scholarly journals A Review of Dietary (Phyto)Nutrients for Glutathione Support

Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 2073 ◽  
Author(s):  
Deanna M. Minich ◽  
Benjamin I. Brown

Glutathione is a tripeptide that plays a pivotal role in critical physiological processes resulting in effects relevant to diverse disease pathophysiology such as maintenance of redox balance, reduction of oxidative stress, enhancement of metabolic detoxification, and regulation of immune system function. The diverse roles of glutathione in physiology are relevant to a considerable body of evidence suggesting that glutathione status may be an important biomarker and treatment target in various chronic, age-related diseases. Yet, proper personalized balance in the individual is key as well as a better understanding of antioxidants and redox balance. Optimizing glutathione levels has been proposed as a strategy for health promotion and disease prevention, although clear, causal relationships between glutathione status and disease risk or treatment remain to be clarified. Nonetheless, human clinical research suggests that nutritional interventions, including amino acids, vitamins, minerals, phytochemicals, and foods can have important effects on circulating glutathione which may translate to clinical benefit. Importantly, genetic variation is a modifier of glutathione status and influences response to nutritional factors that impact glutathione levels. This narrative review explores clinical evidence for nutritional strategies that could be used to improve glutathione status.

2021 ◽  
Vol 2021 ◽  
pp. 1-30
Author(s):  
Fengming Xu ◽  
Hans-Michael Tautenhahn ◽  
Olaf Dirsch ◽  
Uta Dahmen

Aging is a natural life process which leads to a gradual decline of essential physiological processes. For the liver, it leads to alterations in histomorphology (steatosis and fibrosis) and function (protein synthesis and energy generation) and affects central hepatocellular processes (autophagy, mitochondrial respiration, and hepatocyte proliferation). These alterations do not only impair the metabolic capacity of the liver but also represent important factors in the pathogenesis of malignant liver disease. Autophagy is a recycling process for eukaryotic cells to degrade dysfunctional intracellular components and to reuse the basic substances. It plays a crucial role in maintaining cell homeostasis and in resisting environmental stress. Emerging evidence shows that modulating autophagy seems to be effective in improving the age-related alterations of the liver. However, autophagy is a double-edged sword for the aged liver. Upregulating autophagy alleviates hepatic steatosis and ROS-induced cellular stress and promotes hepatocyte proliferation but may aggravate hepatic fibrosis. Therefore, a well-balanced autophagy modulation strategy might be suitable to alleviate age-related liver dysfunction. Conclusion. Modulation of autophagy is a promising strategy for “rejuvenation” of the aged liver. Detailed knowledge regarding the most devastating processes in the individual patient is needed to effectively counteract aging of the liver without causing obvious harm.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Megan C. Bakeberg ◽  
Madison E. Hoes ◽  
Anastazja M. Gorecki ◽  
Frances Theunissen ◽  
Abigail L. Pfaff ◽  
...  

AbstractAbnormal mitochondrial function is a key process in the pathogenesis of Parkinson’s disease (PD). The central pore-forming protein TOM40 of the mitochondria is encoded by the translocase of outer mitochondrial membrane 40 homologue gene (TOMM40). The highly variant ‘523’ poly-T repeat is associated with age-related cognitive decline and age of onset in Alzheimer’s disease, but whether it plays a role in modifying the risk or clinical course of PD it yet to be elucidated. The TOMM40 ‘523’ allele length was determined in 634 people with PD and 422 healthy controls from an Australian cohort and the Parkinson’s Progression Markers Initiative (PPMI) cohort, using polymerase chain reaction or whole genome sequencing analysis. Genotype and allele frequencies of TOMM40 ‘523’ and APOE ε did not differ significantly between the cohorts. Analyses revealed TOMM40 ‘523’ allele groups were not associated with disease risk, while considering APOE ε genotype. Regression analyses revealed the TOMM40 S/S genotype was associated with a significantly later age of symptom onset in the PPMI PD cohort, but not after correction for covariates, or in the Australian cohort. Whilst variation in the TOMM40 ‘523’ polymorphism was not associated with PD risk, the possibility that it may be a modifying factor for age of symptom onset warrants further investigation in other PD populations.


