Abstract Body: Arterial wall stiffness is the major risk factor for cardiovascular diseases. Due to lack of repeated clinical measurements throughout the lifespan of normal subjects, it is not clear whether organ specific effects of age-associated arterial stiffening alters human lifespan. Rodents, like humans, manifest arterial stiffening and decrease function as age progress. In this study, we measured vascular structure and function using vascular ultrasound in a cohort of 58 C57 male mice, beginning from 6 months of age until death, at every 3 months. Pulse wave velocity (PWV), a gold standard for arterial stiffness, was measured between right carotid artery and lower abdominal aorta. Fractional changes (FC) of lumen dimensions during a cardiac cycle, an index of arterial wall distensibility, were measured at carotid artery (CA-FC), thoracic aorta (TA-FC) and abdominal aorta (AB-FC). Average lifespan for this cohort was 24 months (ranged from 12 to 30 months). Mice exhibited a significant age-associated stiffing of arterial walls during the lifespan: PWV was increased in average by 16% (p<0.05); and CA-FC, TA-FC and AB-FC were reduced in average by 45%, 40% and 44%, respectively, (p<0.05). Interestingly, PWV at 6 months of age and its rate of change had strong negative correlations (r=0.82 and r=0.71) with the lifespan (Figure. A). Mice with slowest growth in PWV had the longest lifespan. Also, there were strong positive correlations between the rate of change of CA-FC (r=0.52), TA-FC (r=0.91) or AB-FC (r=0.96) and the lifespan (Figure. B). Mice with fastest decline in arterial wall distensibility had the shortest lifespan. Our data showed that arterial wall stiffness accelerated by age is an independent determinant of survival in mice.