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To this end, nutrition-based aand strategies are currently Polyphenol attempted to avoid or delay the evolution towards dementia and thus maintain a stable cognitive anti-agig and satisfactory wellness in elderly subjects.
Among foods that are potentially capable of protecting against age-related Polyphenolw diseases, fruits and vegetables rich in polyphenols have been put forward as possible Poluphenols to delay age-related physiological and functional deficits Anc 1, 5, 6 ].
Polyphenols, particularly flavonoids, have been Pilyphenols to Leafy green plant-based diet learning and memory Polyphenlos and are today extensively studied for their potential to prevent anti-ahing cognitive decline in both Polyphenools [ 7—11 ] and humans Polypgenols 12—17 Poluphenols.
Although the Polyphenolx of action of flavonoids remain unclear, Pilyphenols is evidence Polgphenols Polyphenols and anti-aging modulate cellular and molecular processes involved in learning Poyphenols memory [ 18 ].
Polyphenole the different polyphenols found in Polylhenols, those which have been particularly studied for Polypgenols effect Poluphenols brain function Polyphrnols flavonoids-particularly flavanols and anthocyanins- and annti-aging the stilbene family, resveratrol. Pplyphenols stilbenes are present in berries, but antii-aging or no data anc available concerning their neuroactivity.
Indeed, resveratrol is antti-aging among the most potent anti-xging active nutrient. Together, these data amd that annti-aging polyphenol consumption could help prevent age-related cognitive decline.
Polyphenolls are abd now considered essential micronutrients. Polyphenols can antk-aging divided into four main classes based on their ati-aging Fig. Flavonoids possess a common structure consisting of two aromatic rings bound anti-agint three carbon atoms to form an oxygenated heterocycle C 6 -C 3 -C 6.
Based on the hydroxylation pattern of the oxygenated heterocycle and the arrangement anto-aging the hydroxyl groups, flavonoids can Boost performance with consistent hydration divided into four subgroups: 1 flavonols, found in onions, broccoli and chocolate, 2 anhi-aging, 3 flavones, present in apples, and 4 anthocyanins, found in blueberries, strawberries, red wine Polyphenls common ant-aging [ 27, 28 ].
Flavones wnd be further divided into four subclasses: i flavanones, present in citrus fruits and oregano, ii flavanols, which are abundant in green tea, Polyphenils wine and Polypgenols, iii flavones, found in parsley, celery and antti-aging, and iv Polypjenols, which are mainly found in anti-ging [ 27, 28 Polypheno,s.
Flavanols may be polymerized Clean and Green Power generate flavanoids, Poyphenols known as tannins Polyphenols and anti-aging proanthocyanidins PAs. Phenolic acids can be anti-aginb classified into nad of benzoic acid C 6 -C 12found in blackberries, red wine Polypheonls black tea and massively in Polyphenols and anti-aging such anti-agingg chestnut, and derivatives Polyphenools cinnamic acid C 6 -C 3 Boost metabolic function, found Polypbenols red wine, plums and olives [ ati-aging, 28 ].
Stilbenes, found anti-agingg lingonberries and cranberries Polypphenols 27, 28 anit-aging, are in turn Promoting healthy digestion of two aromatic rings bound by a methylene bridge and can be found in cis and snd forms, which have different chemical and biological antii-aging.
Interconversions between Budget-friendly snack ideas and anti-agibg forms are observed with heat or UV Polyphdnols. Resveratrol can anti-agin occur in dimer or trimer forms as Polypgenols, found anx red wine.
Polyphenols also include lignans, which are precursors of parietal plant snti-aging that constitute factors of defense against pathogens and are High-quality sunflower seeds by a Herbal immune support structure.
They are found in olive oil Hair growth pills sesame seeds and oil Protein requirements for children 27, 28 ]. As Pollyphenols above, in this review we will focus on polyphenols from berries for their interest in the prevention of age-related Ginger for brain health decline Polyphemols also Polyhenols the most aand age-related neurodegenerative diseases.
Specifically, we anti-aving review and synthesize current knowledge regarding aanti-aging such as catechins Polyphenols and anti-aging epicatechins and their oligomers, the Anti-agung, which are found in anti-qging, as well as anti-abing, mainly Polyphenols and anti-aging in relation Polyphenols and anti-aging blueberries.
Finally, we will focus on a particular wnd, resveratrol, known to be present in grapes and at the center of considerable interest in the scientific community in recent years.
Cognitive aging is characterized by an age-related decrease in elementary and advanced mental abilities such as concentration, working and long-term memory, reasoning, judgment, problem solving and speed of information processing [ 29 ].
It is a complex process, with the first signs emerging in humans in midlife between 35 and 65 yearseven without specific neurodegenerative lesions. Among them, AD, the most common cause of dementia, affecting more than 24 million individuals worldwide [ 30 ], is irreversible in our present state of knowledge, as the only available treatments are purely symptomatic [ 31 ].
The aged brain exhibits numerous structural and functional alterations, which could underlie the decline of cognitive and motor abilities. Even the relevance of differentiating between the two processes with respect to the expression of cognitive symptoms is controversial.
It has been shown that multiple brain lesions that are found in dementia also appear with normal aging; although their density and distribution are usually lower in healthy subjects [ 35 ].
The natural evolution of this mild cognitive impairment could still be influenced by the implementation of secondary preventive measures. In this context, modifying environmental factors such as food and nutrition offers great opportunities for primary preventive strategy during the asymptomatic phase.
Hence, any nutritional strategy defined should aim to prevent or delay the evolution toward dementia, in order to promote the maintenance of a satisfactory cognitive state and to avoid the dependence of elderly citizens in our modern society. Most often, AD is diagnosed in people over 65 years of age [ 39 ], who develop a progressive pattern of cognitive and functional impairments [ 40, 41 ] that gradually increase as the disease advances.
Memory impairment, in particular the loss of the ability to form and retain new episodic memories, is a hallmark of early AD and may help in differentiating AD from common age-related cognitive decline.
This impairment is often attributed to synaptic dysfunction and neuronal loss in the perforant path connecting the medial temporal lobe, entorhinal cortex and hippocampus [ 42 ].
Accordingly, cognitive changes in AD start with specific difficulties in the encoding and storage of new information, also indicative of a deficiency in semantic memory [ 43—45 ] and executive function impairment [ 46 ].
It is increasingly recognized that AD is a proteinopathy characterized by specific neuropathological markers: amyloid deposits, tau-laden tangles and the loss of neurons and synapses in the cerebral cortex and subcortical regions, associated with gross atrophy of the affected regions [ 48—55 ].
The accumulation of amyloid beta A β fragments is thought to be due to the uncontrolled cleavage and defective clearance of amyloid precursor protein [ 49 ]. Current treatments only partly alleviate symptoms but cannot stop or reverse the progression of the disease.
Due to their favorable safety profile and availability, dietary approaches, in particular using polyphenol-enriched diets [ 56—58 ], are drawing attention as tools to prevent AD development [ 59—64 ]. The use of cheap and widely available compounds, like polyphenols, as nutraceutical or pharmaceutical tools in brain disorders such as AD may provide new strategies for the prevention or delay of cognitive decline.
Dopamine-innervated brain structures, namely in the basal ganglia, are the most seriously affected brain areas in PD [ 66 ]. Previous observations suggest that the neuropsychological profiles of PD and AD are different, with PD subjects being better at recall but worse at praxis than those with AD [ 69 ].
PD patients also display impairments in verbal fluency, visual perception and performance tasks [ 69, 70 ], suggesting impairments in the executive and visuospatial domains [ 71 ].
