Abstract
The prefrontal cortex (PFC) is one of the brain regions with more prominent changes in human aging. The molecular processes related to the cognitive decline and mood changes during aging are not completely understood. To improve our knowledge, we integrated transcriptomic data of four studies of human PFC from elderly people (58–80 years old) compared with younger people (20–40 years old) using a meta-analytic approximation combined with molecular signature analysis. We identified 1817 differentially expressed genes, 561 up-regulated and 1256 down-regulated. Pathway analysis revealed down-regulation of synaptic genes with conservation of gene expression of other neuronal regions. Additionally, we identified up-regulation of markers of astrogliosis with transcriptomic signature compatible with A1 neurotoxic astrocytes and A2 neuroprotective astrocytes. Response to interferon is related to A1 astrocytes and the A2 phenotype is mediated in aging by activation of sonic hedgehog (SHH) pathway and up-regulation of metallothioneins I and genes of the family ERM (ezrin, radixin, and moesin). The main conclusions of our study are the confirmation of a global dysfunction of the synapses in the aged PFC and the evidence of opposite phenotypes of astrogliosis in the aging brain, which we report for the first time in the present article.
Highlights
Aging is the physiological and morphological decline of individuals with the passing of time, which increases their susceptibility to diseases such as cancer, diabetes, neurodegenerative and cardiovascular disorders, and increases their vulnerability to death
Meta-analysis of transcriptomic data increases the statistical power of the individual datasets and, in addition, can identify differentially expressed genes (DEGs) that are consistently de-regulated across the different experiments
We detected that neurons are some of the most important cells affected by aging in the prefrontal cortex (PFC), and, in accordance with other researchers, we delineated the biggest impairment to be in synapse function, with specific variations depending on the type of synapses
Summary
Aging is the physiological and morphological decline of individuals with the passing of time, which increases their susceptibility to diseases such as cancer, diabetes, neurodegenerative and cardiovascular disorders, and increases their vulnerability to death. It has become a public health problem since life expectancy has increased, with a consequent world population aging [1]. The prefrontal cortex (PFC) seems to be morphologically and functionally more vulnerable to the effects of aging compared with others areas [3]. In astrocytes there has been reported an increase of the activation with aging.
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