Brain Growth Receptors Control Lifespan 英文参考文献.docVIP

Brain Growth Receptors Control Lifespan Richard Robinson | doi:10.1371/journal.pbio.0060274 When resources are short, growing organisms face an existential choice: should you ignore the shortage and hope for better times soon, or scale back and live within your limited means? And if you do scale back, will there be any payoff later in life? For animals, these choices are played out hormonally, with environmental fluctuations leading to internal rearrangements in endocrine signal and response throughout the growing body. In mammals, two principal hormones—growth hormone (GH) and insulin-like growth factor 1 (IGF- 1)—promote growth. Remarkably, inhibiting one or both of these two not only retards growth, but also extends lifespan, not just in lab animals, but possibly also in people: mutations that reduce the function of the IGF-1 doi:10.1371/journal.pbio.0060274.g001 receptor have recently been discovered in centenarians (who are also short). Growth occurs throughout the body, and receptors for IGF-1 are found in every organ on virtually every cell. But Laurent Kappeler et al. now show that it is the IGF-1 receptors in the brain that set the pattern for growth and lifespan. The authors were led to the brain by the hierarchy of the endocrine system itself. While the pituitary gland, which sits just beneath the cranium, is often called the “master gland,” it is really more of a first mate, taking its orders directly from the brain’s hypothalamus. The hypothalamus controls differentiation and daily function of the pituitary, sending it instructions in the form of “releasing hormones,” including growth hormone releasing hormone (GHRH). The pituitary, in turn, releases its own corresponding hormones into the blood stream, including growth hormone, which travels to the liver, triggering the production of IGF-1. Collectively, this cascade is known as the “somatotropic axis,” and the authors reasoned that if the axis is ultimately controlled from the brain, then its abil