Abstract
Increasing evidence indicates that chronic inflammation and senescence are the cause of many severe age-related diseases, with both biological processes highly upregulated during aging. However, until now, it has remained unknown whether specific inflammation- or senescence-related genes exist that are common between different species or tissues. These potential markers of aging could help to identify possible targets for therapeutic interventions of aging-associated afflictions and might also deepen our understanding of the principal mechanisms of aging. With the objective of identifying such signatures of aging and tissue-specific aging markers, we analyzed a multitude of cross-sectional RNA-Seq data from four evolutionarily distinct species (human, mouse and two fish) and four different tissues (blood, brain, liver and skin). In at least three different species and three different tissues, we identified several genes that displayed similar expression patterns that might serve as potential aging markers. Additionally, we show that genes involved in aging-related processes tend to be tighter controlled in long-lived than in average-lived individuals. These observations hint at a general genetic level that affect an individual’s life span. Altogether, this descriptive study contributes to a better understanding of common aging signatures as well as tissue-specific aging patterns and supplies the basis for further investigative age-related studies.
Highlights
The phenomenon of biological aging is still far from satisfactorily explained due to its highly complex nature
Gene expression discriminates among tissues more strongly than ages To evaluate the homogeneity of the investigated transcriptomic data, we performed t-SNE dimensionality reduction of the RNA-Seq libraries based on the measured expression strengths of our 464 preselected senescence- and inflammation-associated genes
In the current descriptive study, we have investigated the inflammation- and senescence-related gene expression during aging in multiple tissues of four evolutionarily distinct species
Summary
The phenomenon of biological aging is still far from satisfactorily explained due to its highly complex nature. Aging is often described as a decline in cellular functions over time and the cause of several severe diseases, such as cardiovascular diseases, neurodegenerative diseases or cancer [1]. During an organism’s lifetime, most cells continuously undergo proliferation and cell division and reach the state of senescence at their own pace, when their telomeres have reached a certain shortening threshold. Over time, this process leads to an accumulation of senescent cells accompanied by loss of function and integrity of the respective tissues, which reflects the close connection of senescence with aging [3]. Cellular senescence was described as the “nexus of aging” by Bhatia-Dey et al, suggesting it as the main driver of the aging process [4]
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