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Epigenetic hereditary transcription profiles II, aging revisited.

Simons JW - Biol. Direct (2007)

Bottom Line: The age-related index declined at a faster rate for males although it started from a higher level.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Toxicogenetics, MGC, Leiden University Medical Center, PO Box 9600, 2300, RC Leiden, The Netherlands. j.w.i.m.simons@lumc.nl

ABSTRACT

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.

Conclusion: 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.

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Related in: MedlinePlus

Mean profiles of 2nd-log obs/exp for the two classes obtained with k-means clustering.
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Figure 2: Mean profiles of 2nd-log obs/exp for the two classes obtained with k-means clustering.

Mentions: The remaining variation in "2nd-log obs/exp" could be due either to factors associated with nuclear programming, such as gender, age and tissue specificity or to other factors such as post-mortem changes (if the biopsy was obtained by autopsy), 'noise' in transcription or experimental error. Also individual specificity in the transcription profile is, in theory, possible and belongs with the first factor type. To determine the possible influence of such factors, the libraries were divided into 2 classes by k-means clustering. The mean "2nd log obs/exp", that indicate the deviations from expected transcription profiles, are depicted in Figure 2, with class 1 and class 2 showing major over-expressions or under-expressions respectively for 4 of the probes. These 4 probes belong to 2 genes and also belong to the group of 5 probes that were the most variable in "2nd-log obs/exp" (Figure 3B). The factors mentioned above were assessed for an eventual contribution to the variation in "2nd-log obs/exp" by comparing the numbers of factor variants in both classes and determining their probability by either a chi-square or Wilcoxon test. Since a comparison of the many variants in tissue specificity is not possible using this method, the mesodermic or endodermic origin of the tissues was used instead. The data in Table 4 demonstrate that with the exception of age (P = 3,64 × 10-6) none of these factors was significant, thereby suggesting that there is an increase in under-expression with age. The mean ages in classes 1 and 2 were 53,5 and 61,9 years respectively.


Epigenetic hereditary transcription profiles II, aging revisited.

Simons JW - Biol. Direct (2007)

Mean profiles of 2nd-log obs/exp for the two classes obtained with k-means clustering.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2265679&req=5

Figure 2: Mean profiles of 2nd-log obs/exp for the two classes obtained with k-means clustering.
Mentions: The remaining variation in "2nd-log obs/exp" could be due either to factors associated with nuclear programming, such as gender, age and tissue specificity or to other factors such as post-mortem changes (if the biopsy was obtained by autopsy), 'noise' in transcription or experimental error. Also individual specificity in the transcription profile is, in theory, possible and belongs with the first factor type. To determine the possible influence of such factors, the libraries were divided into 2 classes by k-means clustering. The mean "2nd log obs/exp", that indicate the deviations from expected transcription profiles, are depicted in Figure 2, with class 1 and class 2 showing major over-expressions or under-expressions respectively for 4 of the probes. These 4 probes belong to 2 genes and also belong to the group of 5 probes that were the most variable in "2nd-log obs/exp" (Figure 3B). The factors mentioned above were assessed for an eventual contribution to the variation in "2nd-log obs/exp" by comparing the numbers of factor variants in both classes and determining their probability by either a chi-square or Wilcoxon test. Since a comparison of the many variants in tissue specificity is not possible using this method, the mesodermic or endodermic origin of the tissues was used instead. The data in Table 4 demonstrate that with the exception of age (P = 3,64 × 10-6) none of these factors was significant, thereby suggesting that there is an increase in under-expression with age. The mean ages in classes 1 and 2 were 53,5 and 61,9 years respectively.

Bottom Line: The age-related index declined at a faster rate for males although it started from a higher level.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Toxicogenetics, MGC, Leiden University Medical Center, PO Box 9600, 2300, RC Leiden, The Netherlands. j.w.i.m.simons@lumc.nl

ABSTRACT

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.

Conclusion: 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.

Show MeSH
Related in: MedlinePlus