Functional status is considered the main determinant of healthy aging. Impairment in skeletal muscle and the cardiovascular system, two interrelated systems, results in compromised functional status in aging. Increased oxidative stress and inflammation in older subjects constitute the background for skeletal muscle and cardiovascular system alterations. Aged skeletal muscle mass and strength impairment is related to anabolic resistance, mitochondrial dysfunction, increased oxidative stress and inflammation as well as a reduced antioxidant response and myokine profile. Arterial stiffness and endothelial function stand out as the main cardiovascular alterations related to aging, where increased systemic and vascular oxidative stress and inflammation play a key role. Physical activity and exercise training arise as modifiable determinants of functional outcomes in older persons. Exercise enhances antioxidant response, decreases age-related oxidative stress and pro-inflammatory signals, and promotes the activation of anabolic and mitochondrial biogenesis pathways in skeletal muscle. Additionally, exercise improves endothelial function and arterial stiffness by reducing inflammatory and oxidative damage signaling in vascular tissue together with an increase in antioxidant enzymes and nitric oxide availability, globally promoting functional performance and healthy aging. This review focuses on the role of oxidative stress and inflammation in aged musculoskeletal and vascular systems and how physical activity/exercise influences functional status in the elderly.

Background: Insulin resistance (IR) is frequently associated with endothelial dysfunction and has been proposed to play a major role in cardiovascular disease (CVD). On the other hand, obesity has long been related to IR and increased CVD. However it is not known if IR is a necessary condition for endothelial dysfunction in human obesity, allowing for preserved endothelial function in obese people when absent. Therefore, the purpose of the study was to assess the relationship between IR and endothelial dysfunction in human obesity and the mechanisms involved. Methods: Twenty non-insulin resistant morbid obese (NIR-MO), 32 insulin resistant morbid obese (IR-MO), and 12 healthy subjects were included. Serum concentrations of glucose, insulin, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), resistin and adiponectin were determined. IR was evaluated by HOMA-index. Endothelium-dependent relaxation to bradykinin (BK) in mesenteric microvessels was assessed in wire myograph. Results: Serum IL-6, and TNF-α levels were elevated only in IR-MO patients while resistin was elevated and adiponectin reduced in all MO individuals. Mesenteric arteries from IR-MO, but not from NIR-MO subjects displayed blunted relaxation to BK. Vasodilatation was improved in IR-MO arteries by the superoxide scavenger, superoxide dismutase (SOD) or the mitochondrial-targeted SOD mimetic, mito-TEMPO. NADPH oxidase inhibitors (apocynin and VAS2870) and the nitric oxide synthase (NOS) cofactor, tetrahydrobiopterin failed to modify BK-induced vasodilatations. Superoxide generation was higher in vessels from IR-MO subjects and reduced by mito-TEMPO. Blockade of TNF-α with infliximab, but not inhibition of inducible NOS or cyclooxygenase, improved endothelial relaxation and decreased superoxide formation. Conclusions: Endothelial dysfunction is observed in human morbid obesity only when insulin resistance is present. Mechanisms involved include augmented mitochondrial superoxide generation, and increased systemic inflammation mediated by TNF-α. These findings may explain the different vascular risk of healthy vs unhealthy obesity.

Introduction: Novel effective therapeutic strategies are necessary for treating erectile dysfunction secondary to cavernous nerve injury (CNI). Aim: To functionally evaluate the benefits of long-term oral treatment with a phosphodiesterase type 5 inhibitor on the potential capacity of intracavernosal cell therapy to recover erectile function after CNI. Methods: Bilateral crush CNI (BCNI) was produced in anesthetized male rats. After BCNI, rats were treated with the phosphodiesterase type 5 inhibitor tadalafil (TAD; 5 mg/kg/d orally; BCNI + TAD), a single intracavernosal injection of bone marrow–derived mesenchymal stem cells (BMSCs; BCNI + BMSC), or dual therapy (BCNI + BMSC + TAD). Ex vivo function of the corpus cavernosum (CC) and in vivo intracavernosal pressure responses to CN electrical stimulation were evaluated 4 weeks after BCNI. Trichrome staining and terminal 2′-deoxyuridine-5′-triphosphate nick-end labeling assay were used for fibrosis and apoptosis determination, respectively, in the CC. Main Outcome Measures: In vivo erectile responses in anesthetized rats, ex vivo evaluation of endothelium-dependent relaxation, neurogenic relaxation and neurogenic contraction in CC strips, and histologic evaluation of fibrosis and apoptosis in cavernosal tissue. Results: BCNI resulted in a marked decrease of erectile responses that were partly recovered in the BCNI + TAD and BCNI + BMSC groups. Complete recovery of erectile function was achieved only in the BCNI + BMSC + TAD group. Endothelium-dependent and nitric oxide donor-induced relaxations of the CC were not altered by BCNI or the treatments. BCNI resulted in enhanced neurogenic adrenergic contractions and impaired nitrergic relaxations of the CC. The BCNI + TAD group displayed diminished neurogenic contractions, whereas the BCNI + TAD and BCNI + BMSC groups showed partly recovered nitrergic responses. In the BCNI + BMSC + TAD group, neurogenic contractions were decreased and nitrergic relaxations were normalized. Cavernosal apoptosis and fibrosis were similarly prevented in the BCNI + TAD, BCNI + BMSC, and BCNI + BMSC + TAD groups. Conclusion: A dual strategy combining the intracavernosal injection of BMSCs and oral administration of TAD was superior to individual approaches in normalizing neurogenic control of cavernosal tone and preserving erectile function after CNI, suggesting the potential of this dual strategy in the future management of erectile dysfunction after radical prostatectomy.

The aim of the present study was to examine the effects of onion as functional ingredient on the oxidative status, lipoprotein levels (total cholesterol-TC, HDL-C, LDL-C), triacylglycerides (TAG) and vascular reactivity of mesenteric arteries in hypercholesterolemic Wistar rats. Twenty-four animals were fed with three different diets [control, high-cholesterol diet (HC) and high-cholesterol enriched with onion diet (HCO)]. After seven weeks of experimental feeding the rats were euthanized for blood and tissues collection. TC, HDL-C, LDL-C and TAG were measured, and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS•+) scavenging capacity and ferric reducing antioxidant power (FRAP) were determined in plasma. Superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzyme activities were assayed in erythrocyte lysates. Endothelium-dependent vasodilation to acetylcholine was evaluated in mesenteric arterial segments. NADPH oxidase (NOX) was also measured by lucigenin-derived chemiluminiscence. The dietary cholesterol content significantly affected plasma lipoprotein levels, increased superoxide generation from NOX, and caused impaired endothelium-dependent vasodilation in the rat mesenteric arteries. Onion ingredient improved antioxidant status in HCO group, as it was evidenced by ABTS•+ and FRAP values and SOD and GPx enzyme activities compared to the HC-fed group, reduced the increment in NOX activity and reversed endothelial dysfunction promoted by the HC diet. Scavenging of superoxide with TEMPOL or inhibition of NOX with apocynin improved endothelium-dependent vasodilation only in HC-fed rats. Enrichment of diet with onion as functional ingredient could be proposed as a complementary approach to prevent or partially modulate vascular dysfunction, reducing some of the risk indexes linked to initial development of atherosclerosis.