Temporal Associations between T-Cell Senescence and Arterial Stiffness in Middle-Aged /Older Adults

TL;DR

This study explores how aging T-cells and stiff arteries are linked in older adults, finding possible bidirectional relationships.

Contribution

The study reveals bidirectional temporal associations between T-cell senescence and arterial stiffness in middle-aged and older adults.

Findings

Higher baseline p16 and p21 were nominally linked to increased arterial stiffness estimates.

BAK1 expression was associated with structural arterial stiffening.

Caloric restriction increased arterial stiffness only in those with high p16 at baseline.

Abstract

Age-related structural arterial remodeling (S) and load-dependent (LD) arterial stiffening can be calculated using arterial pulse-wave velocity (PWV) and blood pressure. Senescence-associated T-cells are cross-sectionally associated with both S-PWV and LD-PWV; however, the temporality isn’t known. This analysis aimed to determine whether higher T-cell senescence precedes or follows higher S-PWV and LD-PWV leveraging data from the VEGGIE trial. The VEGGIE trial was an 18-week randomized, controlled, caloric restriction weight-loss trial in middle-aged and older adults (age:57.6 ± 5.8 years, n = 58, systolic blood pressure=129±17mmHg at baseline). PWV was estimated (ePWV) using mean arterial pressure and age at each timepoint with previously established reference values. S-ePWV and LD-ePWV were calculated from total ePWV (T-ePWV) using participant-specific exponential models. CD3+ T-cell senescence gene expression (p16INK4a, p21CIP1/WAF1, BCL2, and BAK1) was measured. Multivariable linear regressions tested associations between baseline T-cell senescence and arterial stiffness with 18-week change in PWV or T-cell senescence. Models were adjusted for biologic sex, BMI, race, and treatment-group. Higher baseline p16 (β = 0.546,P=0.0688) and p21 (β = 0.398,P=0.0593) were nominally associated with increased T-ePWV. Higher baseline BAK1 was associated with increased S-ePWV (β = 0.0987,P=0.037). A treatment-group-by-baseline p16 interaction effect was observed with delta T-ePWV (p = 0.0234), where T-ePWV only increased in participants with high p16 at baseline in the caloric restriction group (β = 1.16,P=0.00405). Interestingly, higher baseline T-ePWV (β=-0.329,P=0.0556) and S-ePWV (β=-0.378,P=0.048) were associated with decreased p21. In conclusion, temporal associations between CD3+ senescence and arterial stiffness may be bi-directional and future research is needed directly measuring PWV and T-cell senescence over longer periods.