'GeriatrieResearch, Education and ClinicalCenter, Veterans Administration PugetSoundHealthCare System, and 2Division of Gerontology and Geriatrie Medicine, Departrnent of Medicine, and 3Population Centerfor Researchin Reproduction, University ofWashingtonSchoolofMedicine, Seattle. AGING is associated with altered body composition (fat and ./'"\..lean mass and bone mineralcontent) in humans (1-6), nonhuman primates(7), rats (8-10), and other animals,and with adverse physiological consequencesrelatedto changes in the body habitus. Adipose tissue mass increases from middle to old age, and is associated with insulin resistance and impaired glucose tolerance, which contribute to development of Type 2 diabetes (NIDDM) and its sequelae (11)(12)(13)(14). An age-associated decrease oflean mass, specifically skeletalmuscle mass (sarcopenia), results in weakness, poor immune function, and impaired thermoregulation (2,6,15). In humans,decreasedbone mass is a hallmark of aging. Bone mineral density and content decrease in women after menopause, but also in aged men, and may lead to osteoporosis and an increasedrate of debilitating fractures (3,16). The mechanisms underlyingthese changesin body composition are unclear. However, alterations in the endocrinesystemare implicated, includingdecreased levelsof trophic hormones (estrogen, testosterone,and growth hormone/insulin-like growth factor-1 [IGF-1]) and increasedinsulin levels (l, 17).We have been investigatingthe neuroendocrinemechanisms of age-related alterations in reproductive function, and energy (food intake and body weight) regulation in the male Brown Norway rat, and have found it to be a very good model of human aging. Compared to outbred strains, the genetic homogeneity of this inbred rat model ensures greater uniformity of responsesto experimentalmanipulations, with smaller numbers of animals needed. The National Instituteof Aging maintains a breeding colony of Brown Norway BN/Bi (BN) rats in a specific pathogen-free environment, ensuring a long disease-free survival rate; this colony has a 50% survival age of 32 months for males (18). The use of this strain of rat as a model of human aging has several advantages over other strains that are commonly used in biomedical research. Unlike Fischer 344 (F344) or F344/BN hybrid rats (18,19), Brown Norway rats do not develop pituitary tumors that result in gonadotropin deficiency and/or hyperprolactinemia, or testicular tumors producing excessive amounts ofprogesterone, nor do they develop the extreme obesity that is common to many inbred strains of ratsall conditions that would confound studies of reproduction and energy balance. In contrast to other aging rat models, glomerulonephritisand pneumonitis are rare in Brown Norwayrats, and testicular function is maintained until old age when serum testosterone levelsdecline (20).We reported previously that aging Brown Norwayrats exhibited reduced rates of food intake and body weight gain, accompanied by decreased expression of neuropeptideY (NPY, a potent neuropeptide stimula...