PMID- 12044943 OWN - NLM STAT- MEDLINE DCOM- 20020917 LR - 20190901 IS - 0047-6374 (Print) IS - 0047-6374 (Linking) VI - 123 IP - 8 DP - 2002 Apr 30 TI - Brain evolution and lifespan regulation: conservation of signal transduction pathways that regulate energy metabolism. PG - 947-53 AB - Mechanisms for sensing, acquiring, storing and using energy are fundamental to the survival of organisms at all levels of the phylogenetic scale. Single-cell organisms evolved surface receptors that sense an energy source and, via signal transduction pathways that couple the receptors to the cell cytoskeleton move towards the energy source. Mutlicellular organisms evolved under conditions that favored species that developed complex mechanisms for obtaining food, with nervous systems being critical mediators of energy acquisition and regulators of energy metabolism. A conserved signaling system involved in regulating cellular and organismal energy metabolism, and in sensing and responding to energy/food-related environmental signals, involves receptors coupled to the phosphatidylinositol-3-kinase-Akt signaling pathway. Prominent activators of this pathway are insulin, insulin-like growth factors and brain-derived neurotrophic factor (BDNF). Recent studies in diverse organisms including nematodes, flies and rodents have provided evidence that insulin-like signaling in the nervous system can control lifespan, perhaps by modulating stress responses and energy metabolism. Interestingly, the lifespan-extending effect of dietary restriction in rodents is associated with increased BDNF signaling in the brain, and a related increase of peripheral insulin sensitivity, suggesting a mechanism whereby the brain can control lifespan. Thus a prominent evolutionarily conserved function of the nervous system is to regulate food acquisition and energy metabolism, thereby controlling lifespan. FAU - Mattson, Mark P AU - Mattson MP AD - Laboratory of Neurosciences, National Institute on Aging Gerontology Research Center 4F01, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA. mattsonm@grx.nia.nih.gov LA - eng PT - Journal Article PT - Review PL - Ireland TA - Mech Ageing Dev JT - Mechanisms of ageing and development JID - 0347227 SB - IM MH - Animals MH - *Biological Evolution MH - Brain/*metabolism MH - Energy Metabolism MH - Eukaryotic Cells MH - Humans MH - Longevity/*physiology MH - *Signal Transduction RF - 61 EDAT- 2002/06/05 10:00 MHDA- 2002/09/18 10:01 CRDT- 2002/06/05 10:00 PHST- 2002/06/05 10:00 [pubmed] PHST- 2002/09/18 10:01 [medline] PHST- 2002/06/05 10:00 [entrez] AID - S0047637402000325 [pii] AID - 10.1016/s0047-6374(02)00032-5 [doi] PST - ppublish SO - Mech Ageing Dev. 2002 Apr 30;123(8):947-53. doi: 10.1016/s0047-6374(02)00032-5.