The following is the summary of “Association between age and the host response in critically ill patients with sepsis” published in the December 2022 issue of Critical care by Michels, et al.

An increased risk of dying from sepsis is linked to getting older. However, existing studies on the impact of age on host response aberrations are mostly limited to plasma cytokine levels, ignoring key pathophysiology sepsis areas like endothelial cell activation and function and coagulation activation. The major reason for conducting this research was to learn how age is linked to abnormalities in the blood transcriptomes of sepsis patients. Researchers analyzed the clinical outcome of sepsis patients stratified by age decades (n=1,952), 16 plasma biomarkers offering insight into dysregulation of distinct pathophysiological domains (n = 899), and blood leukocyte transcriptomes (n=488). 

The results of a blood transcriptome study comparing patients with sepsis and healthy controls were confirmed in a separate cohort. Regardless of coexisting conditions or degree of sickness, advanced age was associated with a higher risk of dying. Despite increased disease severity scores, aging was linked to reduced endothelial cell activation and dysfunction and comparable activation of inflammation and coagulation. Patients above the age of ≥ 70 had lower expression of genes involved in cytokine signaling and innate and adaptive immunity in their blood leukocytes, while patients under 50 had higher expression of these genes. 

Since healthy subjects over the age of ( ≥70) demonstrated higher expression of gene pathways associated with innate immunity and cytokine signaling compared to healthy individuals under the age of less than 50, the decreased expression of these pathways in subjects  (≥70) years was sepsis-induced. This is the first study to show that endothelial cell activation and dysfunction caused by sepsis are attenuated with age and that a blood leukocyte transcriptome profile indicates decreased innate immune and cytokine signaling in older adults. These findings highlight the importance of considering age when selecting patients for future sepsis trials focusing on the immunological and/or endothelial cell response.

Source: ccforum.biomedcentral.com/articles/10.1186/s13054-022-04266-9