Key points
The development of age‐related arterial endothelial dysfunction, a key antecedent of increased cardiovascular disease (CVD) risk, is mediated largely by reduced nitric oxide ...bioavailability as a consequence of oxidative stress.
Mitochondria are critical signalling organelles in the vasculature, which, when dysregulated, become a source of excessive reactive oxygen species; the role of mitochondria‐derived oxidative stress in age‐related vascular dysfunction is unknown.
We show that a mitochondria‐targeted antioxidant, MitoQ, ameliorates vascular endothelial dysfunction in old mice and that these improvements are associated with the normalization of mitochondria‐derived oxidative stress and markers of arterial mitochondrial health.
These results indicate that mitochondria‐derived oxidative stress is an important mechanism underlying the development of age‐related vascular endothelial dysfunction and therefore may be a promising therapeutic target.
Mitochondria‐targeted antioxidants represent a novel strategy for preserving healthy vascular endothelial function in primary ageing and preventing age‐related CVD in humans.
Age‐related arterial endothelial dysfunction, a key antecedent of the development of cardiovascular disease (CVD), is largely caused by a reduction in nitric oxide (NO) bioavailability as a consequence of oxidative stress. Mitochondria are a major source and target of vascular oxidative stress when dysregulated. Mitochondrial dysregulation is associated with primary ageing, but its role in age‐related endothelial dysfunction is unknown. Our aim was to determine the efficacy of a mitochondria‐targeted antioxidant, MitoQ, in ameliorating vascular endothelial dysfunction in old mice. Ex vivo carotid artery endothelium‐dependent dilation (EDD) to increasing doses of acetylcholine was impaired by ∼30% in old (∼27 months) compared with young (∼8 months) mice as a result of reduced NO bioavailability (P < 0.05). Acute (ex vivo) and chronic (4 weeks in drinking water) administration of MitoQ completely restored EDD in older mice by improving NO bioavailability. There were no effects of age or MitoQ on endothelium‐independent dilation to sodium nitroprusside. The improvements in endothelial function with MitoQ supplementation were associated with the normalization of age‐related increases in total and mitochondria‐derived arterial superoxide production and oxidative stress (nitrotyrosine abundance), as well as with increases in markers of vascular mitochondrial health, including antioxidant status. MitoQ also reversed the age‐related increase in endothelial susceptibility to acute mitochondrial damage (rotenone‐induced impairment in EDD). Our results suggest that mitochondria‐derived oxidative stress is an important mechanism underlying the development of endothelial dysfunction in primary ageing. Mitochondria‐targeted antioxidants such as MitoQ represent a promising novel strategy for the preservation of vascular endothelial function with advancing age and the prevention of age‐related CVD.
Evidence on the association between mental health disorders and cancer risk is inconclusive, despite well-established associations between mental health disorders and lifestyle factors such as ...smoking. This study examines the relationships between depression, anxiety and cancer risk, and the potential mediating effects of lifestyle factors.
A study of 34,571 participants aged 40-69 years in the CARTaGENE cohort was conducted. Depression was defined by questionnaire (PHQ-9), antidepressant use, and a composite of questionnaire, antidepressant use, or lifetime self-reported physician diagnosis. Anxiety was defined by questionnaire (GAD-7). Co-morbid depression and anxiety was also assessed. Cox regression models were used to investigate associations between mental health and risk of prostate, lung, and all cancers combined. Mediating effects of lifestyle factors were assessed using Baron and Kenny mediation criteria.
There were positive associations between mental health disorders, all cancers and lung cancer risk, however with the exception of anxiety and lung cancer in women (Hazard Ratio HR = 1.67, 95% CI: 1.01-2.76), associations were attenuated with adjustment for sociodemographics, health status and lifestyle factors. In the mediation analysis, smoking accounted for 27%, 18%, and 26%, of the total effect between depression (PHQ-9), anxiety, and co-morbidity and lung cancer, respectively in women. In men, smoking accounted for 17% of the total effect between depression (PHQ-9, antidepressant, or lifetime self-report of physician diagnosis) and all cancers.
