Caveolin-1 knock-out (KO) mice have a shorter life-span than wild-type (WT) mice (Park et al., 2003). Caveolae, and caveolin-1, can modulate vascular function while normal ageing has been associated with changes in structure and function of resistance arteries. We examined the effect of caveolin-1 ablation on vascular ageing. Wild type (WT) and caveolin-1 knockout (KO) mice were killed by cervical dislocation at 3 and 12 months of age (3m, 12m). Third order mesenteric arteries were dissected, mounted on a pressure myograph (60mmHg, superfused with physiological salt solution (PSS), 95% air/5% CO₂, 37°C) and contractile responses to noradrenaline (NA) (10^-9-10^-5M) and KPSS (100mM) examined. Passive pressure-diameter/wall thickness relationships (5-140 mmHg) were determined in the absence of calcium and further calculations performed (Schofield et al., 2002) (n=30 3m WT, n=36 3m KO, n=23 12m WT, n=17 12m KO). Data is expressed as maximal responses (mean ± SEM) with statistical differences (p<0.05) examined by ANOVA and Bonferroni. Caveolin-1 ablation significantly reduced NA constriction of vessels from 3 month mice (69 ± 2% KO (n=24); 81 ± 1% WT (n=30)). Ageing significantly reduced constriction in WT arteries (66 ± 2% 12m n=24), but had no effect on KO vessels (68 ± 2% 12m n=19). Constriction of arteries from 12 month WT and 3 and 12 month KO mice was comparable. Similar changes were observed with KPSS; while ageing in the WT mouse reduced constriction (72 ± 3% (3m, n=20) to 53 ± 4% (12m, n=19). Responses in KO mice at 3m were reduced c.f. WT (51 ± 3% n=29) but there were no further significant age-related changes (39 ± 4% n=19). Ageing was associated with increased diameter and decreased wall: lumen ratio in arteries from WT and KO mice. However, the wall thickness and cross sectional area of KO mice were increased c.f. WT vessels indicating growth (growth index = ((CSA₁-CSA₂)/CSA₂ )*100; 43% 3m; 21% 12m). Vessel distensibility was reduced by ageing in WT mice as shown by a leftward shift in stress-strain curves. Distensibility was also reduced in vessels from 3 month KO mice, however, these vessels were resistant to any further age-related changes. Thus caveolin-1 ablation causes structural and functional changes in resistance arteries which are not altered by ageing. This suggests that caveolae play an important role in the normal vascular ageing process.