Neuronal Shc: a gene of longevity in the brain?

Aging is inevitable to all multi-cellular organisms, and each organism has its own lifespan. The species-specific lifespan seems determined genetically; however little is known about how the lifespan determined. During the last decades accumulative evidence indicates that there is certainly a set of genes that are involved in the lifespan determination. Among those dozens of genes, the Shc gene encoding a phosphotyrosine signal adaptor is of potential interests in mammalian aging and/or longevity determination. Shc is merely one form of a gene family, and accumulative evidence demonstrates the presence of additional Shc homologues that are strongly expressed in the nervous system. We hypothesize that lifespan is regulated primarily by the nervous system and/or brain, and neurally expressed Shc homologues play pivotal roles in relation to the evolution of longevity with quality of life. We discuss herein the recent progress of our understanding of the neuronally expressed Shc genes in comparision with p66-Shc as a candidate for the evolution of long life with higher quality of life in mammals.