjects. The resulting data, normalized by logarithmic transformation (geometric mean at age 90-99, 551 ng/mL in men, 364 ng/mL in women; at age > 100 yr, 404 ng/mL in men, 521 ng/mL in women) resulted five-fold lower than DHEAS levels measured in a young control group (geometric mean at < 40 yr of age, 3110 ng/mL in men, 2824 ng/mL in women). In women over ninety yr, DHEAS was positively correlated with serum free triodothyronine (FT3) levels (r = 0.34, P = 0.05) and inversely with triglycerides (r = -0.45, P = 0.05). In men over 90 yr, DHEAS had positive correlations with body mass index (r = 0.41, P < 0.03) and waist-to-hip ratio (r = 0.47, P < 0.01) taken as indices of body's energy reserves (fat). To determine whether low serum DHEAS levels predict poor functional status in the very old, the Activity Daily Living (ADL) test was administered in all over-ninety subjects. Men with the highest functioning levels had the highest DHEAS levels (P < 0.03). Our data suggest that DHEAS levels may influence and/or be influenced by several endocrine and metabolic features of oldest-old people, depending on the sexual steroid milieu. DHEAS seems also to have a strong interrelation with functional activities. A favorable role for DHEAS in successful aging is proposed.