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1.
J Nat Med ; 78(3): 576-589, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38662301

RESUMO

This study aimed to compare fat accumulation in young and aged mice raised on a high-fat diet and to characterize the obesity-reducing effects of a Kampo medicine, bofutsushosan (BTS; fangfengtongshengsan in Chinese). Aged mice fed a high-fat diet containing 2% BTS extract for 28 days exhibited a significant reduction in weight gain and accumulation of visceral and subcutaneous fat, which were greater degree of reduction than those of the young mice. When the treatment period was extended to two months, the serum aspartate aminotransferase and alanine aminotransferase levels and the accumulation of fat droplets in the hepatocytes decreased. The mRNA expression of mitochondrial uncoupling protein 1 (UCP1) in the brown adipose tissue was significantly reduced in the aged mice compared to the young mice but increased by 2% in the BTS-treated aged mice. Additionally, the effect of BTS extract on oleic acid-albumin-induced triglyceride accumulation in hepatoblastoma-derived HepG2 cells was significantly inhibited in a concentration-dependent manner. Evaluation of the single crude drug extracts revealed that Forsythia Fruit, Schizonepeta Spike, and Rhubarb were the active components in BTS extract. These results suggest that BTS extract is effective against visceral, subcutaneous, and ectopic fats in the liver, which tend to accumulate with aging. Thus, BTS extract is useful in preventing and ameliorating the development of obesity and metabolic syndrome.


Assuntos
Envelhecimento , Dieta Hiperlipídica , Medicamentos de Ervas Chinesas , Obesidade , Animais , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Camundongos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Masculino , Dieta Hiperlipídica/efeitos adversos , Envelhecimento/efeitos dos fármacos , Humanos , Células Hep G2 , Camundongos Endogâmicos C57BL , Proteína Desacopladora 1/metabolismo , Triglicerídeos/sangue , Triglicerídeos/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Aspartato Aminotransferases/sangue
3.
Phytother Res ; 38(5): 2347-2360, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38421057

RESUMO

Recently, various studies have shown that epigenetic changes are associated with aging and age-related diseases. Both animal and human models have revealed that epigenetic processes are involved in aging mechanisms. These processes happen at multiple levels and include histone modification, DNA methylation, and changes in noncoding RNA expression. Consequently, changes in the organization of chromatin and DNA accessibility lead to the regulation of gene expression. With increasing awareness of the pivotal function of epigenetics in the aging process, researchers' attention has been drawn to how these epigenetic changes can be modified to prevent, stop, or reverse aging, senescence, and age-related diseases. Among various agents that can affect epigenetic, polyphenols are well-known phytochemicals found in fruits, vegetables, and plants. Polyphenols are found to modify epigenetic-related mechanisms in various diseases and conditions, such as metabolic disorders, obesity, neurodegenerative diseases, cancer, and cardiovascular diseases. Resveratrol (RSV) is a member of the stilbene subgroup of polyphenols which is derived from various plants, such as grapes, apples, and blueberries. Therefore, herein, we aim to summarize how RSV affects different epigenetic processes to change aging-related mechanisms. Furthermore, we discuss its roles in age-related diseases, such as Alzheimer's, Parkinson's, osteoporosis, and cardiovascular diseases.


Assuntos
Envelhecimento , Metilação de DNA , Epigênese Genética , Resveratrol , Resveratrol/farmacologia , Epigênese Genética/efeitos dos fármacos , Humanos , Envelhecimento/efeitos dos fármacos , Metilação de DNA/efeitos dos fármacos , Animais , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/genética , Polifenóis/farmacologia , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/genética
4.
Science ; 380(6649): eabn9257, 2023 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-37289866

RESUMO

Aging is associated with changes in circulating levels of various molecules, some of which remain undefined. We find that concentrations of circulating taurine decline with aging in mice, monkeys, and humans. A reversal of this decline through taurine supplementation increased the health span (the period of healthy living) and life span in mice and health span in monkeys. Mechanistically, taurine reduced cellular senescence, protected against telomerase deficiency, suppressed mitochondrial dysfunction, decreased DNA damage, and attenuated inflammaging. In humans, lower taurine concentrations correlated with several age-related diseases and taurine concentrations increased after acute endurance exercise. Thus, taurine deficiency may be a driver of aging because its reversal increases health span in worms, rodents, and primates and life span in worms and rodents. Clinical trials in humans seem warranted to test whether taurine deficiency might drive aging in humans.