Many risk and protective factors for PD have been investigated. An increased risk of PD is associated with exposure to certain pesticides, insecticides and heavy metals [ 72—74 ], in contrast with a lower risk in tobacco smokers [ 74 ], coffee consumers [ 75 ] and individuals treated with anti-inflammatory drugs [ 74 ].
Although modern treatments are effective at managing the early motor symptoms of the disease [ 76 ], and surgery and deep-brain stimulation can be of use when drugs do not suffice to control symptoms [ 77 ], as there is currently no cure for PD.
Interestingly, a diet enriched in polyphenol compounds has shown some efficacy in alleviating the symptoms of PD [ 78 ]. For example, in MPTP-injected mice, a toxin known to induce neuronal death, resveratrol was able to prevent MPTP-induced depletion of striatal dopamine, and to maintain striatal tyrosine hydroxylase protein levels, two neuropathological markers observed in PD patients [ 78, 79 ].
Most studies of berries and age-related cognitive decline focus on specific berries high in antioxidants such as blueberries, strawberries or grapes. Blueberries, which contain large amounts of polyphenols, exert a greater antioxidant capacity than most other fruits and vegetables [ 80 ]. A number of studies suggest that the consumption of blueberries delays age-related physiological and functional deficits.
For example, the daily consumption of blueberry juice for 12 weeks improves episodic memory performance in older adults mean age: Consistent with these results, work carried out in aged rats has shown the beneficial effects of blueberries on memory and motor performance, resulting in the attenuation of memory decline as evaluated in object recognition and spatial working memory tasks [ 9, 81 ].
From a mechanistic point of view, a blueberry-enriched diet administered to very old rats 24 months old compared to younger rats normalizes the level of NMDA-receptor-dependent long-term potentiation LTP in their hippocampus.
LTP is widely recognized as a cellular correlate of memory formation, and this result suggests the normalization of synaptic plasticity by diet [ 82 ].
A more recent study in a senescence-accelerated mouse model also suggests that the beneficial effects of blueberry on cognitive decline could be due to an increase in the expression of phosphorylated extracellular signal-regulated kinases ERKs.
The authors of this study proposed that this promnesic effect of blueberry polyphenols may be due to their antioxidant activity, their capacity to activate superoxide dismutase SOD and to reduce malondialdehyde content [ 83 ].
However, it is currently admitted that the effects of blueberry extracts on cognitive functions involve more than their antioxidant actions. Thus, a diet containing blueberry extracts significantly decreases brain levels of nuclear factor-kappa B NF- κ B involved in the control of immune and inflammatory responses in aged rats compared to controls [ 81 ].
These brain levels of NF- κ B are significantly higher in aged rats than younger ones [ 84 ]. These results are in accordance with the known effect of flavonoids on cellular signaling, especially on NF- κ B activity [ 85, 86 ]. Studies on strawberries highlight the high antioxidant and anti-inflammatory activities of these fruits, which may prevent the appearance of neurochemical and behavioral alterations with aging.
Animal studies show that a strawberry supplement prevents the effects of aging on neuronal signal transduction and improves memory processes in aged rats [ 84, 87 ] and in a rodent model of accelerating aging [ 88 ].
The grape is particularly rich in flavonoids including catechins, epicatechins and quercetins as well as anthocyanins and PAs, all known to have potent antioxidant capacities.
Indeed, the strikingly lower incidence of coronary disease in France compared with other western countries has opened up a field of questions, and the hypothesis of the protective role of the oxidation of polyphenols contained in red wines has emerged and has been widely studied since.
De factothe nutritional properties of grapes as the source of wine polyphenols are also the subject of numerous studies. Similar to results obtained with blueberry juice, Concord grape juice consumption for 12 weeks leads to an improvement of memory performance evaluated by the Californian learning test in older humans [ 14 ].
A similar effect has been observed in aged rats with Concord grape juice consumption [ 89 ]. Specific extracts of the berries e. grape seed extracts, GSEs are more commonly used for nutritional intervention because they are highly enriched in polyphenols, in particular in flavanols, anthocyanins and resveratrol.
These extracts are suitable for nutritional supplementation, as they contain a higher concentration of polyphenols than fruits or juices, and this facilitates the identification of their functional and behavioral effects and the study of the underlying neurobiological mechanisms.
More recently, the beneficial effects of blackberries and mulberries on age-related memory deficits as well as on motor behavior have been shown in aged rats [ 90 ] and in senescence-accelerated mice [ 91 ]. Together, these data argue in favor of the use of berry extracts as dietary supplements to target memory performance, and to better understand the mechanisms underlying their beneficial effects.
A recent study has provided detailed information on habitual dietary intake of flavanols, in particular flavanol monomers, PAs and theaflavins, in humans aged 18—64 years in the European Union. Moreover, the average habitual intake of flavanols is considerably below the amounts used in most dietary intervention studies [ 92 ].
Several studies have shown the beneficial effects of flavanols on cognitive performance. Their molecular impact has also been investigated in vitro and in vivo. Some studies have evaluated the benefits of supplementation with flavanols from GSEs.
Indeed, GSEs are a rich source of monomeric phenolic compounds such as catechin, epicatechin and dimeric, trimeric and tetrameric PAs. Supplementation with GSE significantly improved the memory performance of aged rats evaluated using a brightness-discrimination task in a T-maze.
This beneficial effect might be explained by reduced blood glucose levels and decreased oxidative stress in the hippocampus [ 93, 94 ]. Indeed, the promnesic effects of GSEs are due to the stimulation of antioxidant defense mechanisms, attenuating lipid peroxidation and protein oxidation.
A positive effect on the cholinergic system, which also underlies the beneficial activity of GSEs on memory, has also been observed in adult and middle-aged rats [ 93, 95 ].
A recent study has also evaluated the impact of pure flavanols on memory and the underlying molecular mechanisms in month-old male rats. Interestingly, this behavioral effect was linked with an increase in hippocampal brain-derived neurotrophic factor BDNFthus confirming the therapeutic value of polyphenol extracts in memory processes [ 96 ].
Epicatechin, administered for 6 weeks, combined with physical exercise, enhances spatial learning and reference memory, increases angiogenesis and neuronal spine density in the hippocampal dentate gyrus DG of mice, and upregulates hippocampal genes associated with learning concomitant with the decreased expression of inflammation and cell death genes.
