Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota, USA Pituitary hormones drive target glands, such as the testis, ovary and adrenal, to secrete anabolic and stress-adaptive hormones. An early contribution by Dr. Veldhuis was a deconvolution method to quantify secretion without hormone infusion (Proc Natl Acad Sci USA 84: 7886-90, 1987). Subsequent focus has been on anabolic hormones. Anabolic signals are critical to preserve vigor and well being in aging by maintaining bone mass, muscle strength, glucose and lipid metabolism, sexual function, well being memory and cognition. A parallel emphasis is on sex differences. For example, gradual depletion of gender-specific gonadal sex-steroids in postmenopausal women and healthy aging men augments the risk of osteoporosis, sarcopenia, glucose intolerance, visceral adiposity, atherosclerotic disease, and mood and cognitive deficits. Albeit imperfectly understood, key loci of sex-hormone control include the potent peptide, insulin-like growth factor type I [IGF-I] and the life-preserving stress-adaptive hormone, cortisol (Proc Natl Acad Sci USA 98: 4028-33, 2001). To investigate the bases of gender and age-related failure of IGF-I production and increased cortisol availability, Dr. Veldhuis’ research team has developed a novel combined experimental and analytical platform to link the time-varying actions of blood-borne hormone signals to tissue responses in the unmedicated and uninfused human (Proc Natl Acad Sci USA 101: 6740-45, 2004). This technology reveals that one of the earliest detectable changes in aging is erosion of system-level or ensemble regulation of the secretion of testosterone, estradiol, IGF-I and insulin (Proc Natl Acad Sci USA 93: 14100-05, 1996). What remains fundamentally unknown is how aging disrupts homeostatic coordination among these hormonal axes. Dr. Veldhuis’ work exploits a strong infrastructure of National Institutes of Health support to investigate the specific mechanisms mediating impaired regulation of the countervailing catabolic and anabolic hormones, cortisol and IGF-I, in healthy aging men and women. This research strategy assumes that: (a) establishing very early alterations in human aging will help to unmask the primary mechanisms that drive later signs and symptoms of frailty; (b) physiological homeostasis requires a precise counterbalance between tissue renewal (anabolism) and breakdown (catabolism); and (c) aging forces the expected equipoise of anabolism and catabolism toward catabolism, and thereby impeding organ recovery in aging during stress, illness and injury. The long-term expectation of this focus is to stimulate safe and effectual interventions to obviate trophic hormone depletion in the aging population, and thereby enhance quality of life, extend productivity and limit disability in older individuals.