Gene expression profile of the aging brain.
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Biomedical subjects
Publications and source records attributed to Richard Weindruch.
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We have previously employed high density oligonucleotide arrays representing thousands of genes to determine the gene expression profile of the aging process in skeletal muscle (gastrocnemius) and brain (cerebellum and neocortex) of male C57BL/6 mice. Specific gene expression profiles are associated with the aging process of individual organs, and caloric restriction can prevent or retard the establishment of these gene expression alterations. The use of DNA microarrays may provide a new tool to measure biological age on a tissue-specific basis and to evaluate at the molecular level the efficacy of interventions designed to retard the aging process.
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The retardation of aging and diseases by caloric restriction (CR) is a widely-studied and robust phenomenon. Recent publications describe transgenic and other mutant rodents displaying lifespan extension, and the rapid pace at which these animals are being generated raises the possibility that the importance of the CR paradigm is declining. Here we discuss these models and evaluate the evidence whether or not the aging process is retarded based on longevity, disease patterns and age-associated biological changes. A comparison to rodents on CR is made. Because CR has been investigated for approximately 70 years with increasing intensity, there exists extensive data to document aging retardation. In contrast, for nearly all of the genetically abnormal models of lifespan extension, such data are minimal and often unconvincing; additional studies will be required to validate these strains as suitable models for aging research.
OBJECTIVES: Our purpose is to highlight some of the past and potential future uses of microarray in nutrition research, while also commenting on some aspects of the design conduct and analysis of microarray data that will leave to improved data quality. METHODS: In this review article we outline some of the aspects of microarray experimentation that must be considered before and during these experiments. These topics include: identification of the experiment's objective (hypothesis), the experimental design, sample size, statistical analysis, data verification, data handling, and experimental interpretation. RESULTS: In order to illustrate the principles we outline in this article we use the methods to layout the design of a microarray experiment to study one aspect of the observation that a diet high in soy is associated with lower rates of breast cancer. CONCLUSIONS: Microarrays are a very powerful tool for studying virtually every nutrition-related disease and trait and can provide valuable insights that are not obtainable with other techniques. However, unless nutrition researchers conduct their studies with scientific hard-mindedness, the studies will be of lower power at least if not completely misleading.
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