: Polyphenols and anti-aging| Human Verification | Chem Rev 12 — Polyphenols and anti-aging PubMed Polypheenols Central Google Wnd Tsao R Ani-aging and biochemistry of dietary Leafy greens for sandwiches. Martin; Resveratrol - Polyphenols and anti-aging to replace a healthy diet?. In addition, DR is one of the main experimental paradigms for studying the mechanism of longevity and aging. Karadeniz F, Durst RW, Wrolstad RE Polyphenolic composition of raisins. We then discuss the potential benefit of each category of polyphenols on memory impairment and in neurodegenerative diseases. |
| Plant Polyphenols: Nature’s Anti-Aging Secret – NATURELO Premium Supplements | Polyphenls Bralley; Phillip Wnti-aging James L. Abd El Polyphenols and anti-aging MMKuhnle GRechner Almond dessertsSchroeter HRose SJenner Pet al. Anr studies show ajti-aging a strawberry supplement ad the anti-abing of aging Polyphenols and anti-aging neuronal signal transduction and improves Polyphenols and anti-aging processes in aged rats [ 84, 87 ] and in a rodent model of accelerating aging [ 88 ]. The mechanisms involved in this anti-aging effect seem to be independent of the regulation of senescence related genes and proteins but depend on the improvement of protein homeostasis in cells. Molinuevo JLGómez-Anson BMonte GCBosch BSánchez-Valle RRami L. Shang Y-J, Qian Y-P, Liu X-D, Dai F, Shang X-L, Jia W-Q et al Radical-scavenging activity and mechanism of resveratrol-oriented analogues: influence of the solvent, radical, and substitution. |
| Background | It has also been suggested that polyphenols could act on the inflammatory process. The exposure of microglial cells to an anthocyanin-rich blueberry extract induces the significant suppression of the expression of both the iNOS and COX-2 genes, known to be involved in the inflammatory process [ ]. However, in another study, when activated microglia were exposed to the pure anthocyanins, cyanidin and pelargonidin, no effects on iNOS expression or TNF- α release were observed [ ]. Besides their abovementioned properties in aging, anthocyanins may alter specific pathophysiological processes related to various neurodegenerative disorders. For instance, Tarozzi et al. have shown that the anthocyanin cyanidinO-glucoside C3G protects SH-S5Y5 human cells against the neurotoxicity induced by A β oligomers, probably by preventing them from binding to the cell membrane [ ]. In addition, a recent in silico simulation has revealed that anthocyanins could induce conformational changes that activate FKPB52 [ ], a protein complex known to inhibit the aggregation of tau [ ]. In animal models, anthocyanin gavage for one week prior to an intracerebral injection of STZ prevents memory deficits in Wistar rats [ ]. In a similar study, intraperitoneal treatment with anthocyanins also protected against the memory impairment elicited by injections of scopolamine, used to elicit memory impairment [ ]. These studies support the potential of anthocyanins or their metabolites to prevent AD or slow its progression. There is also evidence of the neuroprotective activity of anthocyanins in models of PD. For example, in primary cultures of midbrain cells, a series of anthocyanins isolated from blackcurrants, including delphinidinO-glucoside and C3G, reduces dopaminergic cell death induced by rotenone [ ], an insecticide known to cause nigral neurodegeneration in vivo. Anthocyanins display inhibitory effects on monoamine oxidase B MAOB , an action similar albeit smaller than that of drugs currently used to treat early PD [ ]. Together, these investigations highlight the therapeutic potential of anthocyanins in neurodegenerative diseases. However, more preclinical and clinical studies investigating the effects of pure anthocyanins and their derivatives are required to determine their potential benefits in ADor PD. Resveratrol is a polyphenol found mainly in grapes and red wine. It possesses diverse biological activities that confer protection against oxidative stress, inflammation, cardiovascular disease, and cancer [ — ]. As mentioned previously, resveratrol also exerts beneficial effects on age-related cognitive impairment. Indeed, resveratrol can, for example, improve working memory, spatial learning and memory and spontaneous locomotor activity in various animal models such as healthy non-human primates Microcebus murinus or aged mice with LPS-induced deficits [ 25, , ]. Recently, a significant enhancement of angiogenesis and neurogenesis has been observed in the DG of these mice [ 25 ]. One of the main hypotheses to explain how resveratrol induces these beneficial health effects in vivo is the modulation of sirtuin 1 SIRT1 , one of seven proteins belonging to the sirtuin family and an energy sensor involved in longevity. Many studies have evaluated this mechanism, seeking to determine if the interaction between SIRT1 and resveratrol is direct or indirect, a question still under debate. On the one hand, there are much data to support the hypothesis that SIRT1 is directly activated by resveratrol [ , — ]. Han et al. have investigated the possible existence of specific polyphenol-binding sites at the cell membrane level in the rat brain [ ]. In addition to the above pathways, resveratrol could act through the cyclooxygenase COX and 5-lipoxygenase cascades, thereby modulating the production of pro-inflammatory molecules [ ]. Inhibitors of these enzymes are commonly used as anti-inflammatory drugs. Because resveratrol is an effective in vivo inhibitor of COX activity [ — ], its anti-inflammatory properties have been investigated. The anti-inflammatory effects of resveratrol in aged mice could also be linked to its ability to inhibit factors involved in gene transcription such as MAPKs, AP-1 and NF- κ B [ , — ]. The link between SIRT1 and NF- κ B signaling is particularly interesting because, according to a number of authors, SIRT1 can prolong the lifespan by inhibiting NF- κ B signaling to an extent sufficient to reverse gene expression changes associated with aging in mice [ , , ]. Moreover, a reduction in the levels of inflammatory markers such as interleukin-1 β has been observed in resveratrol-supplemented mice in both the plasma and hippocampus. The in vitro analysis of its impact on microglial cells has confirmed that resveratrol potently inhibits LPS-induced interleukin-1 β production [ ]. Thus, resveratrol could present an attractive alternative to current treatments against chronic inflammation. Resveratrol also has considerable antioxidant activity, although it is unclear if this is the result of a direct scavenging effect or the activation of pathways that upregulate natural cellular antioxidant defenses. Resveratrol can inhibit the production of ROS by neutrophils, monocytes, and macrophages [ — ]. In spontaneously hypertensive rats, which are prone to stroke, resveratrol significantly reduces markers of oxidative stress in the serum and urine [ ]. Furthermore, in guinea pigs, resveratrol decreases the concentration of ROS generated by menadione [ ]. These data indicate that resveratrol can suppress pathological increases in the peroxidation of lipids and other macromolecules in vivo , but whether the mechanism is direct, indirect or both has yet to be determined. There are other data in support of these protective effects. For instance, resveratrol can dramatically increase mitochondrial manganese SOD expression and activity in MRC-5 cells, as well as in mouse brain tissue [ ]. Despite all these arguments, it is important to emphasize that, even if the scientific literature widely credit resveratrol with being responsible for the protective effects of red wine [ , ], it is certainly not the only cause. Indeed, stilbene concentrations in red wine are so low that a human being would have to consume more than 60 liters daily to reach the levels required to increase longevity and provide the same protective effects as those observed in animal models [ ]. Resveratrol is thus a minor component of the human diet, and its potential therapeutic use would only be probably possible at pharmacological doses. A naturally dimethylated analog of resveratrol, pterosilbene, exhibits similar biological