MicroRNA, mRNA, and protein expression link development and aging in human and macaque brain.
Changes in gene expression levels determine differentiation of tissues involved in development and are associated with functional decline in aging. Although development is tightly regulated, the transition between development and aging, as well as regulation of post-developmental changes, are not well understood. Here, we measured messenger RNA (mRNA), microRNA (miRNA), and protein expression in the prefrontal cortex of humans and rhesus macaques over the species' life spans. We find that few gene expression changes are unique to aging. Instead, the vast majority of miRNA and gene expression changes that occur in aging represent reversals or extensions of developmental patterns. Surprisingly, many gene expression changes previously attributed to aging, such as down-regulation of neural genes, initiate in early childhood. Our results indicate that miRNA and transcription factors regulate not only developmental but also post-developmental expression changes, with a number of regulatory processes continuing throughout the entire life span. Differential evolutionary conservation of the corresponding genomic regions implies that these regulatory processes, although beneficial in development, might be detrimental in aging. These results suggest a direct link between developmental regulation and expression changes taking place in aging.
Somel
Mehmet
M
Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China. somel@eva.mpg.de
Guo
Song
S
Fu
Ning
N
Yan
Zheng
Z
Hu
Hai Yang
HY
Xu
Ying
Y
Yuan
Yuan
Y
Ning
Zhibin
Z
Hu
Yuhui
Y
Menzel
Corinna
C
Hu
Hao
H
Lachmann
Michael
M
Zeng
Rong
R
Chen
Wei
W
Khaitovich
Philipp
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D000818:Animals; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D019143:Evolution, Molecular; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008251:Macaca; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D011506:Proteins / Q000378:metabolism*; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*
D035683:MicroRNAs; D011506:Proteins; D012333:RNA, Messenger