Is Mitochondrial Dysfunction a Common Root of Noncommunicable Chronic Diseases?
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ABSTRACT:
SUBMITTER: Diaz-Vegas A
PROVIDER: S-EPMC7255501 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundMultimorbidity is the co-occurrence of two or more chronic diseases.ObjectiveThis study, based on self-reported medical diagnosis, aims to investigate the dynamic distribution of multimorbidity across sociodemographic levels and its impacts on health-related issues over 15 years in Brazil using national data.MethodsData were analyzed using descriptive statistics, hypothesis tests, and logistic regression. The study sample comprised 679,572 adults (18-59 years of age) and 115,699 elderly people (≥60 years of age) from the two latest cross-sectional, multiple-cohort, national-based studies: the National Sample Household Survey (PNAD) of 1998, 2003, and 2008, and the Brazilian National Health Survey (PNS) of 2013.ResultsOverall, the risk of multimorbidity in adults was 1.7 times higher in women (odds ratio [OR] 1.73, 95% CI 1.67-1.79) and 1.3 times higher among people without education (OR 1.34, 95% CI 1.28-1.41). Multiple chronic diseases considerably increased with age in Brazil, and people between 50 and 59 years old were about 12 times more likely to have multimorbidity than adults between 18 and 29 years of age (OR 11.89, 95% CI 11.27-12.55). Seniors with multimorbidity had more than twice the likelihood of receiving health assistance in community services or clinics (OR 2.16, 95% CI 2.02-2.31) and of being hospitalized (OR 2.37, 95% CI 2.21-2.56). The subjective well-being of adults with multimorbidity was often worse than people without multiple chronic diseases (OR=12.85, 95% CI: 12.07-13.68). These patterns were similar across all 4 cohorts analyzed and were relatively stable over 15 years.ConclusionsOur study shows little variation in the prevalence of the multimorbidity of chronic diseases in Brazil over time, but there are differences in the prevalence of multimorbidity across different social groups. It is hoped that the analysis of multimorbidity from the two latest Brazil national surveys will support policy making on epidemic prevention and management.
| S-EPMC8663437 | biostudies-literature
Project description:Sporadic inclusion body myositis (sIBM) is an inflammatory myopathy associated, among others, with mitochondrial dysfunction. Similar molecular features are found in Alzheimer's disease (AD) and Type 2 Diabetes Mellitus (T2DM), underlying potential comorbidity. This study aims to evaluate common clinical and molecular hallmarks among sIBM, AD, and T2DM. Comorbidity with AD was assessed in n = 14 sIBM patients by performing neuropsychological and cognitive tests, cranial magnetic resonance imaging, AD cerebrospinal fluid biomarkers (levels of amyloid beta, total tau, and phosphorylated tau at threonine-181), and genetic apolipoprotein E genotyping. In the same sIBM cohort, comorbidity with T2DM was assessed by collecting anthropometric measures and performing an oral glucose tolerance test and insulin determinations. Results were compared to the standard population and other myositis (n = 7 dermatomyositis and n = 7 polymyositis). Mitochondrial contribution into disease was tested by measurement of oxidative/anaerobic and oxidant/antioxidant balances, respiration fluxes, and enzymatic activities in sIBM fibroblasts subjected to different glucose levels. Comorbidity of sIBM with AD was not detected. Clinically, sIBM patients showed signs of misbalanced glucose homeostasis, similar to other myositis. Such misbalance was further confirmed at the molecular level by the metabolic inability of sIBM fibroblasts to adapt to different glucose conditions. Under the standard condition, sIBM fibroblasts showed decreased respiration (0.71 ± 0.08 vs. 1.06 ± 0.04 nmols O2/min; p = 0.024) and increased anaerobic metabolism (5.76 ± 0.52 vs. 3.79 ± 0.35 mM lactate; p = 0.052). Moreover, when glucose conditions were changed, sIBM fibroblasts presented decreased fold change in mitochondrial enzymatic activities (-12.13 ± 21.86 vs. 199.22 ± 62.52 cytochrome c oxidase/citrate synthase ratio; p = 0.017) and increased oxidative stress per mitochondrial activity (203.76 ± 82.77 vs. -69.55 ± 21.00; p = 0.047), underlying scarce metabolic plasticity. These findings do not demonstrate higher prevalence of AD in sIBM patients, but evidences of prediabetogenic conditions were found. Glucose deregulation in myositis suggests the contribution of lifestyle conditions, such as restricted mobility. Additionally, molecular evidences from sIBM fibroblasts confirm that mitochondrial dysfunction may play a role. Monitoring T2DM development and mitochondrial contribution to disease in myositis patients could set a path for novel therapeutic options.