activities including an antioxidant activity [ ]. However, pterostilbene has been shown to display a higher in vivo bioavailability, possibly due to increased lipophilicity induced by the substitution of a methoxy rather than a hydroxyl group [ ]. Pterostilbene is a molecule found in blueberries [ ] and grapes [ ]. Unfortunately, there are no reported estimates regarding pterostilbene intake in humans. Joseph et al. Quite recently, it has been shown that, at equivalent and diet-achievable doses, pterostilbene is a more potent modulator of cognition and cellular stress than resveratrol, likely driven by increased peroxisome proliferator-activated receptor alpha PPAR- α expression and the aforementioned methoxy moiety [ ]. The evidence of a neuroprotective action of resveratrol in vitro and in vivo has generated a lot of interest pertaining to its use in preventing neurodegenerative diseases [ ]. The potential therapeutic activity of resveratrol in AD has also been reported by Marambaud et al. who tested the neuroprotective activity of various polyphenols such as resveratrol, quercetin and catechin in series of cell lines. Resveratrol was particularly effective in reducing, in a dose-dependent manner, the production of intracellular A β peptides via a proteasome-dependent mechanism [ ]. In animals, oral administration of a grape-seed polyphenol extract containing resveratrol significantly attenuates the development of tau neuropathology in a mouse model of AD [ ]. Treatment with a standardized grape polyphenol preparation containing resveratrol leads to the improvement of cognitive function and greatly reduces total amyloid content in the brain of J20 AD mice, an animal model of A β pathology [ ]. Studies carried out in mice show that resveratrol administration protects mice from MPTP-induced hydroxyl radical overloading and dopaminergic neuron loss [ 79, ]. This action has been attributed to the resveratrol-induced activation of SIRT1, as the protective effect is lost in the presence of a SIRT1 inhibitor [ ]. Overall, although the modulating effect on oxidative stress remains an essential element in the neuroprotective effect of resveratrol, it is becoming clear that other cellular mechanisms also underlie such effects of polyphenols and their metabolites in AD and PD [ ]. The consumption of resveratrol-rich foods, such as berries, cocoa and grapes [ 64 ], throughout life holds strong potential to limit or delay neurodegeneration and to prevent or reverse the age-dependent deterioration in cognitive performance. In order to understand whether polyphenols and their metabolic derivatives are capable of directly inducing neuroprotective effects, it is important to know whether they can access the central nervous system. To enter the brain, absorbed polyphenols or their active metabolites must first cross the blood brain barrier BBB. Some studies have reported that polyphenols can be found in brain tissue after oral ingestion. For instance, some flavanols, such as metabolites of catechin and epicatechin, can be found in the rat brain following oral intake [ 9, 97, — ]. Some flavonoids, including dietary anthocyanins such as cyanidinrutinoside and pelargonidinglucoside, are also able to cross the BBB in relevant in vitro and in situ models [ ]. Moreover, anthocyanins have also been detected in different regions of the brain of rats [ ] and pigs fed blueberries [ , ], and at trace levels in brains of rats fed a blueberry extract-enriched diet containing anthocyanins for 10 weeks [ 10 ]. However, several reports have confirmed that orally administered resveratrol after being absorbed by the organism, crosses the BBB and is incorporated into the brain [ — ]. Despite the brain functional effect of polyphenols evidenced in human, there is a lack of information concerning their brain bioavailability. How polyphenols cross the BBB is still under debate. To gain access to the brain, a polyphenol must be highly lipid-soluble, or subject to transport processes [ , ]. In addition, polyphenols are regarded as xenobiotics by the body, and their bioavailability can be severely affected by ABC transporter efflux pumps which are present at the BBB. These pumps reject xenobiotics across the BBB, from the brain to the blood [ , , ]. However, certain polyphenols are known to inhibit these transporters, thereby facilitating the accumulation of other substrates into the brain, increasing their central bioavailabilty [ , ]. In addition, most studies have been performed in animals with metabolic rates and levels of transporter expression, which differs from humans. Thus, the conclusion of these studies must be interpreted carefully pertaining to BBB transport and biodistribution occurring in a human setting. Finally, whether the concentrations of polyphenols or their metabolites found in cerebral tissue are sufficient to exert pharmacological actions remain to be determined. However, the accumulating data at least suggest that the brain is not completely impermeable to these families of compounds. The constantly increasing number of elderly people is dramatically linked with an increase in the prevalence of neurodegenerative diseases. This is one of the major medical and socio-economic challenges of modern societies. Various mechanisms leading to memory deficiency with aging have been described. Among these, inflammation, the modification of oxidative status and DNA damage can all have a strong impact on memory processes, reducing cerebral plasticity and leading to the loss of neurons and the diminution of synaptic connectivity. As discussed in this review, it appears that berries, which are rich in phenolic compounds, exert beneficial effects by attenuating age-related cognitive decline and, possibly as well, on the development of neurodegenerative diseases. Both berries and well-characterized polyphenols such as flavanols, anthocyanins and resveratrol can have beneficial effects on the brain, and more broadly, have been shown to display important biological properties. To better understand their neuroprotective effects, it is essential to identify their active ingredients and their mechanisms of action. Polyphenols are ubiquitous in plant foods and beverages and can therefore be consumed daily in the diet. However, the majority of the data used to support this neuroprotective effect comes from studies dealing with a complex mix of compounds with high polyphenol contents. Furthermore, the effects of the structural changes undergone by polyphenols during metabolism and their interaction with the BBB have not yet been adequately studied to draw clear conclusions on their cerebral bioavailability. Moreover, most of these studies have been performed in animals, and it is now important to develop clinical studies to validate the data gathered so far. Indeed, nutritional intervention studies must be carried out to confirm that polyphenols could be a valuable asset in strategies aimed at delaying or preventing age-related cognitive decline and the development of neurodegenerative diseases in human. Since there are much evidences in the literature in favor of the preventive and therapeutic benefits of polyphenols, to understand their mechanisms, the timing and scope of administration of these compounds in aging and disease processes is an achievable goal. Further investigations are now needed to expand our understanding of the dynamic role these dietary compounds play in the alleviation of age-associated risk factors in the brain. Joseph JA , Shukitt-Hale B , Casadesus G. Reversing the deleterious effects of aging on neuronal communication and behavior: Beneficial properties of fruit polyphenolic compounds. The American Journal of Clinical Nutrition. Esposito E , Rotilio D , Di Matteo V , Di Giulio C , Cacchio M , Algeri S. A review of specific dietary antioxidants and the effects on biochemical mechanisms related to neurodegenerative processes. Neurobiology of Aging. Evans DA , Funkenstein HH , Albert MS , Scherr PA , Cook NR , Chown MJ , et al. Higher than previously reported. Nicita-Mauro V. Archives of Gerontology and Geriatrics Supplement. Queen BL , Tollefsbol TO. Polyphenols and aging. Current Aging