Polyphenols as an Effective Therapeutic Intervention Against Cognitive Decline During Normal and Pathological Brain Aging.

SIRT1 in Neurodevelopment and Brain Senescence

Abstract: Sirtuins are nicotinamide adenine dinucleotide (NAD+)-dependent deacylases that have traditionally been linked with calorie restriction and aging in mammals. These proteins also play an important role in maintaining neuronal health during aging. During neuronal development, the SIR2 ortholog SIRT1 is structurally important, promoting axonal elongation, neurite outgrowth, and dendritic branching. This sirtuin also plays a role in memory formation by modulating synaptic plasticity. Hypothalamic functions that affect feeding behavior, endocrine function, and circadian rhythmicity are all regulated by SIRT1. Finally, SIRT1 plays protective roles in several neurodegenerative diseases including Alzheimer's, Parkinson's, and motor neuron diseases, which may relate to its functions in metabolism, stress resistance, and genomic stability. Drugs that activate SIRT1 may offer a promising approach to treat these disorders.

Insight into Polyphenol and Gut Microbiota Crosstalk: Are Their Metabolites the Key to Understand Protective Effects against Metabolic Disorders?

Abstract: Lifestyle factors, especially diet and nutrition, are currently regarded as essential avenues to decrease modern-day cardiometabolic disorders (CMD), including obesity, metabolic syndrome, type 2 diabetes, and atherosclerosis. Many groups around the world attribute these trends, at least partially, to bioactive plant polyphenols given their anti-oxidant and anti-inflammatory actions. In fact, polyphenols can prevent or reverse the progression of disease processes through many distinct mechanisms. In particular, the crosstalk between polyphenols and gut microbiota, recently unveiled thanks to DNA-based tools and next generation sequencing, unravelled the central regulatory role of dietary polyphenols and their intestinal micro-ecology metabolites on the host energy metabolism and related illnesses. The objectives of this review are to: (1) provide an understanding of classification, structure, and bioavailability of dietary polyphenols; (2) underline their metabolism by gut microbiota; (3) highlight their prebiotic effects on microflora; (4) discuss the multifaceted roles of their metabolites in CMD while shedding light on the mechanisms of action; and (5) underscore their ability to initiate host epigenetic regulation. In sum, the review clearly documents whether dietary polyphenols and micro-ecology favorably interact to promote multiple physiological functions on human organism.

Long-COVID syndrome-associated brain fog and chemofog: Luteolin to the rescue.

Abstract: COVID-19 leads to severe respiratory problems, but also to long-COVID syndrome associated primarily with cognitive dysfunction and fatigue. Long-COVID syndrome symptoms, especially brain fog, are similar to those experienced by patients undertaking or following chemotherapy for cancer (chemofog or chemobrain), as well in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) or mast cell activation syndrome (MCAS). The pathogenesis of brain fog in these illnesses is presently unknown but may involve neuroinflammation via mast cells stimulated by pathogenic and stress stimuli to release mediators that activate microglia and lead to inflammation in the hypothalamus. These processes could be mitigated by phytosomal formulation (in olive pomace oil) of the natural flavonoid luteolin.

Common plant flavonoids prevent the assembly of amyloid curli fibres and can interfere with bacterial biofilm formation

Abstract: Like all macroorganisms, plants have to control bacterial biofilm formation on their surfaces. On the other hand, biofilms are highly tolerant against antimicrobial agents and other stresses. Consequently, biofilms are also involved in human chronic infectious diseases, which generates a strong demand for anti-biofilm agents. Therefore, we systematically explored major plant flavonoids as putative anti-biofilm agents using different types of biofilms produced by Gram-negative and Gram-positive bacteria. In Escherichia coli macrocolony biofilms, the flavone luteolin and the flavonols myricetin, morin and quercetin were found to strongly reduce the extracellular matrix. These agents directly inhibit the assembly of amyloid curli fibres by driving CsgA subunits into an off-pathway leading to SDS-insoluble oligomers. In addition, they can interfere with cellulose production by still unknown mechanisms. Submerged biofilm formation, however, is hardly affected. Moreover, the same flavonoids tend to stimulate macrocolony and submerged biofilm formation by Pseudomonas aeruginosa. For Bacillus subtilis, the flavonone naringenin and the chalcone phloretin were found to inhibit growth. Thus, plant flavonoids are not general anti-biofilm compounds but show species-specific effects. However, based on their strong and direct anti-amyloidogenic activities, distinct plant flavonoids may provide an attractive strategy to specifically combat amyloid-based biofilms of some relevant pathogens.