Author(s):  
Tatsunori Suzuki ◽  
Takahiro Kishikawa ◽  
Tatsuyuki Sato ◽  
Norihiko Takeda ◽  
Yuki Sugiura ◽  
...  

AbstractMutational activation of the KRAS gene occurs in almost all pancreatic ductal adenocarcinoma (PDAC) and is the earliest molecular event in their carcinogenesis. Evidence has accumulated of the metabolic reprogramming in PDAC, such as amino acid homeostasis and autophagic flux. However, the biological effects of KRAS mutation on metabolic reprogramming at the earlier stages of PDAC carcinogenesis are unclear. Here we report dynamic metabolic reprogramming in immortalized human non-cancerous pancreatic ductal epithelial cells, in which a KRAS mutation was induced by gene-editing, which may mimic early pancreatic carcinogenesis. Similar to the cases of PDAC, KRAS gene mutation increased the dependency on glucose and glutamine for maintaining the intracellular redox balance. In addition, the intracellular levels of amino acids were significantly decreased because of active protein synthesis, and the cells required greater autophagic flux to maintain their viability. The lysosomal inhibitor chloroquine significantly inhibited cell proliferation. Therefore, metabolic reprogramming is an early event in carcinogenesis initiated by KRAS gene mutation, suggesting a rationale for the development of nutritional interventions that suppress or delay the development of PDAC.


Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 507
Author(s):  
Rosaria Meccariello ◽  
Stefania D’Angelo

Aging and, particularly, the onset of age-related diseases are associated with tissue dysfunction and macromolecular damage, some of which can be attributed to accumulation of oxidative damage. Recently, growing interest has emerged on the beneficial effects of plant-based diets for the prevention of chronic diseases including obesity, diabetes, and cardiovascular disease. Several studies collectively suggests that the intake of polyphenols and their major food sources may exert beneficial effects on improving insulin resistance and related diabetes risk factors, such as inflammation and oxidative stress. They are the most abundant antioxidants in the diet, and their intake has been associated with a reduced aging in humans. Polyphenolic intake has been shown to be effective at ameliorating several age-related phenotypes, including oxidative stress, inflammation, impaired proteostasis, and cellular senescence, both in vitro and in vivo. In this paper, effects of these phytochemicals (either pure forms or polyphenolic-food) are reviewed and summarized according to affected cellular signaling pathways. Finally, the effectiveness of the anti-aging preventive action of nutritional interventions based on diets rich in polyphenolic food, such as the diets of the Blue zones, are discussed.


2021 ◽  
pp. 1-9
Author(s):  
Karen Patricia Best ◽  
Judith Gomersall ◽  
Maria Makrides

Worldwide, around 15 million preterm babies are born annually, and despite intensive research, the specific mechanisms triggering preterm birth (PTB) remain unclear. Cost-effective primary prevention strategies to reduce PTB are required, and nutritional interventions offer a promising alternative. Nutrients contribute to a variety of mechanisms that are potentially important to preterm delivery, such as infection, inflammation, oxidative stress, and muscle contractility. Several observational studies have explored the association between dietary nutrients and/or dietary patterns and PTB, often with contrasting results. Randomized trial evidence on the effects of supplementation with zinc, multiple micronutrients (iron and folic acid), and vitamin D is promising; however, results are inconsistent, and many studies are not adequately powered for outcomes of PTB. Large-scale clinical trials with PTB as the primary outcome are needed before any firm conclusions can be drawn for these nutrients. The strongest evidence to date for a nutritional solution exists for omega-3 long-chain polyunsaturated fatty acids (LCPUFAs), key nutrients in fish. In 2018, a Cochrane Review (including 70 studies) showed that prenatal supplementation with omega-3 LCPUFAs reduced the risk of PTB and early PTB (EPTB) compared with no omega-3 supplementation. However, the largest trial of omega-3 supplementation in pregnancy, the Omega-3 to Reduce the Incidence of Prematurity (ORIP) trial (<i>n</i> = 5,544), showed no reduction in EPTB and a reduction in PTB only in a prespecified analysis of singleton pregnancies. Exploratory analyses from the ORIP trial found that women with low baseline total omega-3 status were at higher risk of EPTB, and that this risk was substantially reduced with omega-3 supplementation. In contrast, women with replete or high baseline total omega-3 status were already at low risk of EPTB and additional omega-3 supplementation increased the risk of EPTB compared to control. These findings suggest that determining an individual woman’s PUFA status may be the most precise way to inform recommendations to reduce her risk of PTB.