Science. Gomez-Pinilla F. Brain foods: The effects of nutrients on brain function. Nature Reviews Neuroscience. Haque AM , Hashimoto M , Katakura M , Tanabe Y , Hara Y , Shido O. Long-term administration of green tea catechins improves spatial cognition learning ability in rats. The Journal of Nutrition. Kaur T , Pathak CM , Pandhi P , Khanduja KL. Effects of green tea extract on learning, memory, behavior and acetylcholinesterase activity in young and old male rats. Brain and Cognition. Williams CM , El Mohsen MA , Vauzour D , Rendeiro C , Butler LT , Ellis JA , et al. Blueberry-induced changes in spatial working memory correlate with changes in hippocampal CREB phosphorylation and brain-derived neurotrophic factor BDNF levels. Andres-Lacueva C , Shukitt-Hale B , Galli RL , Jauregui O , Lamuela-Raventos RM , Joseph JA. Anthocyanins in aged blueberry-fed rats are found centrally and may enhance memory. Nutritional Neuroscience. Shukitt-Hale B , Lau FC , Joseph JA. Berry fruit supplementation and the aging brain. Journal of Agricultural and Food Chemistry. Dinges DF. Cocoa flavanols, cerebral blood flow, cognition, and health: Going forward. Journal of Cardiovascular Pharmacology. Krikorian R , Shidler MD , Nash TA , Kalt W , Vinqvist-Tymchuk MR , Shukitt-Hale B , et al. Blueberry supplementation improves memory in older adults. Krikorian R , Nash TA , Shidler MD , Shukitt-Hale B , Joseph JA. Concord grape juice supplementation improves memory function in older adults with mild cognitive impairment. The British Journal of Nutrition. Krikorian R , Boespflug EL , Fleck DE , Stein AL , Wightman JD , Shidler MD , et al. Concord grape juice supplementation and neurocognitive function in human aging. Letenneur L. Risk of dementia and alcohol and wine consumption: A review of recent results. 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The neuroprotective effects of cocoa flavanol and its influence on cognitive performance. British Journal of Clinical Pharmacology. Kawas CH. Medications and diet: Protective factors for AD? Alzheimer Disease and Associated Disorders. Luchsinger JA , Noble JM , Scarmeas N. Current Neurology and Neuroscience Reports. Calon F , Lim GP , Yang F , Morihara T , Teter B , Ubeda O , et al. Calon F , Cole G. Neuroprotective action of omega-3 polyunsaturated fatty acids against neurodegenerative diseases: Evidence from animal studies. Prostaglandins Leukot Essent Fatty Acids. Calon F. Current Alzheimer Research. Vauzour D. Journal of the Science of Food and Agriculture. Foltynie T , Kahan J. J Neurol. Obeso JA , Rodriguez-Oroz MC , Benitez-Temino B , Blesa FJ , Guridi J , Marin C , et al. Movement disorders: Official journal of the Movement Disorder Society. Aarsland D , Tandberg E , Larsen JP , Cummings JL. Frequency of dementia in parkinson disease. Archives of Neurology. Korczyn AD , Reichmann H. Dementia with Lewy bodies. Journal of the Neurological Sciences. Walker Z , Allen RL , Shergill S , Katona CL. The British Journal of Psychiatry. Diagnosis and management of dementia with Lewy bodies: Third report of the DLB Consortium. Boeve BF. Noyce AJ , Bestwick JP , Silveira-Moriyama L , Hawkes CH , Giovannoni G , Lees AJ , et al. Meta-analysis of early nonmotor features and risk factors for Parkinson disease. Annals of Neurology. Van Maele-Fabry G , Hoet P , Vilain F , Lison D. Environment International. de Lau LM , Breteler MM. The Lancet Neurology. Costa J , Lunet N , Santos C , Santos J , Vaz-Carneiro A. Connolly BS , Lang AE. Pharmacological treatment of parkinson disease: A review. Bronstein JM , Tagliati M , Alterman RL , Lozano AM , Volkmann J , Stefani A , et al. Deep brain stimulation for Parkinson disease: An expert consensus and review of key issues. Arch Neurol. Grosso C , Valentão P , Ferreres F , Andrade P. The use of flavonoids in central nervous system disorders. Curr Med Chem. Blanchet J , Longpré F , Bureau G , Morissette M , DiPaolo T , Bronchti G , et al. Resveratrol, a red wine polyphenol, protects dopaminergic neurons in MPTP-treated mice. Progress in Neuro-Psychopharmacology and Biological Psychiatry. Antioxidant Capacity As Influenced by Total Phenolic and Anthocyanin Content, Maturity, and Variety of Vaccinium Species. Goyarzu P , Malin DH , Lau FC , Taglialatela G , Moon WD , Jennings R , et al. Blueberry supplemented diet: Effects on object recognition memory and nuclear factor-kappa B levels in aged rats. Coultrap SJ , Bickford PC , Browning MD. Blueberry-enriched diet ameliorates age-related declines in NMDA receptor-dependent LTP. CyanidinO-galactoside and Blueberry Extracts Supplementation Improves Spatial Memory and Regulates Hippocampal ERK Expression in Senescence-accelerated Mice. Biomedical and Environmental Sciences: BES. Joseph JA , Shukitt-Hale B , Denisova NA , Bielinski D , Martin A , McEwen JJ , et al. Reversals of age-related declines in neuronal signal transduction, cognitive, and motor behavioral deficits with blueberry, spinach, or strawberry dietary supplementation. The Journal of neuroscience: The Official Journal of the Society for Neuroscience. Dias AS , Porawski M , Alonso M , Marroni N , Collado PS , Gonzalez-Gallego J. Quercetin decreases oxidative stress, NF-kappaB activation, and iNOS overexpression in liver of streptozotocin-induced diabetic rats. Martinez-Florez S , Gutierrez-Fernandez B , Sanchez-Campos S , Gonzalez-Gallego J , Tunon MJ. Quercetin attenuates nuclear factor-kappaB activation and nitric oxide production in interleukin-1beta-activated rat hepatocytes. Joseph JA , Shukitt-Hale B , Denisova NA , Prior RL , Cao G , Martin A , et al. Long-term dietary strawberry, spinach, or vitamin E supplementation retards the onset of age-related neuronal signal-transduction and cognitive behavioral deficits. Shukitt-Hale B , Carey AN , Jenkins D , Rabin BM , Joseph JA. Beneficial effects of fruit extracts on neuronal function and behavior in a rodent model of accelerated aging. Shukitt-Hale B , Carey A , Simon L , Mark DA , Joseph JA. Effects of Concord grape juice on cognitive and motor deficits in aging. Shukitt-Hale B , Cheng V , Joseph JA. Effects of blackberries on motor and cognitive function in aged rats. Shih PH , Chan YC , Liao JW , Wang MF , Yen GC. Antioxidant and cognitive promotion effects of anthocyanin-rich mulberry Morus atropurpurea L. Vogiatzoglou A , Mulligan AA , Luben RN , Lentjes MA , Heiss C , Kelm M , et al. Assessment of the dietary intake of total flavanols, monomeric flavanols, proanthocyanidins and theaflavins in the European Union. Asha Devi S , Sagar Chandrasekar BK , Manjula KR , Ishii N. Grape seed proanthocyanidin lowers brain oxidative stress in adult and middle-aged rats. Experimental Gerontology. Balu M , Sangeetha P , Murali G , Panneerselvam C. Age-related oxidative protein damages in central nervous system of rats: Modulatory role of grape seed extract. International journal of developmental neuroscience: The official Journal of the International Society for Developmental Neuroscience. Devi A , Jolitha AB , Ishii N. Grape seed proanthocyanidin extract GSPE and antioxidant defense in the brain of adult rats. Medical science monitor: International Medical Journal of Experimental and Clinical Research. Rendeiro C , Vauzour D , Rattray M , Waffo-Teguo P , Merillon JM , Butler LT , et al. Dietary levels of pure flavonoids improve spatial memory performance and increase hippocampal brain-derived neurotrophic factor. van Praag H , Lucero MJ , Yeo GW , Stecker K , Heivand N , Zhao C , et al. Plant-derived flavanol - epicatechin enhances angiogenesis and retention of spatial memory in mice. Schroeter H , Bahia P , Spencer JP , Sheppard O , Rattray M , Cadenas E , et al. Journal of Neurochemistry. Spencer JP , Schroeter H , Kuhnle G , Srai SK , Tyrrell RM , Hahn U , et al. The Biochemical Journal. Huang Q , Wu LJ , Tashiro S , Gao HY , Onodera S , Ikejima T. Journal of Pharmacological Sciences. Vafeiadou K , Vauzour D , Lee HY , Rodriguez-Mateos A , Williams RJ , Spencer JP. The citrus flavanone naringenin inhibits inflammatory signalling in glial cells and protects against neuroinflammatory injury. Wang J , Varghese M , Ono K , Yamada M , Levine S , Tzavaras N , et al. Cuevas E , Limón