Epigenetic hereditary transcription profiles II, aging revisited.
BACKGROUND
Previously, we have shown that deviations from the average transcription profile of a group of functionally related genes can be epigenetically transmitted to daughter cells, thereby implicating nuclear programming as the cause. As a first step in further characterizing this phenomenon it was necessary to determine to what extent such deviations occur in non-tumorigenic tissues derived from normal individuals. To this end, a microarray database derived from 90 human donors aged between 22 to 87 years was used to study deviations from the average transcription profile of the proteasome genes.


RESULTS
Increase in donor age was found to correlate with a decrease in deviations from the general transcription profile with this decline being gender-specific. The age-related index declined at a faster rate for males although it started from a higher level. Additionally, transcription profiles from similar tissues were more alike than those from different tissues, indicating that deviations arise during differentiation.


CONCLUSIONS
These findings suggest that aging and differentiation are related to epigenetic changes that alter the transcription profile of proteasomal genes. Since alterations in the structure and function of the proteasome are unlikely, such changes appear to occur without concomitant change in gene function. These findings, if confirmed, may have a significant impact on our understanding of the aging process.
Simons
Johannes Wim
JW
Department of Toxicogenetics, MGC, Leiden University Medical Center, PO Box 9600, 2300, RC Leiden, The Netherlands. j.w.i.m.simons@lumc.nl
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D046988:Proteasome Endopeptidase Complex / Q000235:genetics; D012727:Sex Characteristics; D014158:Transcription, Genetic; D055815:Young Adult
D046988:Proteasome Endopeptidase Complex