Impact of Polyphenolic-Food on Longevity: An Elixir of Life. An Overview.

Abstract: 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.

Polyphenols: food sources and bioavailability

Abstract: Polyphenols are abundant micronutrients in our diet, and evidence for their role in the prevention of degenerative diseases such as cancer and cardiovascular diseases is emerging. The health effects of polyphenols depend on the amount consumed and on their bioavailability. In this article, the nature and contents of the various polyphenols present in food sources and the influence of agricultural practices and industrial processes are reviewed. Estimates of dietary intakes are given for each class of polyphenols. The bioavailability of polyphenols is also reviewed, with particular focus on intestinal absorption and the influence of chemical structure (eg, glycosylation, esterification, and polymerization), food matrix, and excretion back into the intestinal lumen. Information on the role of microflora in the catabolism of polyphenols and the production of some active metabolites is presented. Mechanisms of intestinal and hepatic conjugation (methylation, glucuronidation, sulfation), plasma transport, and elimination in bile and urine are also described. Pharmacokinetic data for the various polyphenols are compared. Studies on the identification of circulating metabolites, cellular uptake, intracellular metabolism with possible deconjugation, biological properties of the conjugated metabolites, and specific accumulation in some target tissues are discussed. Finally, bioavailability appears to differ greatly between the various polyphenols, and the most abundant polyphenols in our diet are not necessarily those that have the best bioavailability profile. A thorough knowledge of the bioavailability of the hundreds of dietary polyphenols will help us to identify those that are most likely to exert protective health effects.

Astrocyte–endothelial interactions at the blood–brain barrier

Abstract: The blood-brain barrier, which is formed by the endothelial cells that line cerebral microvessels, has an important role in maintaining a precisely regulated microenvironment for reliable neuronal signalling. At present, there is great interest in the association of brain microvessels, astrocytes and neurons to form functional 'neurovascular units', and recent studies have highlighted the importance of brain endothelial cells in this modular organization. Here, we explore specific interactions between the brain endothelium, astrocytes and neurons that may regulate blood-brain barrier function. An understanding of how these interactions are disturbed in pathological conditions could lead to the development of new protective and restorative therapies.

Epidemiology of Parkinson's disease

Abstract: The causes of Parkinson's disease (PD), the second most common neurodegenerative disorder, are still largely unknown. Current thinking is that major gene mutations cause only a small proportion of all cases and that in most cases, non-genetic factors play a part, probably in interaction with susceptibility genes. Numerous epidemiological studies have been done to identify such non-genetic risk factors, but most were small and methodologically limited. Larger, well-designed prospective cohort studies have only recently reached a stage at which they have enough incident patients and person-years of follow-up to investigate possible risk factors and their interactions. In this article, we review what is known about the prevalence, incidence, risk factors, and prognosis of PD from epidemiological studies.

High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease.

Abstract: Here we show that in substantia nigra neurons from both aged controls and individuals with Parkinson disease, there is a high level of deleted mitochondrial DNA (mtDNA) (controls, 43.3% ± 9.3%; individuals with Parkinson disease, 52.3% ± 9.3%). These mtDNA mutations are somatic, with different clonally expanded deletions in individual cells, and high levels of these mutations are associated with respiratory chain deficiency. Our studies suggest that somatic mtDNA deletions are important in the selective neuronal loss observed in brain aging and in Parkinson disease.

Neural plasticity in the ageing brain

Abstract: The mechanisms involved in plasticity in the nervous system are thought to support cognition, and some of these processes are affected during normal ageing. Notably, cognitive functions that rely on the medial temporal lobe and prefrontal cortex, such as learning, memory and executive function, show considerable age-related decline. It is therefore not surprising that several neural mechanisms in these brain areas also seem to be particularly vulnerable during the ageing process. In this review, we discuss major advances in our understanding of age-related changes in the medial temporal lobe and prefrontal cortex and how these changes in functional plasticity contribute to behavioural impairments in the absence of significant pathology.