E-GEOD-6323 - Transcription profiling of skeletal muscles from young, old, and old calorie restricted C57BL/6NHsd mice to investigate age-related changes in the transcriptional profile.
Submitted on 20 November 2006, released on 13 November 2007, last updated on 27 March 2012
We investigated age-related changes in the transcriptional profile of skeletal muscle in 5 month old (young) and 25 month old (old) C57BL/6NHsd mice using high density oligonucleotide arrays (22,690 transcripts probed). We identified 712 transcripts that are differentially expressed in young (5 month old) and old (25-month old) mouse skeletal muscle. Caloric restriction (CR) completely or partially reversed 87% of the changes in expression. Examination of individual genes revealed a transcriptional profile indicative of increased p53 activity in the older muscle. To determine whether the increase in p53 activity is associated with transcriptional activation of apoptotic targets, we performed RT-PCR on four well known mediators of p53-induced apoptosis: puma, noxa, tnfrsf10b and bok. Expression levels for these proapoptotic genes increased significantly with age (P<0.05), while CR significantly lowered expression levels for these genes as compared to control fed old mice (P<0.05). Age-related induction of p53-related genes was observed in multiple tissues, but was not observed in SOD2+/- and GPX4+/- mice, suggesting that oxidative stress does not mediate the observed age-related increase in expression. Western blot analysis confirmed that protein levels for both p21 and GADD45a, two established transcriptional targets of p53, were higher in the older muscle tissue. These observations support a role for p53-mediated apoptotic activity in mammalian aging. Experiment Overall Design: Animals were killed by cervical dislocation. Five different animals were used for each experimental group. All collected gastrocnemius tissue was then dissected, placed in a microcentrifuge tube, flash-frozen in liquid nitrogen, and stored at -80°C until processed for microarrays.
transcription profiling by array, co-expression, development or differentiation
Gene expression profiling of aging reveals activation of a p53-mediated transcriptional program. Michael G Edwards, Rozalyn M Anderson, Ming Yuan, Christina M Kendziorski, Richard Weindruch, Tomas A Prolla. BMC Genomics 8:80 (2007)