Positive associations were observed between mental health disorders, all cancer and lung cancer risk, however most relationships were attenuated with adjustment for lifestyle factors. Smoking status mediated a significant proportion of the relationships between mental health disorders and cancer risk.
Objective Predominantly plant-based diets can co-benefit human physical health and the planet. Young adults appear to be on the forefront of the shift to plant-based diets. However, little is known ...about the relationship between plant-based diets and mental health in this population even though mental health disorders contribute substantially to the global burden of disease, particularly among this age group. Design In this cross-sectional study we utilize a biopsychosocial framework to assess the association between dietary intake and mental health and wellbeing. Mental health was assessed using self-reported measures of anxiety (GAD-7), depression (PHQ-9) and quality of life (single-item). Dietary intake in the prior month was assessed using a dietary screener (DSQ) and participants were asked to self-identify a diet preference (e.g., vegan). Setting and participants 339 university undergraduate students. Results A principal component analysis of dietary intake found three dominant dietary patterns (plant-based, animal-based, and 'junk foods'); 28.1% (n = 95) of participants self-identified as pescatarian, vegetarian, vegan, other. The association between dietary patterns, diet preference and mental health was assessed through regression analysis. After controlling for covariables, we found a significant positive association between the junk food component and depression (z-score beta = .21, pless than or equal to.001; adj. R.sup.2 = .39) and anxiety (z-score beta = .14; pless than or equal to.001; adj. R.sup.2 = .32) while no association was found between plant-based, animal-based or self-identified diet preference and the mental health measures. Conclusions We did not find a negative association between predominantly plant-based diet patterns and mental health and wellbeing. It is important to consider dietary composition and to conceptualize diet as a health behaviour that is embedded in a biopsychosocial framework.
An estimated 33%-40% of patients in Canada report financial distress following a cancer diagnosis, including worrying about mortgage payments, depleting their savings, and returning to work before ...being physically ready. Financial toxicity, which refers to the direct, indirect and emotional costs to patients following a cancer diagnosis, is increasingly recognized as a risk factor for poor health and cancer outcomes. Here, Wood and Murphy discuss how financial toxicity can manifest for patients with cancer in Canada and how to address it. Although Canada's health care systems offer free primary and hospital care to residents, people with cancer often face substantial costs that must be paid out of pocket, including those for cancer drugs and treatments, at-home medical equipment, home care, and nutritional supplements. Unlike drugs and services provided in hospital, at-home health services and take-home prescription drugs are not required to be publicly funded under the Canada Health Act. The proposal for the Canada Pharmacare Act frequently references the cost of cancer drugs as an example of the burden of drug costs for people in Canada and the need for more comprehensive, national drug funding.
Excess reactive oxygen species production by mitochondria is a key mechanism of age-related vascular dysfunction. Our laboratory has shown that supplementation with the mitochondrial-targeted ...antioxidant MitoQ improves vascular endothelial function by reducing mitochondrial reactive oxygen species and ameliorates arterial stiffening in old mice, but the effects in humans are unknown. Here, we sought to translate our preclinical findings to humans and determine the safety and efficacy of MitoQ. Twenty healthy older adults (60-79 years) with impaired endothelial function (brachial artery flow-mediated dilation <6%) underwent 6 weeks of oral supplementation with MitoQ (20 mg/d) or placebo in a randomized, placebo-controlled, double-blind, crossover design study. MitoQ was well tolerated, and plasma MitoQ was higher after the treatment versus placebo period (
<0.05). Brachial artery flow-mediated dilation was 42% higher after MitoQ versus placebo (
<0.05); the improvement was associated with amelioration of mitochondrial reactive oxygen species-related suppression of endothelial function (assessed as the increase in flow-mediated dilation with acute, supratherapeutic MitoQ 160 mg administration; n=9;
<0.05). Aortic stiffness (carotid-femoral pulse wave velocity) was lower after MitoQ versus placebo (
<0.05) in participants with elevated baseline levels (carotid-femoral pulse wave velocity >7.60 m/s; n=11). Plasma oxidized LDL (low-density lipoprotein), a marker of oxidative stress, also was lower after MitoQ versus placebo (
<0.05). Participant characteristics, endothelium-independent dilation (sublingual nitroglycerin), and circulating markers of inflammation were not different (all
>0.1). These findings in humans extend earlier preclinical observations and suggest that MitoQ and other therapeutic strategies targeting mitochondrial reactive oxygen species may hold promise for treating age-related vascular dysfunction.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT02597023.