Assuntos
Envelhecimento , Taurina , Animais , Humanos , Camundongos , Envelhecimento/sangue , Envelhecimento/efeitos dos fármacos , Envelhecimento/metabolismo , Senescência Celular , Haplorrinos , Longevidade/efeitos dos fármacos , Longevidade/fisiologia , Taurina/sangue , Taurina/deficiência , Taurina/farmacologia , Suplementos Nutricionais , Dano ao DNA/efeitos dos fármacos , Telomerase/metabolismo
5.
Phytochemistry ; 213: 113751, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37307887

RESUMO

Boswellia dalzielii is a resin-producing tree endemic to West and Central Africa, used by local populations for various medicinal purposes. In this study, B. dalzielii gum resin was analyzed by GC-MS and UHPLC-MS to identify and quantify volatile and non-volatile compounds. Its main volatile constituents were α-pinene (54.9%), followed by α-thujene (4.4%) and α-phellandren-8-ol (4.0%). Pentacyclic triterpenoids such as ß-boswellic acids and their derivatives were quantified by UHPLC-MS and their content was shown to reach around 22% of the gum resin. Since some of the volatile and non-volatile compounds identified in this work are known to possess biological effects, the bioactivities of B. dalzielii ethanolic extract, essential oil, as well as fractions of the oil and extract were evaluated. Some of these samples exhibited interesting anti-inflammatory properties, and their antioxidant, anti-ageing and skin-bleaching activities were also tested.


Assuntos
Boswellia , Compostos Fitoquímicos , Resinas Vegetais , Envelhecimento/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Boswellia/química , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Resinas Vegetais/química , Preparações Clareadoras de Pele/química , Preparações Clareadoras de Pele/farmacologia , Triterpenos/química , Triterpenos/farmacologia
6.
São Paulo; s.n; 2023. 33 p.
Tese em Português | ColecionaSUS, SMS-SP, HSPM-Producao, SMS-SP | ID: biblio-1532794

RESUMO

A dermatoporose é a síndrome de fragilidade cutânea. Acomete principalmente indivíduos acima de 60 anos, com maior prevalência no sexo feminino. Os principais fatores de risco são: envelhecimento, exposição solar intensa e uso de corticoterapia tópica e sistêmica. Se manifesta clinicamente por atrofia cutânea, púrpuras senis, pseudo cicatrizes estrelares e lacerações, podendo evoluir com hematomas dissecantes e infecções graves. Trata-se de uma doença com grande impacto na qualidade de vida dos pacientes e, até o presente momento, não há terapias com resultados satisfatórios. Hidratação, vitamina C tópica e oral, luz intensa pulsada foram algumas das terapêuticas estudadas. A hidroxiapatita de cálcio é um bioestimulador de colágeno composto por microesferas em um veículo de carboximetilcelulose (Radiesse®). Tem sido usada para estimular a produção endógena de colágeno e consequentemente melhorar a qualidade e espessura da pele. Este efeito do produto poderia melhorar o quadro clínico da dermatoporose. O estudo teve como objetivo avaliar a melhora das lesões purpúricas e da atrofia da pele após aplicação de Radiesse® no antebraço de 5 pacientes portadores de dermatoporose no setor de Dermatologia do Hospital do Servidor Público Municipal de São Paulo. Os 5 pacientes foram submetidos a aplicação de Radiesse® nos antebraços e foram avaliadas 45 e 90 dias após o procedimento, o número de lesões purpúricas, grau de atrofia da pele através do teste de pinçamento e realizado comparação fotográfica. Após o tratamento, observou-se melhora do número das lesões purpúricas, melhora da atrofia da pele e melhora da qualidade de pele quando comparada fotograficamente. Dessa forma, o tratamento com Radiesse® mostrou-se promissor, com resultados satisfatórios e com um bom perfil de segurança. Palavras-chave: Dermatoporose. Púrpura senil. Radiesse. Bioestimulador. Tratamento.


Assuntos
Púrpura/tratamento farmacológico , Atrofia/diagnóstico , Pele/efeitos dos fármacos , Dermatopatias/diagnóstico , Envelhecimento/efeitos dos fármacos , Carboximetilcelulose Sódica/administração & dosagem , Envelhecimento da Pele/efeitos dos fármacos , Corticosteroides/efeitos adversos , Desidroepiandrosterona/fisiologia , Durapatita/administração & dosagem , Durapatita/uso terapêutico , Terapia com Luz de Baixa Intensidade
7.
Geriatr Gerontol Int ; 22(5): 433-440, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35352454