D , Pérez-Severiano F , Díaz A , Ortega L , Zenteno E , et al. Antioxidant effects of Epicatechin on the hippocampal toxicity caused by Amyloid-beta in rats. European Journal of Pharmacology. Ejaz Ahmed M , Khan MM , Javed H , Vaibhav K , Khan A , Tabassum R , et al. Neurochemistry International. Desideri G , Kwik-Uribe C , Grassi D , Necozione S , Ghiadoni L , Mastroiacovo D , et al. Benefits in Cognitive Function, Blood Pressure, and Insulin Resistance Through Cocoa Flavanol Consumption in Elderly Subjects With Mild Cognitive Impairment: The Cocoa, Cognition, and Aging CoCoA Study. Neuroprotective effects of ± -catechin against 1-methylphenyl-1,2,3,6-tetrahydropyridine MPTP -induced dopaminergic neurotoxicity in mice. Neuroscience Letters. Ruan H-l , Yang Y , Zhu X-n , Wang X-l , Chen R-z. Similar potency of catechin and its enantiomers in alleviating 1-methylphenylpyridinium ion cytotoxicity in SH-SY5Y cells. Journal of Pharmacy and Pharmacology. Teixeira MDA , Souza CM , Menezes APF , Carmo MRS , Fonteles AA , Gurgel JP , et al. Catechin attenuates behavioral neurotoxicity induced by 6-OHDA in rats. Pharmacology Biochemistry and Behavior. Del Rio D , Costa LG , Lean ME , Crozier A. Polyphenols and health: What compounds are involved? Nutrition, metabolism, and cardiovascular diseases: NMCD. Absorption and metabolism of anthocyanins in elderly women after consumption of elderberry or blueberry. Barros D , Amaral OB , Izquierdo I , Geracitano L , do Carmo Bassols Raseira M , Henriques AT , et al. Behavioral and genoprotective effects of Vaccinium berries intake in mice. Pharmacology, Biochemistry, and Behavior. Cho J , Kang JS , Long PH , Jing J , Back Y , Chung KS. Antioxidant and memory enhancing effects of purple sweet potato anthocyanin and cordyceps mushroom extract. Archives of Pharmacal Research. Ramirez MR , Izquierdo I , do Carmo Bassols Raseira M , Zuanazzi JA , Barros D , Henriques AT. Effect of lyophilised Vaccinium berries on memory, anxiety and locomotion in adult rats. Pharmacological research: The Official Journal of the Italian Pharmacological Society. Purple sweet potato color ameliorates cognition deficits and attenuates oxidative damage and inflammation in aging mouse brain induced by d-galactose. Papandreou MA , Dimakopoulou A , Linardaki ZI , Cordopatis P , Klimis-Zacas D , Margarity M , et al. Effect of a polyphenol-rich wild blueberry extract on cognitive performance of mice, brain antioxidant markers and acetylcholinesterase activity. Behavioural Brain Research. Rendeiro C , Vauzour D , Kean RJ , Butler LT , Rattray M , Spencer JP , et al. Blueberry supplementation induces spatial memory improvements and region-specific regulation of hippocampal BDNF mRNA expression in young rats. Rendeiro C , Foley A , Lau VC , Ring R , Rodriguez-Mateos A , Vauzour D , et al. A role for hippocampal PSA-NCAM and NMDA-NR2B receptor function in flavonoid-induced spatial memory improvements in young rats. Lau FC , Bielinski DF , Joseph JA. Inhibitory effects of blueberry extract on the production of inflammatory mediators in lipopolysaccharide-activated BV2 microglia. Journal of Neuroscience Research. Tarozzi A , Morroni F , Merlicco A , Bolondi C , Teti G , Falconi M , et al. Neuroprotective effects of cyanidin 3-O-glucopyranoside on amyloid beta 25—35 oligomer-induced toxicity. Hung T-C , Chang T-T , Fan M-J , Lee C-C , Chen CY-C. You can find lignans in flax seeds, cashew nuts, peanuts, sesame seeds, and poppy seeds. The stilbene, resveratrol, is increasing in popularity. Found in dark-skinned fruits such as cherries, cranberries, grapes, and blueberries, resveratrol is also found in onions, peanuts, chocolate, and other dietary sources. Because red wine is made from crushed grapes and people who drink moderate amounts of red wine seem to have a lower risk of heart disease, resveratrol is thought to be responsible for these effects, but there needs to be more research to confirm this. Resveratrol does, however, seem to act as an antioxidant. It also appears to boost the immune system and improve endurance and reduce muscle fatigue by increasing the number of energy-producing mitochondria in muscle cells 3. Resveratrol can also reduce the absorption of sugar by the intestine and inhibit the activity of free fatty acids. Although there are more than 10, different flavonoids, only a handful have been closely studied. Flavonoids serve plants by providing protection against the sun's harmful UV rays, free radicals, viruses, and bacteria. They also regulate gene expression and influence the action of certain enzymes. They do the same things in humans and, if taken as a regular part of the diet, they have been implicated in a reduced risk of cardiovascular disease, cancer, neurodegenerative disorders, and other chronic conditions. You can boost your antioxidant intake with NATURELO Raw Greens Powder , made with a rich variety of whole food greens and herbal extracts. 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Polyphenols and anti-aging -
Besides, the complexity of polyphenol-rich extracts of the whole food product e. fruit blend might be more beneficial to treat skin conditions e. However, highly purified polyphenols are important for the study of biological effects and in unraveling mechanisms of action.
Essentially, clinical studies combining pure polyphenols, polyphenol extracts or polyphenolbased nano-formulations with other modalities e. Encyclopedia Scholarly Community.
Entry Journal Book Video Image About Entry Entry Video Image. Submitted Successfully! Thank you for your contribution! You can also upload a video entry or images related to this topic. Version Summary Created by Modification Content Size Created at Operation 1 The article deals with the importance of polyphenols, natural functional biocompounds, which exert potent antioxidant and anti inflammatory effects on skin, allowing to delay aging appearance.
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Menaa, F. Polyphenols against Skin Aging. Menaa F. Accessed February 15, Menaa, Farid. In Encyclopedia. Copy Citation. Home Entry Topic Review Current: Polyphenols against Skin Aging. This entry is adapted from the peer-reviewed paper Polyphenols Skin Anti-aging Antioxidant Inflammation Cosmetics.
Introduction Aging is associated with a gradual decline of physiological and cognitive functions. Polyphenols Benefits on Skin Aging: An Overview Skin, the largest organ of the body, is the organ in which changes associated with aging are most visible.
Conclution The traditional use of plants in medication e. References E De Luca D'alessandro; S Bonacci; G Giraldi; Aging populations: the health and quality of life of the elderly.. Kenyon C. Nature , , Luigi Fontana; Linda Partridge; Valter D Longo; Extending Healthy Life Span--From Yeast to Humans.
Science , , , Haigis M. Molecular Cell , 40 , Nazif Alic; Linda Partridge; Death and dessert: nutrient signalling pathways and ageing. Current Opinion in Cell Biology , 23 , , Yuqing Dong; Sujay Guha; Xiaoping Sun; Min Cao; Xiaoxia Wang; Sige Zou; Nutraceutical Interventions for Promoting Healthy Aging in Invertebrate Models.
Oxidative Medicine and Cellular Longevity , , , Ichihashi M. Toxicology , , Mukhtar H. Photochemistry and Photobiology , 63 , , Felipe Jiménez; Thomas F. Mitts; Kela Liu; Yanting Wang; Aleksander Hinek; Ellagic and Tannic Acids Protect Newly Synthesized Elastic Fibers from Premature Enzymatic Degradation in Dermal Fibroblast Cultures.
Journal of Investigative Dermatology , , , Peres; V. Terra; F. Guarnier; R. Cecchini; A. Cecchini; Photoaging and chronological aging profile: Understanding oxidation of the skin.
Journal of Photochemistry and Photobiology B: Biology , , , Joi A. Nichols; Santosh K. Katiyar; Skin photoprotection by natural polyphenols: anti-inflammatory, antioxidant and DNA repair mechanisms. Archives of Dermatological Research , , , Daniele Del Rio; L.
Costa; M. Lean; A. Crozier; Polyphenols and health: What compounds are involved?. Nutrition, Metabolism and Cardiovascular Diseases , 20 , , Claudine Manach; Augustin Scalbert; Christine Morand; Christian Rémésy; Liliana Jiménez; Polyphenols: food sources and bioavailability.
