How our protective systems turn against us during aging.

Differentially expressed genes during tissue aging and associated biological processes. The upper part shows the number of identified differentially expressed genes (DEGs) within all three age comparisons (early aging, late aging, longevity) in every investigated species and tissue. The lower part shows for every comparison the dominant biological processes as determined by the majority of the annotated functions of the respective DEGs. Note that in some comparisons only few DEGs could be identified and hence may only poorly reflect the underlying age-related processes (n.d. – no data).

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. Because aging is incompletely understood, a decades-old and still ongoing debate exists on the true source of aging, giving rise to a variety of competing theories. Senescence and inflammatory processes are two of the most common themes within these discussions of the molecular driving forces of aging. Cellular senescence is a state in which permanent replication is halted, and thus cells are unable to further proliferate, and their overall function is strongly diminished. Senescence is meant to be a protective mechanism, stopping further proliferation if cells are on the verge to turn into malignant tumor cell due to severe DNA damage, for example because of telomere shortening. 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.

Another systemic process, that is observed in most tissues with age is the increased release of proinflammatory messenger substances. As a consequence, low-grade chronic inflammatory processes slowly but irresistibly begin to damage organs and are viewed as the cause of other age-related chronic diseases, such as Alzheimer’s disease, osteoporosis or diabetes. This state of chronic age-dependent inflammation is also suspected as one of the main causes of biological aging and was described as “inflammaging”. Miquel et al. proposed an integrative oxidation-inflammation theory of aging, arguing that chronic oxidative stress originating from mitochondria leads to senescence in cells of the regulatory systems, such as the immune system. Unarguably, senescence and inflammation processes are strongly connected and contribute to an organism’s aging phenotype as well as its rate of aging. Therefore, understanding how those systemic processes are regulated during aging in different species and tissues could supply many answers related to biological aging itself.

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). We describe our results in a recent paper published by the journal Aging (https://www.aging-us.com/article/102345/text).

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.

  • [DOI] E. Barth, A. Srivastava, M. Stojiljkovic, C. Frahm, H. Axer, O. W. Witte, and M. Marz, “Conserved aging-related signatures of senescence and inflammation in different tissues and species.,” Aging, vol. 11, 2019.
    [Bibtex]
    @Article{Barth:19,
    author = {Barth, Emanuel and Srivastava, Akash and Stojiljkovic, Milan and Frahm, Christiane and Axer, Hubertus and Witte, Otto W and Marz, Manja},
    title = {Conserved aging-related signatures of senescence and inflammation in different tissues and species.},
    journal = {Aging},
    year = {2019},
    volume = {11},
    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.},
    doi = {10.18632/aging.102345},
    keywords = {RNA-Seq; aging; inflammaging; senescence; transcriptomics},
    pmid = {31606727},
    }

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