Targeting cellular senescence with senotherapeutics: senolytics and senomorphics

FEBS Journal, Год журнала: 2022, Номер 290(5), С. 1362 - 1383

Опубликована: Янв. 11, 2022

The concept of geroscience is that since ageing the greatest risk factor for many diseases and conditions, targeting process itself will have impact on human health. Of hallmarks ageing, cellular senescence has emerged as a druggable therapeutic target extending healthspan in model organisms. Cellular cell state irreversible proliferative arrest driven by different types stress, including oncogene‐induced stress. Many senescent cells (SnCs) develop senescent‐associated secretory phenotype (SASP) comprising pro‐inflammatory cytokines, chemokines, proteases, bioactive lipids, inhibitory molecules, extracellular vesicles, metabolites, lipids other factors, able to promote chronic inflammation tissue dysfunction. SnCs up‐regulate anti‐apoptotic pathways (SCAPs) prevent them from dying despite accumulation damage DNA organelles. These SCAPs altered represent targets development senotherapeutic drugs induce selective death SnCs, specifically termed senolytics or suppress markers senescence, particular SASP, senomorphics. Here, we review current senomorphics treatment age‐related disorders extension healthy longevity. In addition, challenges documenting senolytic senomorphic activity pre‐clinical models clinical application senotherapeutics be discussed.

Язык: Английский

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Plant Phenolics: Bioavailability as a Key Determinant of Their Potential Health-Promoting Applications

Antioxidants, Год журнала: 2020, Номер 9(12), С. 1263 - 1263

Опубликована: Дек. 12, 2020

Phenolic compounds are secondary metabolites widely spread throughout the plant kingdom that can be categorized as flavonoids and non-flavonoids. Interest in phenolic has dramatically increased during last decade due to their biological effects promising therapeutic applications. In this review, we discuss importance of compounds’ bioavailability accomplish physiological functions, highlight main factors affecting such parameter metabolism phenolics, from absorption excretion. Besides, give an updated overview health benefits compounds, which mainly linked both direct (e.g., free-radical scavenging ability) indirect by stimulating activity antioxidant enzymes) properties. Such actions reportedly help them prevent chronic oxidative stress-related disorders cancer, cardiovascular neurodegenerative diseases, among others. Last, comment on development cutting-edge delivery systems intended improve enhance stability human body.

Язык: Английский

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Anti-Obesity Effects of Polyphenol Intake: Current Status and Future Possibilities

International Journal of Molecular Sciences, Год журнала: 2020, Номер 21(16), С. 5642 - 5642

Опубликована: Авг. 6, 2020

The prevalence of obesity has steadily increased worldwide over the past three decades. conventional approaches to prevent or treat this syndrome and its associated complications include a balanced diet, an increase energy expenditure, lifestyle modification. Multiple pharmacological non-pharmacological interventions have been developed with aim improving complications. Recently, use functional foods their bioactive components is considered new approach in prevention management disease. Due biological properties, polyphenols may be as nutraceuticals food supplement recommended for different syndromes. Polyphenols are class naturally-occurring phytochemicals, some which shown modulate physiological molecular pathways involved metabolism. could act stimulation β-oxidation, adipocyte differentiation inhibition, counteract oxidative stress, etc. In narrative review, we association between (resveratrol, quercetin, curcumin, polyphenolic extracts) obesity, focusing on human trials. health effects depend amount consumed bioavailability. Some results contrasting, probably due various study designs lengths, variation among subjects (age, gender, ethnicity), chemical forms dietary used. But, conclusion, data so far obtained encourage setting trials, necessary validate benefic role obese individuals.

Язык: Английский

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Mediterranean Diet as an Antioxidant: The Impact on Metabolic Health and Overall Wellbeing

Nutrients, Год журнала: 2021, Номер 13(6), С. 1951 - 1951

Опубликована: Июнь 6, 2021

It has been established, worldwide, that non-communicable diseases such as obesity, diabetes, metabolic syndrome, and cardiovascular events account for a high percentage of morbidity mortality in contemporary societies. Several modifiable risk factors, sedentary activities, sleep deprivation, smoking, unhealthy dietary habits have contributed to this increase. Healthy nutrition terms adherence the Mediterranean diet (MD), rich fruits, legumes, vegetables, olive oil, herbs, spices, fiber intake may contribute decrease pandemic. The beneficial effects MD can be mainly attributed its numerous components anti-inflammatory antioxidant properties. Moreover, further improvement reproductive health, modify neurodegenerative diseases, protect against depression psychosocial maladjustment. There is also evidence highlighting impact healthy female people on composition gut microbiota future overall health their offspring. therefore important highlight metabolic, reproductive, mental while shaping generations. enhanced by increased physical activity context well-balanced lifestyle.