RESUMO

AIMS: Aging is a critical contributing factor for cardiovascular diseases. The d-galactose-induced accelerated aging model is comparable to physiological aging from the cellular to the physiological level. The d-galactose treatment induces mitochondrial dysfunction, increased reactive oxygen species (ROS) production, and upregulation of senescence-related genes. Cordycepin, a functional element in Chinese traditional medicine, has multiple beneficial effects as an antioxidant and ROS scavenger, and has been reported to be effective in a number of ischemia models. This paper aims to investigate the cardioprotective effects of cordycepin in the d-galactose accelerated aging model. METHODS: In the current study, we employed the d-galactose accelerated aging model to study the cardioprotective effect of cordycepin. Eight-week-old Sprague-Dawley rats, randomly divided into five groups, were given vehicle, d-galactose (150 mg/kg/day), and cordycepin at 5, 10, and 20 mg/kg per day. At the end of the 8-week treatment, rat cardiac structure and function were assessed with echocardiographic imaging and hemodynamic parameter analysis. RESULTS: Cordycepin upregulated the expression of Klotho in serum and heart tissues. The expressions of senescence markers ß-galactosidase, p21, and oxidative stress marker malondialdehyde (MDA) were downregulated by cordycepin treatment. Reduction of levels and activity of the antioxidant factors superoxide dismutase (SOD) and catalase (CAT) induced by by d-galactose treatment was ameliorated by cordycepin. Furthermore, cordycepin activated AMPK signaling in d-galactose-treated rats. After 8 weeks of treatment, we found that cordycepin improved myocardia contractility and hypertension caused by d-galactose treatment. Mechanistically, reduced expression of the Klotho protein SOD1 caused by d-galactose was recovered in rats co-treated with cordycepin. CONCLUSION: Cordycepin could protect against cardiac dysfunction in a d-galactose-induced aging rat model, suggesting the therapeutic cardioprotective potential of cordycepin in aging. Geriatr Gerontol Int 2022; 22: 433-440.


Assuntos
Envelhecimento , Antioxidantes , Desoxiadenosinas , Animais , Ratos , Envelhecimento/efeitos dos fármacos , Antioxidantes/farmacologia , Desoxiadenosinas/farmacologia , Galactose/toxicidade , Malondialdeído , Estresse Oxidativo , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio
8.
J Ethnopharmacol ; 290: 115110, 2022 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-35181488

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Polyalthia longifolia var. angustifolia Thw. (Annonaceae) is commonly used in traditional medicine as a tonic for rejuvenation and exhibiting good antioxidant activities. AIM OF THE STUDY: To evaluate P. longifolia methanolic leaf extract (PLME) antiaging activity at 1 mg/mL in Saccharomyces cerevisiae BY611 yeast. MATERIALS AND METHODS: The antiaging effect of PLME was studied via replicative lifespan assay, antioxidative stress assays, reactive oxygen species (ROS) determination, reduced glutathione (GSH) determination, superoxide dismutase (SOD) and Sirtuin 1 (SIRT1) genes regulation studies and SOD and SIRT1 proteins activities. RESULTS: The PLME treatment increased the growth and prolonged the lifespan of the yeast significantly (p < 0.05) compared to the untreated yeast group. Besides, the PLME also protected the yeast from oxidative stress induced by 4-mM-H2O2 via decreasing (p < 0.05) the ROS from 143.207 to 127.223. The antioxidative action of PLME was proved by spot assay. Phloxine B staining was further confirmed the PLME antioxidative action of PLME, where more whitish-pink live yeast cells were observed. In addition, the PLME also enhanced GSH content significantly (p < 0.05) in yeast treated with PLME from 16.81 to 25.31 µmol. Furthermore, PLME increased the SOD and SIRT1 genes expression significantly (p < 0.05) with ΔCt values of 1.11 and 1.15, respectively. The significantly (p < 0.05) elevated SOD and SIRT1 protein activities were recorded as 51.54 U/mg Prot and 1716 ng/mL, respectively. CONCLUSIONS: PLME exhibited good antiaging activities in S. cerevisiae, by modulating oxidative stress, enhancing GSH content, and increasing SOD and SIRT1 genes expression.


Assuntos
Envelhecimento/efeitos dos fármacos , Antioxidantes/farmacologia , Extratos Vegetais/farmacologia , Polyalthia/química , Polifenóis/farmacologia , Saccharomyces cerevisiae/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Sirtuína 1/efeitos dos fármacos , Superóxido Dismutase/efeitos dos fármacos
9.
Oxid Med Cell Longev ; 2022: 3644318, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35222795

