Investigation of the roles of aging and caloric restriction on arterial biomechanics

Aging significantly contributes to the onset of cardiovascular diseases. The structural and functional alterations such as stiffening of arteries, vascular remodeling, and dysfunction of endothelium are associated with aging. The purpose of this thesis was to investigate the impacts of aging and different types of caloric restriction (CR) on arterial biomechanics. In this research, 10-week-old male C57/BL6 mice were divided into 3 groups: Ad libitum (AL), chronic caloric restriction (CCR; 25% of food restriction of AL group) and intermittent CR (ICR; 3 weeks of 50% food restriction (ICR-R) followed by AL feeding for 3 weeks (ICR- RF)) and fed until 85 weeks of mouse age. After overnight fasting of animals, mesenteric resistance arteries (MRAs) were isolated from 10 (young), 46/49 (middle age), and 82/85(old) weeks old animals. Vascular reactivity, passive, active and endothelium- dependent responses were assessed by using wire myography. In addition, immunofluorescence (IF) was performed to visualize and quantify elastin, collagen IV and desmin proteins in the MRAs. The internal diameter and arterial stiffness were significantly increased with aging in 82/85-week-old AL group compared to 10-week-old group. Internal diameters were 236.8±10.85 μm and 313±10.3 μm at 10-week-old and 82/85-week-old mice in AL group, respectively (p<0.05). Arterial stiffness indexes were 13.8±0.77 mN/mm and 17.3±1.11 mN/mm at 10-week-old and 82/85-week-old mice in AL group, respectively. But internal diameter and arterial stiffness were not changed with ageing in CCR group. On the other hand, internal diameter (336±19.03 μm) and arterial stiffness index (19±1.8 mN/mm) were significantly increased with aging in 82-week-old ICR-R group of mice compared to 10-week-old mice (p<0.05). In conclusion, lifelong CCR prevented outward hypertrophic remodeling and age associated arterial stiffness of MRAs in 82/85-week-old male mice. In addition, only three weeks of AL feeding after three weeks of 50 % CR application mitigated the vascular aging effects. These results demonstrate that the beneficial effects of CR in CVD could be via vascular remodeling mechanisms, specifically modulating arterial lumen diameter and stiffness.