Язык: Английский

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Stilbenes: Source plants, chemistry, biosynthesis, pharmacology, application and problems related to their clinical Application-A comprehensive review

Phytochemistry, Год журнала: 2022, Номер 197, С. 113128 - 113128

Опубликована: Фев. 17, 2022

Язык: Английский

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Epigenetics in NAFLD/NASH: Targets and therapy

Pharmacological Research, Год журнала: 2021, Номер 167, С. 105484 - 105484

Опубликована: Март 24, 2021

Язык: Английский

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Plant Polyphenols and Their Potential Benefits on Cardiovascular Health: A Review

Molecules, Год журнала: 2023, Номер 28(17), С. 6403 - 6403

Опубликована: Сен. 1, 2023

Fruits, vegetables, and other food items contain phytochemicals or secondary metabolites which may be considered non-essential nutrients but have medicinal importance. These dietary exhibit chemopreventive therapeutic effects against numerous diseases. Polyphenols are found in fruits, grains. compounds several health benefits such as immune modulators, vasodilators, antioxidants. This review focuses on recent studies using polyphenols to treat cardiovascular disorders, atherosclerosis, vascular endothelium deficits. We focus exploring the safety of highly effective ensure their maximum impact cardiac abnormalities discuss epidemiological evidence intervention trials related these properties. Kaempferol, quercetin, resveratrol prevent oxidative stress by regulating proteins that induce oxidation heart tissues. In addition, modulate tone vessels releasing nitric oxide (NO) reducing low-density lipoprotein (LDL) atherosclerosis. cardiomyocytes, suppress expression inflammatory markers inhibit production inflammation exert an anti-inflammatory response. Consequently, diseases strokes, hypertension, failure, ischemic disease could prevented polyphenols.

Язык: Английский

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Kaempferol Can Reverse the 5-Fu Resistance of Colorectal Cancer Cells by Inhibiting PKM2-Mediated Glycolysis

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(7), С. 3544 - 3544

Опубликована: Март 24, 2022

Resistance to 5-Fluorouracil (5-Fu) chemotherapy is the main cause of treatment failure in cure colon cancer. Therefore, there an urgent need explore a safe and effective multidrug resistance reversal agent for colorectal cancer, which would be great significance improving clinical efficacy. The dietary flavonoid kaempferol plays key role progression cancer 5-Fu resistance. However, molecular mechanism reversing human cells still unclear. We found that could reverse drug HCT8-R 5-Fu, suggesting alone or combination with has potential treat It well known aerobic glycolysis related tumor growth Indeed, significantly reduced glucose uptake lactic acid production drug-resistant cells. In terms mechanism, promotes expression microRNA-326 (miR-326) cells, miR-326 inhibit process by directly targeting pyruvate kinase M2 isoform (PKM2) 3'-UTR (untranslated region) PKM2 indirectly block alternative splicing factors PKM mRNA, then 5-Fu. Taken together, our data suggest may play important overcoming therapy regulating miR-326-hnRNPA1/A2/PTBP1-PKM2 axis.

Язык: Английский

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Resveratrol and Immune Cells: A Link to Improve Human Health

Molecules, Год журнала: 2022, Номер 27(2), С. 424 - 424

Опубликована: Янв. 10, 2022

The use of polyphenols as adjuvants in lowering risk factors for various debilitating diseases has been investigated recent years due to their possible antioxidant action. Polyphenols represent a fascinating and relatively new subject research nutraceuticals nutrition, with interest rapidly expanding since they can help maintain health by controlling metabolism, weight, chronic diseases, cell proliferation. Resveratrol is phenolic compound found mostly the pulp, peels, seeds, stems red grapes. It wide variety biological actions that be used prevent beginning or manage symptoms. influence multiple inflammatory non-inflammatory responses, protecting organs tissues, thanks its interaction immune cells activity on SIRT1. This anti-inflammatory, antioxidant, anti-apoptotic, neuroprotective, cardioprotective, anticancer, antiviral properties, making it potential adjunct traditional pharmaceutical therapy public health. review aims provide comprehensive analysis resveratrol terms active effects mechanism action modifying cellular response promote human psychophysical

Язык: Английский

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Benefits and Implications of Resveratrol Supplementation on Microbiota Modulations: A Systematic Review of the Literature

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(7), С. 4027 - 4027

Опубликована: Апрель 5, 2022

Resveratrol is a polyphenol that has been shown to possess many applications in different fields of medicine. This systematic review drawn attention the axis between resveratrol and human microbiota, which plays key role maintaining an adequate immune response can lead diseases when compromised. also be asset new technologies, such as gene therapy. PubMed, Cochrane Library, Scopus, Web Science, Google Scholar were searched find papers matched our topic dating from 1 January 2017 up 18 2022, with English-language restriction using following Boolean keywords: (“resveratrol” AND “microbio*”). Eighteen studies included relevant matching purpose investigation. Immune response, prevention thrombotic complications, therapy, bone regeneration retrieved main topics. The analyzed mostly involved supplementation its effects on microbiota by trials vitro, vivo, ex vivo. beneficial activity evident analyzing changes host’s genetic expression gastrointestinal microbial community administration. possibility identifying individual families may allow tailor therapeutic plans targeted polyphenolic diets associated dysbiosis, inflammatory tract, degenerative diseases, tumors, obesity, diabetes, tissue regeneration, metabolic syndrome.

Язык: Английский

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