Correlations with Mortality in Levels of Proteins Secreted by Senescent Cells

Here, researchers investigate correlations between late life mortality and levels of specific proteins produced by senescent cells as a part of the senescence-associated secretory phenotype (SASP). While looking over the paper, it is worth bearing in mind that circulating levels of many of the molecules thought to be important components of the SASP do not appear to correlate well with senescent cell burden. Why this is the case remains to be understood on a molecule by molecule basis, but note that many of the SASP molecules are widely used for signaling by other cell types and in other circumstances.

A robust and heterogenous secretory phenotype is a core feature of most senescent cells. In addition to mediators of age-related pathology, components of the senescence associated secretory phenotype (SASP) have been studied as biomarkers of senescent cell burden and, in turn, biological age. Therefore, we hypothesized that circulating concentrations of candidate senescence biomarkers, including chemokines, cytokines, matrix remodeling proteins, and growth factors, could predict mortality in older adults.

We assessed associations between plasma levels of 28 SASP proteins and risk of mortality over a median follow-up of 6.3 years in 1,923 patients 65 years of age or older with zero or one chronic condition at baseline. Overall, the five senescence biomarkers most strongly associated with an increased risk of death were GDF15, RAGE, VEGFA, PARC, and MMP2, after adjusting for age, sex, race, and the presence of one chronic condition. The combination of biomarkers and clinical and demographic covariates exhibited a significantly higher c-statistic for risk of death (0.79) than the covariates alone (0.70). Collectively, these findings lend further support to biomarkers of cellular senescence as informative predictors of clinically important health outcomes in older adults, including death.


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