Accelerated aging-related transcriptome changes in the female prefrontal cortex

Yuan, Yuan
Chen, Yi-Ping Phoebe
Boyd-Kirkup, Jerome
Khaitovich, Philipp
Somel, Mehmet
Human female life expectancy is higher than that of males. Intriguingly, it has been reported that women display faster rates of age-related cognitive decline and a higher prevalence of Alzheimers disease (AD). To assess the molecular bases of these contradictory trends, we analyzed differences in expression changes with age between adult males and females, in four brain regions. In the superior frontal gyrus (SFG), a part of the prefrontal cortex, we observed manifest differences between the two sexes in the timing of age-related changes, that is, sexual heterochrony. Intriguingly, age-related expression changes predominantly occurred earlier, or at a faster pace, in females compared to men. These changes included decreased energy production and neural function and up-regulation of the immune response, all major features of brain aging. Furthermore, we found that accelerated expression changes in the female SFG correlated with expression changes observed in AD, as well as stress effects in the frontal cortex. Accelerated aging-related changes in the female SFG transcriptome may provide a link between a higher stress exposure or sensitivity in women and the higher prevalence of AD.


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Aging is a complex process that causes decline in organisms’ reproductive capacity and chance of survival. Even though aging tends to reduce fitness, it is not eliminated by natural selection and is observed in many multicellular species, and this leads to an evolutionary paradox. The mutation accumulation theory states that due to the declining force of natural selection with age, old-age-expressed deleterious mutations will not be effectively eliminated, and can contribute to the aging phenotype. A limite...
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Citation Formats
Y. Yuan, Y.-P. P. Chen, J. Boyd-Kirkup, P. Khaitovich, and M. Somel, “Accelerated aging-related transcriptome changes in the female prefrontal cortex,” AGING CELL, pp. 894–901, 2012, Accessed: 00, 2020. [Online]. Available: