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    Genomic profiling of short and long-term caloric restriction effects in the liver of aging mice

    Cao, S.X., Dhahbi, J.M., Mote, P.L., and Spindler, S.R.

    The PNAS , September 2001, 98: 10630-10635, .


    Genome-wide microarray expression analysis of 11,000 genes in an aging potentially mitotic tissue, the liver, was performed. Liver has a major impact on health and homeostasis during aging. The effects of life- and health-span-extending CR (caloric restriction) on gene expression among young and old mice and between long-term CR (LT-CR) and short-term CR (ST-CR) were examined. Aging was accompanied by changes in gene expression associated with increased inflammation, cellular stress, and fibrosis, and reduced capacity for apoptosis, xenobiotic metabolism, normal cell-cycling, and DNA replication. LT-CR and just 4 weeks of ST-CR reversed the majority of these changes. LT-CR produced in young mice a pattern of gene expression that is a subset of the changes found in old LT-CR mice. It is possible that the early changes in gene expression, which extend into old age, are key to the life- and health-span-extending effects of CR. Further, ST-CR substantially shifted the "normo-aging" genomic profile of old control mice toward the "slow-aging" profile associated with LT-CR. Expression profiling should prove useful in quickly identifying CR-mimetic drugs and treatments.