2021 ◽  
Vol 99 (Supplement_2) ◽  
pp. 25-26
Author(s):  
Sterling H Fahey ◽  
Sarah West ◽  
John M Long ◽  
Carey Satterfield ◽  
Rodolfo C Cardoso

Abstract Gestational nutrient restriction causes epigenetic and phenotypic changes that affect multiple physiological processes in the offspring. Gonadotropes, the cells in the anterior pituitary that secrete luteinizing hormone (LH) and follicle-stimulating hormone (FSH), are particularly sensitive to nutritional changes during fetal development. Our objective herein was to investigate the effects of gestational nutrient restriction on LH protein content and number of gonadotropes in the fetal bovine pituitary. We hypothesized that moderate nutrient restriction during mid to late gestation decreases pituitary LH production, which is associated with a reduced number of gonadotropes. Embryos were produced in vitro with X-bearing semen from a single sire then split to generate monozygotic twins. Each identical twin was transferred to a virgin dam yielding four sets of female twins. At gestational d 158, the dams were randomly assigned into two groups, one fed 100% NRC requirements (control) and the other fed 70% of NRC requirements (restricted) during the last trimester of gestation, ensuring each pair of twins had one twin in each group. At gestational d 265, the fetuses (n = 4/group) were euthanized by barbiturate overdose, and the pituitaries were collected. Western blots were performed using an ovine LH-specific antibody (Dr. A.F. Parlow, NIDDK). The total LH protein content in the pituitary tended to be decreased in the restricted fetuses compared to controls (P &lt; 0.10). However, immunohistochemistry analysis of the pituitary did not reveal any significant changes in the total number of LH-positive cells (control = 460±23 cells/0.5 mm2; restricted = 496±45 cells/0.5 mm2, P = 0.58). In conclusion, while maternal nutrient restriction during gestation resulted in a trend of reduced LH content in the fetal pituitary, immunohistological findings suggest that these changes are likely related to the individual potential of each gonadotrope to produce LH, rather than alterations in cell differentiation during fetal development.


Author(s):  
Lucy Beishon ◽  
Rebecca H. Clough ◽  
Meeriam Kadicheeni ◽  
Tamara Chithiramohan ◽  
Ronney B. Panerai ◽  
...  

AbstractThe population is ageing worldwide, thus increasing the burden of common age-related disorders to the individual, society and economy. Cerebrovascular diseases (stroke, dementia) contribute a significant proportion of this burden and are associated with high morbidity and mortality. Thus, understanding and promoting healthy vascular brain ageing are becoming an increasing priority for healthcare systems. In this review, we consider the effects of normal ageing on two major physiological processes responsible for vascular brain function: Cerebral autoregulation (CA) and neurovascular coupling (NVC). CA is the process by which the brain regulates cerebral blood flow (CBF) and protects against falls and surges in cerebral perfusion pressure, which risk hypoxic brain injury and pressure damage, respectively. In contrast, NVC is the process by which CBF is matched to cerebral metabolic activity, ensuring adequate local oxygenation and nutrient delivery for increased neuronal activity. Healthy ageing is associated with a number of key physiological adaptations in these processes to mitigate age-related functional and structural declines. Through multiple different paradigms assessing CA in healthy younger and older humans, generating conflicting findings, carbon dioxide studies in CA have provided the greatest understanding of intrinsic vascular anatomical factors that may mediate healthy ageing responses. In NVC, studies have found mixed results, with reduced, equivalent and increased activation of vascular responses to cognitive stimulation. In summary, vascular and haemodynamic changes occur in response to ageing and are important in distinguishing “normal” ageing from disease states and may help to develop effective therapeutic strategies to promote healthy brain ageing.


