The prediction of risk to the patient in ascending thoracic aortic aneurysm (ATAA) is a significant challenge and the subject of much active research. In the present work, a combination of mouse model experiments and computer simulations was used to explore potential biomarkers that correlate with mouse lifespan, used as a surrogate for risk of a catastrophic event. Image-based, mouse-specific fluid-structure-interaction models were developed for
Fbln4
SMKO
mice (n = 10) at ages two and six months. The results of the simulations were used to quantify potential biofluidic biomarkers, complementing the geometrical biomarkers obtained directly from the images. Comparing the different geometrical and biofluidic biomarkers to the mouse lifespan, it was found that mean oscillatory shear index (OSI
mean
) and minimum time-averaged wall shear stress (TAWSS
min
) at six months showed the largest correlation with lifespan (r
2
= 0.70, 0.56), with both correlations being positive (i.e., mice with high OSI
mean
and high TAWSS
min
tended to live longer). When change between two and six months was considered, the change in TAWSS
min
showed a much stronger correlation than OSI
mean
(r
2
= 0.75 vs. 0.24), and the correlation was negative (i.e., mice with increasing TAWSS
min
over this period tended to live less long). The results highlight potential biomarkers of ATAA outcomes that can be obtained through noninvasive imaging and computational simulations.