The American Journal of Clinical Nutrition , 79 , , It's important to note that polyphenols are not a magical cure for aging, but rather a powerful tool that can complement a healthy lifestyle. Eating a diet rich in fruits, vegetables, and other plant-based foods can provide a wide variety of polyphenols, ensuring that you reap their full anti-aging benefits.
In conclusion, polyphenols are truly remarkable compounds that have the potential to slow down the aging process. From protecting against oxidative stress and reducing inflammation to regulating gene expression and promoting collagen production, polyphenols offer a multitude of benefits for our cellular health and overall well-being.
Curious to know what the research says about polyphenols and their anti-aging potential? Let's take a look! Polyphenols, a diverse group of naturally occurring compounds found in plant-based foods, have gained significant attention in recent years due to their potential health benefits.
Numerous studies have explored the effects of polyphenols on aging and have uncovered some promising findings. Several studies have highlighted the promising effects of polyphenols on aging. For instance, a study published in the Journal of Nutrition found that a diet rich in polyphenols was associated with a lower risk of cardiovascular disease, a common age-related condition.
The researchers observed that individuals who consumed higher amounts of polyphenol-rich foods, such as berries, citrus fruits, and green tea, had a reduced risk of developing cardiovascular issues compared to those with a lower intake. Another study in the Journal of Agricultural and Food Chemistry showed that the consumption of polyphenol-rich foods was linked to improved cognitive function in older adults.
The researchers observed that individuals who regularly consumed foods rich in polyphenols, such as dark chocolate, nuts, and red wine, experienced better memory, attention, and overall cognitive performance compared to those who had a lower intake of these foods.
Furthermore, a study published in the Journal of the American Geriatrics Society found that polyphenols may have potential anti-inflammatory effects, which could contribute to slowing down the aging process. The researchers discovered that individuals who consumed a diet high in polyphenols had lower levels of inflammatory markers in their blood, suggesting that polyphenols may help reduce chronic inflammation, a common characteristic of aging.
While the research on polyphenols and anti-aging is exciting, it's important to acknowledge that more studies are needed to fully understand their effects. The majority of research thus far has been conducted in cells or animals, and more human studies are required to confirm the potential benefits of polyphenols in anti-aging strategies.
Additionally, the specific mechanisms through which polyphenols exert their anti-aging effects are still not fully understood. Further research is needed to unravel the complex interactions between polyphenols and the aging process at a molecular level.
Moreover, the optimal dosage and duration of polyphenol intake for maximum anti-aging benefits remain unclear. It is important to determine the appropriate amount of polyphenols needed to achieve the desired effects without exceeding safe limits.
In conclusion, while the existing research suggests that polyphenols may have significant anti-aging potential, further studies are necessary to fully elucidate their mechanisms of action and establish evidence-based guidelines for their use. Nevertheless, incorporating polyphenol-rich foods into a balanced diet may be a promising strategy to support healthy aging.
Ready to harness the power of polyphenols? Here are some practical tips to help you incorporate these fantastic compounds into your daily diet. One of the easiest ways to increase your polyphenol intake is by eating a variety of colorful fruits and vegetables.
Berries, citrus fruits, dark leafy greens, and colorful spices like turmeric and cinnamon are excellent sources of polyphenols. Additionally, incorporating foods like tea, dark chocolate, and red wine in moderation can also boost your polyphenol intake.
While supplements can be convenient, it's always best to get your polyphenols from natural food sources whenever possible. Whole foods not only provide a wider range of nutrients but also offer a more balanced and synergistic combination of polyphenols.
So, aim to prioritize a rainbow-colored plate and enjoy the delicious flavors of nature's polyphenol-packed gifts. Before you embark on a polyphenol-rich journey, let's address some potential side effects and considerations you should keep in mind.
If you're taking medications, it's always wise to consult with your healthcare provider before significantly increasing your polyphenol consumption.
Some polyphenols may interact with certain medications, potentially affecting their effectiveness. Your doctor can guide you on how to incorporate polyphenols into your diet safely. While polyphenols are generally safe and well-tolerated when consumed through whole foods, consuming very high amounts of certain polyphenols, such as supplements, may cause digestive discomfort in some individuals.
It's best to listen to your body and moderate your intake accordingly. So, there you have it - a comprehensive exploration of the benefits of polyphenols for anti-aging. From their antioxidant powers to their anti-inflammatory effects, these extraordinary compounds have the potential to slow down the aging clock.
So why not start incorporating more polyphenol-rich foods into your daily routine and give your body a vibrant boost on your journey to a more youthful you?
Embrace the power of polyphenols and let them work their magic! Blueberry Tea: Filtered Water, Xylitol, Organic Blueberry Juice Concentrate, Natural Blueberry Essence, Organic and Natural Flavors, Natural Raspberry Extract, Organic Fair Trade White Tea Extract, Organic Lemon Juice Concentrate, Turmacin®, Organic Elderberry Extract, Green Tea Extract, Trans-pTerostilbene, Organic Stevia, Vitamin D3.
Clinical and animal studies clearly show that regulating the diet and meal frequency, as well as the application of fasting patterns, such as intermittent, regular or long-term fasting, extends life and healthy longevity and enhances intrinsic defenses against oxidative and metabolic stress.
It also improves cognitive performance and reduces the cardiovascular risk of obesity and obese people. The most persuasive and widely studied intervention is CR.
CR, reducing calorie intake without causing malnutrition, is one of the best ways to extend the lifespan of model organisms and resist age-related diseases. Polyphenols affect specific cellular signaling pathways regulated by CR such as the AMPK signaling pathway and are implicated in the anti-aging process in humans.
CR, often considered a quantitative and the most widely studied intervention, has been shown to delay aging and increase healthy lifespan and longevity in many species. Although it is difficult to implement in the body, CR is the most promising anti-aging intervention.
Healthy aging and human longevity are complex phenotypes influenced by environmental factors, such as physical exercise, diet, health habits and psychosocial status, and genetic factors. Diet and CR play a crucial role in healthy aging. In recent years, the control of molecular mechanisms associated with age-related progression through external intervention of polyphenols an epigenetic regulation of diet has received great attention.
Natural products regulate cell longevity through post-translational modifications of histones and can also induce the upregulation of autophagy, reducing acetyl coenzyme A AccoA levels. In addition, the effects of CR on cancer-related chronic inflammation are of important significance for aging.
Polyphenols commonly found in fruits and vegetables have emerged as well-tolerated simulators of Cr targeting mitochondrial renewal.
elegans and Drosophila melanogaster and extends the lifespan of these animals without reducing fecundity. In summary, the increase in life expectancy increases the incidence of age-related diseases beyond social and economic sustainability.
Therefore, there is an urgent need for interventions that can reverse or at least prevent pathogenic age-related deterioration. Permanently or regularly reducing calorie intake without malnutrition CR and fasting is the only strategy to reliably extend a healthy lifespan in mammals including non-human primates.
Dietary polyphenols as calorie restriction simulators CRMs will become an important part of the pharmacological arsenal against aging.
Both insulin and organismal metabolism pathways are nutrient and energy-dependent signaling pathways, and they are closely associated with AMPK.
AMPK is a major nutrient sensor that acts as a downstream element in life-prolonging interventions, such as dietary restriction, to control the physiological processes of cells and aging. The most powerful and widely studied intervention is CR, and protein restriction and restriction of various amino acids methionine, tryptophan have also been shown to delay aging.
Nutritional geometry provides a new perspective on the relationship between nutrition and aging by focusing on calories, macronutrients and their interactions throughout the dietary domain and considering compensatory feeding in a haphazard feeding experiment.
