Transcriptional Signatures of Aging

Abstract

Genome-wide studies of aging have identified subsets of genes that show age-related changes in expression. Although the types of genes that are age-regulated vary among different tissues and organisms, some patterns emerge from these large data sets. First, aging is associated with a broad induction of stress response pathways, although the specific genes and pathways involved differ depending on cell type and species. In contrast, a wide variety of functional classes of genes are downregulated with age, often including tissue-specific genes. Whereas the upregulation of age-regulated genes is likely to be governed by stress-responsive transcription factors, questions remain as to why particular genes are susceptible to age-related transcriptional decline. Here, we discuss recent findings showing that splicing is misregulated with age. While defects in splicing could lead to changes in protein isoform levels, they could also impact gene expression through nonsense-mediated decay of intron-retained transcripts. The discovery that splicing is misregulated with age suggests that other aspects of gene expression, such as transcription elongation, termination and polyadenylation, must also be considered as potential mechanisms for age-related changes in transcript levels. Moreover, the considerable variation between genome-wide aging expression studies indicates that there is a critical need to analyze the transcriptional signatures of aging in single cell types rather than whole tissues. Since age-associated decreases in gene expression could contribute to a progressive decline in cellular function, understanding the mechanisms that determine the aging transcriptome provides a potential target to extend healthy cellular lifespan.

Proper splicing contributes to visual function in the aging Drosophila eye

“…We and others have identified correlations between reduced expression of splicing‐related genes and altered splicing patterns during aging (Stegeman & Weake, 2017). In Drosophila cells, splicing factors act combinatorially to regulate splicing events and more than half of splicing events are regulated by more than one splicing factor (Brooks et al, 2015).…”

“…Recent studies show that changes in splicing are part of the transcriptional signature of aging cells (Deschênes & Chabot, 2017; Stegeman & Weake, 2017). Age‐associated changes in alternative splicing have been observed in human brain and in mouse skin, skeletal muscle, bone, thymus, and white adipose tissue (Rodríguez et al, 2016; Tollervey et al, 2011).…”

“…We previously showed that the altered gene expression profile of aging photoreceptors correlates with a decline in visual behavior, termed visual senescence (Carbone et al, 2016; Hall et al, 2017). As other transcriptome studies have also shown a correlation between splicing factor expression and splicing during aging (Stegeman & Weake, 2017), we wondered whether age‐associated alterations in splicing could contribute to visual senescence in flies. To examine this question, we sought to characterize the contribution of individual age‐regulated splicing factors to age‐associated changes in alternative splicing and visual function in the Drosophila eye.…”

Comprehensive transcriptome profiling in elderly cancer patients reveals aging‐altered immune cells and immune checkpoints

“…Although much effort was made to study why aging causes cancer, less attention was paid to the unique features of cancer in elderly patients. Several previous studies have revealed some transcriptomics signatures of aging in different tissues . For example, genes involved in stress response and DNA repair were upregulated in aged brain .…”

“…Several previous studies have revealed some transcriptomics signatures of aging in different tissues. 4 For example, genes involved in stress response and DNA repair were upregulated in aged brain. 5 In kidney, aging-associated genes involve in cellular matrix and cellular polarity.…”