| S-EPMC7290779 | biostudies-literature
Project description:Mitochondria are the repository for various metabolites involved in diverse energy-generating processes, like the TCA cycle, oxidative phosphorylation, and metabolism of amino acids, fatty acids, and nucleotides, which rely significantly on flavoenzymes, such as oxidases, reductases, and dehydrogenases. Flavoenzymes are functionally dependent on biologically active flavin adenine dinucleotide (FAD) or flavin mononucleotide (FMN), which are derived from the dietary component riboflavin, a water soluble vitamin. Riboflavin regulates the structure and function of flavoenzymes through its cofactors FMN and FAD and, thus, protects the cells from oxidative stress and apoptosis. Hence, it is not surprising that any disturbance in riboflavin metabolism and absorption of this vitamin may have consequences on cellular FAD and FMN levels, resulting in mitochondrial dysfunction by reduced energy levels, leading to riboflavin associated disorders, like cataracts, neurodegenerative and cardiovascular diseases, etc. Furthermore, mutations in either nuclear or mitochondrial DNA encoding for flavoenzymes and flavin transporters significantly contribute to the development of various neurological disorders. Moreover, recent studies have evidenced that riboflavin supplementation remarkably improved the clinical symptoms, as well as the biochemical abnormalities, in patients with neuronopathies, like Brown-Vialetto-Van-Laere syndrome (BVVLS) and Fazio-Londe disease. This review presents an updated outlook on the cellular and molecular mechanisms of neurodegenerative disorders in which riboflavin deficiency leads to dysfunction in mitochondrial energy metabolism, and also highlights the significance of riboflavin supplementation in aforementioned disease conditions. Thus, the outcome of this critical assessment may exemplify a new avenue to enhance the understanding of possible mechanisms in the progression of neurodegenerative diseases and may provide new rational approaches of disease surveillance and treatment.
| S-EPMC5447943 | biostudies-literature
Project description:Podocytes are visceral epithelial cells covering the outer surface of glomerular capillaries in the kidney. Blood is filtered through the slit diaphragm of podocytes to form urine. The functional and structural integrity of podocytes is essential for the normal function of the kidney. As a membrane-bound organelle, lysosomes are responsible for the degradation of molecules via hydrolytic enzymes. In addition to its degradative properties, recent studies have revealed that lysosomes may serve as a platform mediating cellular signaling in different types of cells. In the last decade, increasing evidence has revealed that the normal function of the lysosome is important for the maintenance of podocyte homeostasis. Podocytes have no ability to proliferate under most pathological conditions; therefore, lysosome-dependent autophagic flux is critical for podocyte survival. In addition, new insights into the pathogenic role of lysosome and associated signaling in podocyte injury and chronic kidney disease have recently emerged. Targeting lysosomal functions or signaling pathways are considered potential therapeutic strategies for some chronic glomerular diseases. This review briefly summarizes current evidence demonstrating the regulation of lysosomal function and signaling mechanisms as well as the canonical and noncanonical roles of podocyte lysosome dysfunction in the development of chronic glomerular diseases and associated therapeutic strategies.
| S-EPMC7084483 | biostudies-literature
Project description:Neurodegenerative diseases are debilitating and currently incurable conditions causing severe cognitive and motor impairments, defined by the progressive deterioration of neuronal structure and function, eventually causing neuronal loss. Understand the molecular and cellular mechanisms underlying these disorders are essential to develop therapeutic approaches. MicroRNAs (miRNAs) are short non-coding RNAs implicated in gene expression regulation at the post-transcriptional level. Moreover, miRNAs are crucial for different processes, including cell growth, signal transmission, apoptosis, cancer and aging-related neurodegenerative diseases. Altered miRNAs levels have been associated with the formation of reactive oxygen species (ROS) and mitochondrial dysfunction. Mitochondrial dysfunction and ROS formation occur in many neurodegenerative diseases such as Alzheimer's, Parkinson's and Huntington's diseases. The crosstalk existing among oxidative stress, mitochondrial dysfunction and miRNAs dysregulation plays a pivotal role in the onset and progression of neurodegenerative diseases. Based on this evidence, in this review, with a focus on miRNAs and their role in mitochondrial dysfunction in aging-related neurodegenerative diseases, with a focus on their potential as diagnostic biomarkers and therapeutic targets.
| S-EPMC7504116 | biostudies-literature
Project description:Mitochondria are essential organelles for neuronal function and cell survival. Besides the well-known bioenergetics, additional mitochondrial roles in calcium signaling, lipid biogenesis, regulation of reactive oxygen species, and apoptosis are pivotal in diverse cellular processes. The mitochondrial proteome encompasses about 1,500 proteins encoded by both the nuclear DNA and the maternally inherited mitochondrial DNA. Mutations in the nuclear or mitochondrial genome, or combinations of both, can result in mitochondrial protein deficiencies and mitochondrial malfunction. Therefore, mitochondrial quality control by proteins involved in various surveillance mechanisms is critical for neuronal integrity and viability. Abnormal proteins involved in mitochondrial bioenergetics, dynamics, mitophagy, import machinery, ion channels, and mitochondrial DNA maintenance have been linked to the pathogenesis of a number of neurological diseases. The goal of this review is to give an overview of these pathways and to summarize the interconnections between mitochondrial protein dysfunction and neurological diseases.
