The aging-induced decrease in non-shivering thermogenic capacity was prevented in the genetically CCK-A receptor deficient, diabetic obese OLETF rats, provably by an increase in the responsiveness of BAT to glucagon. The potential metabolic capacities can be sustained until aged period. Body temperature is determined by the balance of heat dissipation from the body surface and respiration, and heat production. Under cold conditions, heat production is stimulated by shivering and non-shivering thermogenesis (thermogenesis without shivering: NST) in addition to the suppression of heat dissipation from the skin by cutaneous vasoconstriction, resulting in preventing hypothermia. During the process of cold acclimation, the heat production by NST substitutes for the one by shivering, and therefore a capacity for cold tolerance may mainly depend on the NST activity. The major factor stimulating NST is norepinephrine (NA) released from sympathetic nerves. 1 The major site of NST is brown adipose tissue (BAT). In contrast to usual adipose tissue (white adipose tissue), BAT is densely innervated with sympathetic nerves and is rich in vascular distribution. BAT is a unique tissue of which the sole task is thought to be heat production. 2 Norepinephrine acts on brown adipocytes via adrenergic b 3 receptor, causing the production of cAMP as an intracellular second messenger. cAMP activates protein kinase which is then followed by the activation of hormone-sensitive lipase, and finally hormonesensitive lipase resolves triglyceride. The free fatty acids (FFA) thus produced are transferred to the mitochondrion as a fuel, and the excess FFA as well as glycerol is released as a substrate for other tissues. Thermogenic activity of BAT is enhanced by cold exposure, overfeeding, adrenergic stimulation, and immobilization stress, and suppressed by heat exposure, obesity, and aging. 3 Brown adipocyte has numerous mitochondria, and the specific thermogenic activity of the cell is attributable to the restriction of oxidative phosphorylation by an uncoupling protein (UCP) on the inner membrane of the mitochondrion. In general, mitochondrial oxidation of fuels generates an electrochemical gradient via an outward pumping of protons by the electron transport chain. ATP production via ATP synthetase is then facilitated by the inward flux of protons down the gradient. However, in brown adipocyte mitochondrion the electrochemical gradient is counteracted by a proton influx via UCP, causing an uncoupling of oxidative phosphorylation, accompanied by the heat generation without ATP production. 4 Glucagon is a potent stimulator of BAT comparable with NA. The effect of glucagon on BAT may be suppressed by prolactin, probably through the inhibition of the intracellular signaling route via IP 3 -Ca 2+ , being important for NST stimulation by glucagon. It is assumed that glucagon plays a significant role when the responsiveness of BAT to NA is not fully established, such as the neonatal period and beginning stage of cold acclimation. 5 Aging attenuates...