of this hormone were found to be significantly lower in young patients with myocardial infarction. These findings may prompt further research into the role played by irisin not only in vascular disorders but also in life span modulation. Fibroblast Growth Factor 21 Production (FGF-21) has been documented as a pathway to longevity. BAT activation through cold exposure up-regulates circulating fibroblast growth factor 21 (FGF21) in humans by 37%. FGF21 improves insulin sensitivity and glucose metabolism which may partially explain its longevity promoting benefits. Under basal environmental temperatures, HDAC3 primes expression of UCP1 and the brown fat thermogenic program to ensure acute cold survival through the deacetylation and activation of PGC-1alpha. Cold exposure increases SIRT1 phosphorylation/activity in both skeletal muscle and BAT, increasing thermogenesis and insulin sensitivity through deacetylation of PGC-1alpha and other protein targets. Elevated SIRT1 levels in people are associated with increased human longevity. SIRT1 (and the other sirtuins) have many metabolic effects, but an important one for improving health and longevity is the fact that SIRT1 increases insulin sensitivity and glucose control in skeletal muscles, triggers the browning of white fat and increases BAT activity. Other animals The interscapular brown adipose tissue is commonly and inappropriately referred to as the hibernating gland. Whilst believed by many to be a type of gland, it is actually a collection of adipose tissues lying between the scapulae of rodentine mammals. Composed of brown adipose tissue and divided into two lobes, it resembles a primitive gland, regulating the output of a variety of hormones. The function of the tissue appears to be involved in the storage of medium to small lipid chains for consumption during hibernation, the smaller lipid structure allowing for a more rapid path of energy production than glycolysis. In studies where the interscapular brown adipose tissue of rats were lesioned, it was demonstrated that the rats had difficulty regulating their normal body-weight. The longest-lived small mammals, bats (30 years) and naked mole rats (32 years), all have remarkably high levels of brown adipose tissue and brown adipose tissue activity. However, brown fat is unlikely to play a role in body temperature regulation of many large-bodied mammals as the UCP1 gene, encoding for the key thermogenic protein of the tissue, has been inactivated in several lineages (e.g. horses, elephants, sea cows, whales and hyraxes). A reduced surface area to volume ratio among large-bodied species decreases heat loss in the cold,