MicroRNA, mRNA, and protein expression link development and aging in human and macaque

Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Genome Research (Impact Factor: 14.63). 09/2010; 20(9):1207-18. DOI: 10.1101/gr.106849.110
Source: PubMed


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.

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    • "In the only study of this kind of which we are aware, Somel et al. (2010)) were able to map parallel developmental and aging changes in microRNAs (miRs) and messenger RNAs (mRNAs) in gross samples of the surface-accessible superior frontal gyrus from frozen postmortem brains of healthy Rhesus macaque, and in the same region which had been dissected from frozen healthy human brains obtained from an NICHD/NIH-sponsored repository of frozen human brains. Relevantly, the major changes in gene expression in NHP and human superior frontal gyrus coordinately change with age when differences in lifespan are taken into account (Somel et al., 2010). However, it is not known to what extent other parts of the brain parallel these findings, including components of the fronto-limbic circuit, Furthermore, inasmuch as most repositories of diseased and control human brains are often available only in an intact, frozen state, it is a challenge to access and isolate centrally located brain regions. "
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    • "Analysis of the expression level of miR-34a in the PM control samples revealed a pronounced postnatal increase in expression that plateaus after the teenage years. Age-dependent elevation of miR-34a expression in brain and cardiac tissue has previously been reported (Somel et al. 2010; Li et al. 2011; Boon et al. 2013). Since our pediatric subjects are within the timeframe of rapid increase in miR-34a expression, it is imperative that we consider subject age when investigating microRNA expression events in this population. "
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    • "Metabolite trajectories were gradual and continuous starting from early adulthood, with very few signals showing mid-life reversals. These results are generally consistent with the observations from the studies on transcript and protein profiles across diverse aging populations (Zou et al., 2000; Pletcher et al., 2002; Somel et al., 2010). Indeed, our analysis of age-associated gene expression involving both control and dietary restricted long-lived individuals indicates that metabolites and transcripts exhibit nearly identical frequencies of dietdependent to diet-independent effects. "
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