The Effect of Caloric Restriction on the Aortic Tissue of Aging Rats

Abstract

Connective tissue shows peculiar and complex age-related modifications, which can be, at least in part, responsible for altered functions and increased susceptibility to diseases. Food restriction has long been known to prolong life in rodents, having antiaging effects on a variety of physiologic and pathologic processes. Therefore, the aorta has been investigated in rats fed normal or hypocaloric diet, from weaning to senescence. Compared with controls, caloric-restricted animals showed less pronounced age-dependent alterations such as elastic fiber degradation, collagen accumulation and cellular modifications. Immunocytochemical analyses revealed that elastic fibers were positively labelled for biglycan, decorin, ApoB100 (LDL), ApoA1 (HDL) and elastase and that the intensity of the reactions was time- and diet-dependent. With age, the major changes affecting aortic elastic fibers were increased positivity for decorin, LDL and elastase. Compared with age-matched normal fed rats, caloric restricted animals revealed lower content of LDL, decorin and elastase and higher positivity for HDL. These data suggest that a caloric restricted diet might influence the aging process of the arterial wall in rats, delaying the appearance of age-related degenerative features, such as structural alterations of cells and matrix and modified interactions of elastin with cells and with other extracellular matrix molecules.

Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice

“…Interestingly, NMN also induced a partial restoration of aortic elastin to levels not significantly different from young control animals. We have not previously observed an increase in aortic elastin with any other late‐life lifestyle or pharmacological intervention in mice (Fleenor et al ., 2010, 2012a,b), although lifelong CR protects against the loss of elastic properties within the arteries, including elastin degradation (Fornieri et al ., 1999; Donato et al ., 2013). Thus, it is possible that NMN may partially restore the loss of arterial elastin by mimicking the effects of CR, although further studies would be needed to provide direct support for this mechanism.…”

Caloric restriction: powerful protection for the aging heart and vasculature

“…In older rats, CR resulted in less arterial stiffness compared with free-fed rats, as evidenced by greater fractional expansion of the aorta during the cardiac cycle (i.e., arterial distensibility) and slower pulse wave velocity (2). These effects of CR are accompanied by less fibrous matrix (i.e., collagen) accumulation, more elastin, and better preservation of vascular smooth muscle (2,68). Furthermore, CR appears to prevent age-related vascular accumulation of the proteoglycan decorin (68), which has been shown to promote vascular fibrosis and mineralization through the activation of TGF-␤ (158,212).…”

“…These effects of CR are accompanied by less fibrous matrix (i.e., collagen) accumulation, more elastin, and better preservation of vascular smooth muscle (2,68). Furthermore, CR appears to prevent age-related vascular accumulation of the proteoglycan decorin (68), which has been shown to promote vascular fibrosis and mineralization through the activation of TGF-␤ (158,212). Less arterial stiffness has also been shown in arteries isolated from spontaneously hypertensive rats exposed to short-term CR (i.e., 5 wk) (53).…”

Aging and Atherosclerosis

“…165 In particular, caloric restriction (CR) is a common method to manipulate diet and the beneficial effects of CR on vessel aging have been proven in animal models, 166 -168 including preservation of matrix components within the vessel wall, 169 improving EC function through augmenting NO generation, 170 reducing sensitivity to oxLDL, 171 reducing oxidative stress by upregulating antioxidants and protecting mitochondria function, 170,172 and inhibiting inflammation. 173 Although CR may be inappropriate in many patients, drugs and dietary supplements that mimic CR effects without affecting nutritional balance may offer a wider therapeutic option.…”