Lessons learned from gene expression profile studies of aging and caloric restriction.

To examine molecular events associated with aging and its retardation by caloric restriction (CR), we have employed high-density oligonucleotide microarrays to define transcriptional patterns in mouse tissues, including skeletal muscle, brain, heart, and adipose. Aging results in a differential gene expression pattern specific to each tissue, and most alterations can be completely or partially prevented by CR. Transcriptional patterns of tissues from calorie-restricted animals suggest that CR retards the aging process by reducing endogenous damage and by inducing metabolic shifts associated with specific transcriptional profiles. These studies demonstrate that DNA microarrays can be used in aging research to generate panels of hundreds of transcriptional biomarkers, providing a new tool to measure biological age on a tissue-specific basis and to evaluate interventions designed to mimic the effects of CR.