| S-EPMC9489860 | biostudies-literature
Project description:BackgroundChronic noncommunicable diseases (NCDs) have emerged as a huge global health problem in low- and middle-income countries. The magnitude of the rise of NCDs is particularly visible in Southeast Asia where limited resources have been used to address this rising epidemic, as in the case of Indonesia. Robust evidence to measure growing NCD-related burdens at national and local levels and to aid national discussion on social determinants of health and intra-country inequalities is needed. The aim of this review is (i) to illustrate the burden of risk factors, morbidity, disability, and mortality related to NCDs; (ii) to identify existing policy and community interventions, including disease prevention and management strategies; and (iii) to investigate how and why an inequitable distribution of this burden can be explained in terms of the social determinants of health.MethodsOur review followed the PRISMA guidelines for identifying, screening, and checking the eligibility and quality of relevant literature. We systematically searched electronic databases and gray literature for English- and Indonesian-language studies published between Jan 1, 2000 and October 1, 2015. We synthesized included studies in the form of a narrative synthesis and where possible meta-analyzed their data.ResultsOn the basis of deductive qualitative content analysis, 130 included citations were grouped into seven topic areas: risk factors; morbidity; disability; mortality; disease management; interventions and prevention; and social determinants of health. A quantitative synthesis meta-analyzed a subset of studies related to the risk factors smoking, obesity, and hypertension.ConclusionsOur findings echo the urgent need to expand routine risk factor surveillance and outcome monitoring and to integrate these into one national health information system. There is a stringent necessity to reorient and enhance health system responses to offer effective, realistic, and affordable ways to prevent and control NCDs through cost-effective interventions and a more structured approach to the delivery of high-quality primary care and equitable prevention and treatment strategies. Research on social determinants of health and policy-relevant research need to be expanded and strengthened to the extent that a reduction of the total NCD burden and inequalities therein should be treated as related and mutually reinforcing priorities.
| S-EPMC5478110 | biostudies-literature
Project description:In the absence of cure, the main objectives in the management of patients with mitochondrial disease are symptom control and prevention of complications. While pain is a complicating symptom in many chronic diseases and is known to have a clear impact on quality of life, its prevalence and severity in people with mitochondrial disease is unknown. We conducted a survey of pain symptoms in patients with genetically confirmed mitochondrial disease from two UK mitochondrial disease specialist centres. The majority (66.7%) of patients had chronic pain which was primarily of neuropathic nature. Presence of pain did not significantly impact overall quality of life. The m.3243A>G MTTL1 mutation was associated with higher pain severity and increased the likelihood of neuropathic pain compared to other causative nuclear and mitochondrial gene mutations. Although previously not considered a core symptom in people with mitochondrial disease, pain is a common clinical manifestation, frequently of neuropathic nature, and influenced by genotype. Therefore, pain-related symptoms should be carefully characterised and actively managed in this patient population.
| S-EPMC7306151 | biostudies-literature
Project description:Cardiovascular diseases (CVDs) are serious public health issues and are responsible for nearly one-third of global deaths. Mitochondrial dysfunction is accountable for the development of most CVDs. Mitochondria produce adenosine triphosphate through oxidative phosphorylation and inevitably generate reactive oxygen species (ROS). Excessive ROS causes mitochondrial dysfunction and cell death. Mitochondria can protect against these damages via the regulation of mitochondrial homeostasis. In recent years, mitochondria-targeted therapy for CVDs has attracted increasing attention. Various studies have confirmed that clinical drugs (β-blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor-II blockers) against CVDs have mitochondrial protective functions. An increasing number of cardiac mitochondrial targets have shown their cardioprotective effects in experimental and clinical studies. Here, we briefly introduce the mechanisms of mitochondrial dysfunction and summarize the progression of mitochondrial targets against CVDs, which may provide ideas for experimental studies and clinical trials.
| S-EPMC9140220 | biostudies-literature
Project description:Cardiovascular disease (CVD) is the number one threat that seriously endangers human health. However, the mechanism of their occurrence is not completely clear. Increasing studies showed that mitochondrial dysfunction is closely related to CVD. Possible causes of mitochondrial dysfunction include oxidative stress, Ca2+ disorder, mitochondrial DNA mutations, and reduction of mitochondrial biosynthesis, all of which are closely related to the development of CVD. At present, traditional Chinese medicine (TCM) is widely used in the treatment of CVD. TCM has the therapeutic characteristics of multitargets and multipathways. Studies have shown that TCM can treat CVD by protecting mitochondrial function. Via systematic literature review, the results show that the specific mechanisms include antioxidant stress, regulation of calcium homeostasis, antiapoptosis, and regulation of mitochondrial biosynthesis. This article describes the relationship between mitochondrial dysfunction and CVD, summarizes the TCM commonly used for the treatment of CVD in recent years, and focuses on the regulatory effect of TCM on mitochondrial function.
| S-EPMC7568168 | biostudies-literature