Background and Aim: 

The immune system undergoes profound transformations with aging, marked by an accumulation of exhausted T-cells and chronic low-grade inflammation. Immune-inflammatory phenomena have been implicated in the pathogenesis of several cardiovascular diseases, but it remains unclear how the aging immune system interplays with cardiovascular risk factors. We aim to describe a baseline of the process of physiological immune aging in a thoroughly phenotyped, strictly-healthy cohort compared to a cohort presenting cardiovascular risk factors to identify how this interactions takes place.

Methods:

We employed multicolour flow cytometry to comprehensively phenotype the peripheral blood T-cell compartment of 350 healthy subjects stratified by gender and age ranging from 30-79 years old (available within the STAAB study). Building on a comprehensive clinical phenotyping available, we were able to precisely define the “strictly-healthy” sample (n=350) based on the absence of comorbidities and risk factors including smoking and obesity and inconspicuous results of oral glucose test and echocardiography. The immune-aging profile of strictly healthy subjects was then compared with age-matched subjects (n=60) presenting at least three canonical cardiovascular risk factors, i.e. hypertension, dyslipidemia, and hyperglyceamia. 

Results: 

We observed a linear age-dependent increase in the intracellular expression of pro-inflammatory cytokines including interferon-γ and TNF, and an increase of terminally differentiated CD8+ cells. Using a dimensionality reduction approach allowed to classify the aging immune system into four main phenotypic states, characterized by T-cell differentiation and cytokine production. Across these phenotypic states, age-dependent shifts in the immune aging profile distribution became apparent that were more pronounced in healthy men compared to healthy women thus revealing a dimorphism in the healthily aging immune system. Further, healthy men showed a significantly different distribution of the T-cell phenotypic states compared to age-matched groups of men presenting with classical cardiovascular risk factors. 

Conclusion: 

To the best of our knowledge, these findings provide the first description of immunosenescence profiling in a “strictly healthy” population and show how they interplay with lifestyle and cardiovascular risk factors. Future studies may further address whether immune profiling could offer additional diagnostic/ prognostic value for patients at higher cardiovascular risk.