RESUMO

Reduced testosterone level is a common feature of aging in men. Aging, as a risk factor for several neurodegenerative disorders, shows declined mitochondrial function and downregulated mitochondrial biogenesis and mitochondrial dynamics. Mitochondrial biogenesis and mitochondrial dynamics are crucial in maintaining proper mitochondrial function. Supplementation with testosterone is conducive to improving mitochondrial function of males during aging. Nuclear factor erythroid 2-related factor 2 (Nrf2), a regulator of redox homeostasis, is involved in the ameliorative effects of testosterone supplementation upon aging. To explore Nrf2 role in the effects of testosterone supplementation on mitochondrial function during aging, we studied the efficiency of testosterone supplementation in improving mitochondrial function of Nrf2 knockout- (KO-) aged male mice by analyzing the changes of mitochondrial biogenesis and mitochondrial dynamics. It was found that wild-type- (WT-) aged male mice showed low mitochondrial function and expression levels of PGC-1α, NRF-1\NRF-2, and TFAM regulating mitochondrial biogenesis, as well as Drp1, Mfn1, and OPA1 controlling mitochondrial dynamics in the substantia nigra (SN). Nrf2 KO aggravated the defects above in SN of aged male mice. Testosterone supplementation to WT-aged male mice significantly ameliorated mitochondrial function and upregulated mitochondrial biogenesis and mitochondrial dynamics, which were not shown in Nrf2 KO-aged male mice due to Nrf2 deficiency. Testosterone deficiency by gonadectomy (GDX) decreased mitochondrial function, downregulated mitochondrial biogenesis, and altered mitochondrial dynamics balance in young male mice. Supplementation with testosterone to Nrf2 KO-GDX mice only ameliorated the alterations above but did not reverse them to sham level. Nrf2 deficiency attenuated testosterone efficiency in ameliorating mitochondrial function in the SN of aged male mice through mitochondrial biogenesis and mitochondrial dynamics to some extent. Activation of Nrf2 might contribute to testosterone-upregulating mitochondrial biogenesis and mitochondrial dynamics in the SN during aging to produce efficient mitochondria for ATP production.


Assuntos
Envelhecimento/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/deficiência , Substância Negra/efeitos dos fármacos , Testosterona/farmacologia , Envelhecimento/metabolismo , Animais , Suplementos Nutricionais , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Camundongos Knockout , Mitocôndrias/metabolismo , Dinâmica Mitocondrial/efeitos dos fármacos , Biogênese de Organelas , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Substância Negra/metabolismo , Testosterona/administração & dosagem , Testosterona/deficiência , Caminhada
10.
Life Sci ; 293: 120333, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35051422

RESUMO

Ageing is the most significant risk factor for cardiovascular diseases. l-Carnitine has a potent cardioprotective effect and its synthesis decreases during ageing. At the same time, there are pharmaceuticals, such as mildronate which, on the contrary, are aimed at reducing the concentration of l-carnitine in the heart and lead to slows down the oxidation of fatty acids in mitochondria. Despite this, both l-carnitine and mildronate are positioned as cardio protectors. We showed that l-carnitine supplementation to the diet of 15-month-old mice increased expression of the PGC-1α gene, which is responsible for the regulation of fatty acid oxidation, and the Nrf2 gene, which is responsible for protecting mitochondria by regulating the expression of antioxidants and mitophagy, in the heart. Mildronate activated the expression of genes that regulate glucose metabolism. Probably, this metabolic shift may protect the mitochondria of the heart from the accumulation of acyl-carnitine, which occurs during the oxidation of fatty acids under oxygen deficiency. Both pharmaceuticals impacted the gut microbiome bacterial composition. l-Carnitine increased the level of Lachnoanaerobaculum and [Eubacterium] hallii group, mildronate increased the level of Bifidobacterium, Rikinella, Christensenellaceae. Considered, that these bacteria for protection the organism from various pathogens and chronic inflammation. Thus, we suggested that the positive effects of both drugs on the mitochondria metabolism and gut microbiome bacterial composition may contribute to the protection of the heart during ageing.


Assuntos
Envelhecimento/metabolismo , Fármacos Cardiovasculares/farmacologia , Carnitina/farmacologia , Microbioma Gastrointestinal/fisiologia , Metilidrazinas/farmacologia , Mitocôndrias Cardíacas/metabolismo , Envelhecimento/efeitos dos fármacos , Animais , Bifidobacterium/metabolismo , DNA Mitocondrial/metabolismo , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias Cardíacas/efeitos dos fármacos
11.
Biomed Pharmacother ; 146: 112427, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35062051

