Age-related changes in signal transduction. Implications for neuronal transmission and potential for drug intervention.

Problems associated with aging will become one of the leading health dilemmas of the next century. Age-associated diseases, including those affecting the neuronal system, are increasing in frequency. Age-related deficiencies in the brain result in impaired motor functions, sleep, behaviour and cognitive functions. Good functioning of the brain is based on the communication between neurons, by means of signal sending and processing. Neuronal transmission is a very complex phenomenon which involves neuromediator receptors, ion channels and various signal transduction systems. Aging is associated with modification of many brain neurotransmitter and second messenger systems directly involved in signal transduction. Thus, signal transduction events that are deficient in the aged include calcium mobilisation, phosphatidylinositol breakdown, cyclic nucleotides formation, accumulation of proto-oncogene transcripts and synthesis of new proteins, such as certain neurotransmitters. Other events in signal transduction, such as protein tyrosine kinase activity, G-protein structure and function and receptor-G-protein coupling, have not been studied in great detail as yet. Alterations in these various intracellular signalling events may fundamentally influence the functional activity of neurons, and, in consequence, play an important role in the age-dependent alterations of brain functions. Future studies are needed to better understand the molecular basis and the importance of signal transduction changes with aging. Such knowledge will certainly lead to design of better drugs for the prevention or treatment of age-related deficiencies or diseases, such as Parkinson's disease or Alzheimer's disease.