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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

Deviation index (= standard deviation of all "2nd-log obs/exp's" in a library) decreases with age (P = 0,012). Correlation coefficient is 0,32.
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Figure 7: Deviation index (= standard deviation of all "2nd-log obs/exp's" in a library) decreases with age (P = 0,012). Correlation coefficient is 0,32.

Mentions: To analyse the observed decrease in standard deviation (Fig. 3B) the relationship between age and the 'deviation index' was assessed. The 'deviation index' represents the standard deviation of all "2nd-log obs/exp" in a given library and indicates the extent to which the transcription profile of that library deviates from the mean standard transcription profile. It has previously been shown that this index is significantly enhanced in cancer tissues [2]. If the aging process results from the increasing accumulation of mutational damage one would expect to observe a parallel increase in the deviation index during aging. The opposite, however, appears to be the case, since the regression of age with the deviation index of "2nd-log obs/exp" (Figure. 7) shows that the deviation index decreases significantly with increasing age (P = 0,0117). This decrease might suggest that during aging, transcription becomes more accurate and/or less variable.


Epigenetic hereditary transcription profiles II, aging revisited.

Simons JW - Biol. Direct (2007)

Deviation index (= standard deviation of all "2nd-log obs/exp's" in a library) decreases with age (P = 0,012). Correlation coefficient is 0,32.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 7: Deviation index (= standard deviation of all "2nd-log obs/exp's" in a library) decreases with age (P = 0,012). Correlation coefficient is 0,32.
Mentions: To analyse the observed decrease in standard deviation (Fig. 3B) the relationship between age and the 'deviation index' was assessed. The 'deviation index' represents the standard deviation of all "2nd-log obs/exp" in a given library and indicates the extent to which the transcription profile of that library deviates from the mean standard transcription profile. It has previously been shown that this index is significantly enhanced in cancer tissues [2]. If the aging process results from the increasing accumulation of mutational damage one would expect to observe a parallel increase in the deviation index during aging. The opposite, however, appears to be the case, since the regression of age with the deviation index of "2nd-log obs/exp" (Figure. 7) shows that the deviation index decreases significantly with increasing age (P = 0,0117). This decrease might suggest that during aging, transcription becomes more accurate and/or less variable.

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