2021 ◽  
Vol 11 (5) ◽  
pp. 2228
Author(s):  
Daniela Galli ◽  
Cecilia Carubbi ◽  
Elena Masselli ◽  
Mauro Vaccarezza ◽  
Valentina Presta ◽  
...  

Reactive Oxygen Species (ROS) are molecules naturally produced by cells. If their levels are too high, the cellular antioxidant machinery intervenes to bring back their quantity to physiological conditions. Since aging often induces malfunctioning in this machinery, ROS are considered an effective cause of age-associated diseases. Exercise stimulates ROS production on one side, and the antioxidant systems on the other side. The effects of exercise on oxidative stress markers have been shown in blood, vascular tissue, brain, cardiac and skeletal muscle, both in young and aged people. However, the intensity and volume of exercise and the individual subject characteristics are important to envisage future strategies to adequately personalize the balance of the oxidant/antioxidant environment. Here, we reviewed the literature that deals with the effects of physical activity on redox balance in young and aged people, with insights into the molecular mechanisms involved. Although many molecular pathways are involved, we are still far from a comprehensive view of the mechanisms that stand behind the effects of physical activity during aging. Although we believe that future precision medicine will be able to transform exercise administration from wellness to targeted prevention, as yet we admit that the topic is still in its infancy.


2019 ◽  
Vol 188 (12) ◽  
pp. 2069-2077
Author(s):  
Priya Duggal ◽  
Christine Ladd-Acosta ◽  
Debashree Ray ◽  
Terri H Beaty

Abstract The field of genetic epidemiology is relatively young and brings together genetics, epidemiology, and biostatistics to identify and implement the best study designs and statistical analyses for identifying genes controlling risk for complex and heterogeneous diseases (i.e., those where genes and environmental risk factors both contribute to etiology). The field has moved quickly over the past 40 years partly because the technology of genotyping and sequencing has forced it to adapt while adhering to the fundamental principles of genetics. In the last two decades, the available tools for genetic epidemiology have expanded from a genetic focus (considering 1 gene at a time) to a genomic focus (considering the entire genome), and now they must further expand to integrate information from other “-omics” (e.g., epigenomics, transcriptomics as measured by RNA expression) at both the individual and the population levels. Additionally, we can now also evaluate gene and environment interactions across populations to better understand exposure and the heterogeneity in disease risk. The future challenges facing genetic epidemiology are considerable both in scale and techniques, but the importance of the field will not diminish because by design it ties scientific goals with public health applications.


1986 ◽  
Vol 80 (7) ◽  
pp. 849-854
Author(s):  
E. Pell ◽  
L. E. Arend ◽  
G. T. Timberlake

Patients with age-related visual loss suffer reduced ability to recognize faces and other scenes in photographs and on television. Recently, progress has been made in image enhancement, using controlled distortion of digitally stored images that increases their usefulness in particular applications. Described are two approaches to image enhancement for the visually impaired. In one approach, the visual losses that characterize individual patients and disease classes are described using detailed measurements of visual degradation transfer functions, which are profiles of loss of image information at various spatial scales. The particular distortion used for image enhancement is then adjusted to the impairment of the individual patient or disease class. A second approach takes advantage of the resemblance between the visual losses of many patients and the degradation of picture information in other applications due to external limitations (e.g., fog and haze) on photography. Several enhancement algorithms have been found useful with such images and may also improve picture recognition by the visually impaired.


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