In the 1960s Cahill defined fasting in 3 phases with Phase II as fat using and protein conserving which is extended by animals adapted to long-term fasts without detrimental effects. Hibernation is a form of extreme fasting and black bears, Ursus americanus, undergo 5 months where they do not eat, drink, urinate or defecate while the body temperature is maintained only 5°C below normal. To accomplish this, they have a high hypothalamic set-point for fall hyperphagia and large fat reserve with a high proportion of polyunsaturated fatty acids. During transition to phase II there is elevated leptin, enhanced gut flora, decreased thyroxin and declining urea:creatinine ratios which together represent a period of fall “walking hibernation”. The inhibitory effect of leptin on neuropeptide Y from the arcuate nucleus may initiate the onset of anorexia and the bear’s entrance into their winter den. Bears are relatively unique in that they undergo pregnancy and lactation while fasting. There is 47% greater fat and 26% greater protein deposition for reproductive bears in the fall to offset their greater rate of mass and energy loss during denning. Long-term fasting in obese humans results in cardiac muscle protein loss and dysfunction, however, echocardiographic images of bears revealed no left ventricular resculpturing or reduced thickness during winter inactivity and chronic hypotension. Bears showed dramatic respiratory sinus arrhythmia with long pauses between breaths and profoundly depressed heart rates as low as 4 bpm. Accelerated heart rate during inhalation enhances oxygen transport within the heart tissue while the period of dramatically reduced heart rate acts to minimize energy expenditure and conserve cardiac protein. Skeletal muscle biopsies were taken from the biceps femoris, gastrocnemius and vastus lateralis during early and late denning. There was no loss of number, cross sectional area of fibers or marked transition of SO to FG fibers. Denning bears lost only about 0.03% protein/day, a value that is an order of magnitude below that reported for rats and humans, perhaps due to high ketone body inhibition of gluconeogenesis associated with a low thyroid activation of proteolysis and low urea:creatine ratio. This conservation of morphology and protein is atypical of starvation or disuse-induced skeletal muscle atrophy models. Bears underwent a period of skeletal muscle protein accretion with synthesis rates 1.4 times higher than degradation during the summer. Rates of synthesis and breakdown decreased 60-70% from summer to fall during the “walking hibernation” transition period with a concomitant 30-60% drop in RNA, a decreased ratio of RNA to DNA and an elevated δ 15N value in skeletal muscles. But all parameters then remained unchanged throughout the 5 months of denning without food or water. However, not all muscle behaves identically during fasting. There was a 4-11% loss of protein from the gastrocnemius and biceps femoris muscle by lactating bears but no loss from the vastus lateralis. Protein synthesis could occur in a selected muscle if amino acids are made available by the marginal degradation of other skeletal muscles in concert with proteolysis of organs, collagen and smooth muscle. The collagen metabolites hydroxyproline and glycine were elevated in denned bears. In addition, proteolysis of kidney tissue releases large amounts of serine that was high in late winter. The gastrointestinal tract may also be a labile protein source as seen in an elevation of blood alpha amino acids. Winter protein demands during the Phase II fast are further reduced by: 1) no winter arousal bouts, 2) delayed implantation for pregnant females, 3) no fur growth and 4) urea nitrogen salvaging (UNS) to avoid urinary nitrogen loss. Bears recycle almost 100% of their urea, perhaps due to UTB urea transporters in the bladder and intestines which salvage urea for microbial hydrolysis in the intestine. The resulting ammonia is transported to the liver where it is reamminated into new amino acids and muscle protein. UNS is upregulated in hibernators 10-40 fold during fasting and torpor as shown by 15N labeled urea studies. Bears exhibit subtle EMG patterns throughout the denning period with peripheral vasodilation which may disperse heat and facilitate wound healing. As a result of conserved protein, fiber morphology and isometric/isotonic contraction patterns, bears during 150 days of confinement and complete food deprivation exhibit only marginal loss of strength. Muscle performance measured both in vivo and in vitro declined only 23% from early to late winter compared to a 70% loss predicted for humans confined to a hospital bed (inactive but well fed) for 150 days. Bears are truly adapted long-term fasters.