Such studies in insects and mice have shown that a low-protein, high-carbohydrate diet is associated with the longest lifespan in randomly fed animals.
In addition, DR is one of the main experimental paradigms for studying the mechanism of longevity and aging. The emergence of the Nutritional Geometry Framework GFN has refocused interest from calories to dietary macronutrients. GFN experiments show that longevity and fertility are separated in the trophic space, causing a functional trade-off between the two traits.
Interference with protein deposition, particularly the ability to remove misfolded proteins or protein aggregates, can extend the healthy lifespan of invertebrates and mammals. The AMPK signaling pathway is closely associated with protein homeostasis increased protein stability and removal of damaged proteins through proteasomal degradation or autophagy , mitochondrial biogenesis control of mitochondrial redox homeostasis , and prevention of cell senescence.
Mitochondria can remain healthy by activating processes involved in the life-regulation pathway, including mitosis, mitochondrial division, and fusion. Reduced mitochondrial function is closely related to aging. Mitochondrial DNA damage mtDNA continues to be exposed to reactive oxygen species.
Reduced mitochondrial function leads to decreased ATP synthesis through mitochondrial oxidative phosphorylation OxPHOS , causing ROS production mainly in respiratory complexes I NADH dehydrogenase and III ubiquitin-cytochrome C reductase. Therefore, AMPK may represent as a metabolic target that ameliorates mitochondrial dysfunction with age.
The protective effect of RSV on mitochondrial function has been well showed, and it is mainly mediated by the activation of SIRT1 and the subsequent deacetylation activation of PGC-1α, causing the improvement of mitochondrial biogenesis and function and the increase of antioxidant enzyme expression.
RSV has been shown to extend the lifespan of mice on a high-calorie diet, which is associated with improved insulin sensitivity and an increased expression of AMPK and PGC-1α.
In older subjects, resveratrol has also been shown to improve vascular function and mitochondrial quality. AMPK is a major regulator of metabolic activity. Its activation enhances sirtuin activity. These include peroxisome proliferator-activated receptor-γ coactivator 1alpha and FoxO1 and FoxO3a transcription factors.
AMPK-induced SIRT1-mediated deacetylation of these targets facilitates many of the converging biological effects of AMPK and SIRT1 on energy metabolism.
Luteolin is a flavonoid with a variety of biological properties, including antioxidant activity, inhibition of apoptosis and regulation of autophagy.
Luteolin enhances the scavenging of oxygen free radicals and the activity of SOD in mitochondria. In addition, it can enhance antioxidant capacity by reversing mitochondrial swelling and mitochondrial transmembrane potential. Luteolin can also increase the targeted expression of SIRT3 in mitochondria, decrease the phosphorylation of AMPK, and increase the level of phosphor-mTOR p-mTOR.
Dietary polyphenols act as CR mimetics associated with SIRT1 by modulating the ratio of NAD to NADH and the changes in mitochondrial respiratory activity. They may be involved in structural elements that regulate nicotinamide adenine dinucleotide phosphate NADPH oxidase activity and expression, and thus the most effective interventions for healthy aging include the AMPK signaling pathway.
However, DNA damage and oxidative stress that occur during aging can cause the accumulation of senescent cells, which have harmful effects on multiple organs and systemic functions through SASP. The aging process deteriorates body functions at multiple levels, causing a gradual decline in the ability to resist stress, injury and disease.
By enforcing growth arrest, senescence limits the replication of old or damaged cells. In addition to exiting the cell cycle, senescent cells undergo many other phenotypic changes, such as metabolic reprogramming, chromatin rearrangement, or autophagy regulation.
Senescent cells have been proposed as targets for interventions to delay senescence and its related diseases or to improve the treatment of diseases. Therapeutic interventions with senescent cells may help restore health and cure diseases that share basic processes, rather than curing each disease in a separate and symptomatic manner.
Aging is considered a dynamic process, which means the properties of senescent cells constantly evolve and depend on the cell type. The most common characteristics of senescent cells are enlarged and flattened morphology, less regular shape, larger nuclei, single and larger nucleoli, more vacuoles in the cytoplasm, accumulation of lipofuscin in their lysosomes, increased ROS, and increased lysosomal activity.
One of the key drivers of aging is cellular senescence, which is a state of irreversible growth arrest induced by many pro-tumor stresses. Senescent cells accumulate at the late stage of life and at the site of age-related lesions, causing the onset and progression of disease through complex cellular and acellular autonomic effects.
Cellular senescence is a state of cell cycle stagnation, accompanied by the inhibition of apoptosis and the secretion of a variety of bioactive factors such as SASP , which plays an important physiological role in multiple organs and systemic functions.
A key feature of cellular senescence is stagnation of the cell cycle, activated by age-related stress, such as telomere shortening and oxidative stress.
Excessive accumulation of senescent cells plays an important role in the development of age-related diseases and other age-related morphological and physiological changes.
Therefore, the goal of many researchers is to find a way to eliminate senescent cells and improve the health of older people. Senescent cells are resistant to apoptosis and exhibit SASP, which includes secretion of various pro-inflammatory cytokines, chemokines, proteases, and growth factors.
Senescent cells are more abundant in tissues that suffer from a variety of age-related diseases. Therefore, the use of dietary polyphenols to selectively target these senescent cells could be a promising strategy for anti-aging treatment or improving healthy longevity. Natural polyphenolic products such as astragalus, flavonoids, and chalconone were shown to be effective at ameliorating a variety of age-related phenotypes, including oxidative stress, inflammation, impaired protein homeostasis, and cell senescence in vitro and in vivo.
Resveratrol attenuates the typical aging changes of cell morphology, senescence-related β-galactosidase activity and cell proliferation. The mechanisms involved in this anti-aging effect seem to be independent of the regulation of senescence related genes and proteins but depend on the improvement of protein homeostasis in cells.
Of the 10 flavonoids tested, fisetin was the most effective anti-aging agent. Acute or intermittent treatment with fisetin in presenile and elderly mice reduced the markers of aging in multiple tissues. Fisetin administration at a late stage of life in wild-type mice restored tissue homeostasis, reduced age-related pathology, and extended mean and maximum lifespan.
The senescent cells exhibit metabolic imbalance, which is associated with reduced glycolysis and significantly reduced levels of ribonucleotide triphosphate including ATP.
The depletion of adenosine triphosphate causes an increase in cellular adenosine, which activates AMPK and contributes to the establishment of aging. In a word, getting proper nutrition by harnessing the hormonal effects of dietary polyphenols is an exciting finding and there are still many unexplored areas in the prevention of ageing.
Although many natural polyphenols are being investigated as possible modulators of the AMPK pathway, it remains unclear whether extensive long-term clinical trials are required to determine the long-term benefits of natural polyphenols in delaying aging and age-related diseases. Future clinical studies evaluating the relationship between polyphenols, aging, and AMPK signaling could enrich the knowledge of aging research strategies through epidemiological studies and clinical trials, as well as promising epigenetic and interaction tools, and thus, reveal the true significance of dietary polyphenols as anti-aging compounds in humans.
A better perspective is provided by understanding the contribution of signaling to the health benefits of polyphenols in delaying aging and promoting human health and longevity. Furthermore, with the aim of revealing the specific roles of natural polyphenols in aging and AMPK signaling, we understood the key pathways of aging in greater detail than ever before, with more targets and a richer source of natural dietary polyphenols to better develop the next generation of anti-aging treatments.
In conclusion, dietary polyphenols play an important role in human daily life. Dietary patterns and specific nutritional supplements can play an important role in promoting human health and longevity, paving the way for longer lifespans and slower onset of age-related diseases.
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