Research suggests that colorectal cancer (CRC) is associated with mental health disorders, primarily anxiety and depression. To synthesize this evidence, we conducted a systematic review and ...meta-analysis of studies evaluating the onset of anxiety and depression among patients with CRC. We searched EMBASE and Medline from inception to June 2022. We included original, peer-reviewed studies that: used an epidemiologic design; included patients with CRC and a comparator group of individuals without cancer; and evaluated anxiety and depression as outcomes. We used random effects models to obtain pooled measures of associations. Quality assessment was completed using the Newcastle-Ottawa scale. Of 7326 articles identified, 8 were eligible; of which 6 assessed anxiety and depression and 2 assessed depression only. Meta-analyses showed a non-significant association between CRC and anxiety (pooled HR 1.67; 95% CI 0.88 to 3.17) and a significant association between CRC and depression (pooled HR 1.78; 95% CI 1.23 to 2.57). Predictors of anxiety and depression among patients with CRC included clinical characteristics (e.g., comorbidities, cancer stage, cancer site), cancer treatment (e.g., radiotherapy, chemotherapy, colostomy), and sociodemographic characteristics (e.g., age, sex). The impacts of anxiety and depression in patients with CRC included increased mortality and decreased quality of life. Altogether, our systematic review and meta-analysis quantified the risks and impacts of CRC on anxiety and depression, particularly an increased risk of depression after CRC diagnosis. Findings provide support for oncologic care that encompasses mental health supports for patients with CRC.
Certain population sub-groups in the United States are vulnerable to micronutrient malnutrition. Nationally representative data from the National Health and Nutrition Examination Survey (NHANES) ...describing the biochemical status of vitamins A, B6, B12, C, D, E, folate, and anemia, were aggregated to determine the overall risk of multiple concurrent deficiencies in U.S. children and adults (
= 15,030) aged >9 years. The prevalence of deficiency risk according to socio-demographic, life-stage, dietary supplement use, and dietary adequacy categories was investigated. Thirty-one percent of the U.S. population was at risk of at least one vitamin deficiency or anemia, with 23%, 6.3%, and 1.7% of the U.S. population at risk of deficiency in 1, 2, or 3-5 vitamins or anemia, respectively. A significantly higher deficiency risk was seen in women (37%), non-Hispanic blacks (55%), individuals from low income households (40%), or without a high school diploma (42%), and underweight (42%) or obese individuals (39%). A deficiency risk was most common in women 19-50 years (41%), and pregnant or breastfeeding women (47%). Dietary supplement non-users had the highest risk of any deficiency (40%), compared to users of full-spectrum multivitamin-multimineral supplements (14%) and other dietary supplement users (28%). Individuals consuming an adequate diet based on the Estimated Average Requirement had a lower risk of any deficiency (16%) than those with an inadequate diet (57%). Nearly one-third of the U.S. population is at risk of deficiency in at least one vitamin, or has anemia.
Cardiovascular diseases (CVD) are the leading cause of death worldwide and aging is the primary risk factor for CVD. The development of vascular dysfunction, including endothelial dysfunction and ...stiffening of the large elastic arteries (i.e., the aorta and carotid arteries), contribute importantly to the age-related increase in CVD risk. Vascular aging is driven in large part by oxidative stress, which reduces bioavailability of nitric oxide and promotes alterations in the extracellular matrix. A key upstream driver of vascular oxidative stress is age-associated mitochondrial dysfunction. This review will focus on vascular mitochondria, mitochondrial dysregulation and mitochondrial reactive oxygen species (ROS) production and discuss current evidence for prevention and treatment of vascular aging via lifestyle and pharmacological strategies that improve mitochondrial health. We will also identify promising areas and important considerations ('research gaps') for future investigation.
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