Influences of aging and caloric restriction on the transcriptional profileof skeletal muscle from rhesus monkeys

In laboratory rodents, caloric restriction (CR) retards several age-depende nt physiological and biochemical changes in skeletal muscle, including incr eased steady-state levels of oxidative damage to lipids, DNA, and proteins. We have previously used high-density oligonucleotide arrays to show that C R can prevent or delay most of the major age-related transcriptional altera tions in the gastrocnemius muscle of C57BL/6 mice. Here we report the effec ts of aging and adult-onset CR on the gene expression profile of 7.070 gene s in the vastus lateralis muscle from rhesus monkeys. Gene expression analy sis of aged rhesus monkeys (mean age of 26 years) was compared with that of young animals (mean age of 8 years). Aging resulted in a selective up-regu lation of transcripts involved in inflammation and oxidative stress, and a down-regulation of genes involved in mitochondrial electron transport and o xidative phosphorylation, Middle-aged monkeys (mean age of 20 years) subjec ted to CR since early adulthood (mean age of 11 years) were studied to dete rmine the gene expression profile induced by CR, CR resulted in an up-regul ation of cytoskeletal protein-encoding genes, and also a decrease in the ex pression of genes involved in mitochondrial bioenergetics, Surprisingly, we did not observe any evidence for an inhibitory effect of adult-onset CR on age-related changes in gene expression. These results indicate that the in duction of an oxidative stress-induced transcriptional response may be a co mmon feature of aging in skeletal muscle of rodents and primates, but the e xtent to which CR modifies these responses may be species-specific.