RESUMO

Common characteristics of aging include reduced somatic stem cell number, susceptibility to cardiac injuries, metabolic imbalances and increased risk for oncogenesis. In this study, Pleiotropic anti-aging effects of a decoction Jing Si herbal drink (JS) containing eight Traditional Chinese Medicine based herbs, with known effects against aging related disorders was evaluated. Adipose derived mesenchymal stem cells (ADMSCs) from 16 week old adult and 24 month old aging WKY rats were evaluated for the age-related changes in stem cell homeostasis. Effects of JS on self-renewal, klotho and Telomerase Reverse Transcriptase expression DNA damage response were determined by immunofluorescence staining. The effects were confirmed in senescence induced human ADMSCs and in addition, the potential of JS to maintain telomere length was evaluated by qPCR analysis in ADMSCs challenged for long term with doxorubicin. Further, the effects of JS on doxorubicin-induced hypertrophic effect and DNA damage in H9c2 cardiac cells; MPP+-induced damages in SH-SY5Y neuron cells were investigated. In addition, effects of JS in maintaining metabolic regulation, in terms of blood glucose regulation in type-II diabetes mice model, and their potential to suppress malignancy in different cancer cells were ascertained. The results show that JS maintains stem cell homeostasis and provides cytoprotection. In addition JS regulates blood glucose metabolism, enhances autophagic clearances in neurons and suppresses cancer growth and migration. The results show that JS acts on multiple targets and provides a cumulative protective effect against various age-associated disorders and therefore it is a candidate pleiotropic agent for healthy aging.


Assuntos
Envelhecimento/efeitos dos fármacos , Medicamentos de Ervas Chinesas/administração & dosagem , Células-Tronco Mesenquimais/efeitos dos fármacos , Medicina Regenerativa/métodos , Animais , Citoproteção/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Controle Glicêmico/métodos , Humanos , Camundongos , Ratos , Ratos Endogâmicos WKY , Homeostase do Telômero/efeitos dos fármacos
12.
Gene ; 815: 146178, 2022 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-34995733

RESUMO

Frailty develops due to multiple factors, such as sarcopenia, chronic pain, and dementia. Go-sha-jinki-Gan (GJG) is a traditional Japanese herbal medicine used for age-related symptoms. We have reported that GJG improved sarcopenia, chronic pain, and central nervous system function through suppression of tumor necrosis factor-alpha (TNF-α) production. In the present study, GJG was found to reduce the production of TNF-α in the soleus muscle of senescence-accelerated mice at 12 weeks and 36 weeks. GJG did not change the differentiation of C2C12 cells with 2% horse serum. GJG significantly decreased the expression of Muscle atrophy F-box protein (MAFbx) induced by TNF-α in C2C12 cells on real-time PCR. TNF-α significantly decreased the expression of PGC-1α and negated the enhancing effect of GJG for the expression of PGC-1α on digital PCR. Examining 20 chemical compounds derived from GJG, cinnamaldehyde from cinnamon bark and Chikusetsusaponin V (CsV) from Achyrantes Root dose-dependently decreased the production of TNF-⍺ in RAW264.7 cells stimulated by LPS. CsV inhibited the nuclear translocation of nuclear factor-kappa B (NF-κB) p65 in RAW264.7 cells. CsV showed low permeability using Caco-2 cells. However, the plasma concentration of CsV was detected from 30 min to 6 h and peaked at 1 h in the CD1 (ICR) mice after a single dose of GJG. In 8-week-old SAMP8 mice fed 4% (w/w) GJG from one week to four weeks, the plasma CsV concentration ranged from 0.0500 to 10.0 ng/mL. The evidence that CsV plays an important role in various anti-aging effects of GJG via suppression of TNF-⍺ expression is presented.


Assuntos
Envelhecimento/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Saponinas/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Administração Oral , Animais , Relação Dose-Resposta a Droga , Estabilidade de Medicamentos , Medicamentos de Ervas Chinesas/química , Masculino , Camundongos , Camundongos Endogâmicos ICR , Proteínas Musculares/metabolismo , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Células RAW 264.7 , Proteínas Ligases SKP Culina F-Box/metabolismo , Saponinas/administração & dosagem , Saponinas/sangue , Solubilidade , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/farmacologia
13.
Neurobiol Aging ; 109: 113-124, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34715442

RESUMO

Layer 3 (L3) pyramidal neurons in aged rhesus monkey lateral prefrontal cortex (LPFC) exhibit significantly elevated excitability in vitro and reduced spine density compared to neurons in young subjects. The time-course of these alterations, and whether they can be ameliorated in middle age by the powerful anti-oxidant curcumin is unknown. We compared the properties of L3 pyramidal neurons from the LPFC of behaviorally characterized rhesus monkeys over the adult lifespan using whole-cell patch clamp recordings and neuronal reconstructions. Working memory (WM) impairment, neuronal hyperexcitability, and spine loss began in middle age. There was no significant relationship between neuronal properties and WM performance. Middle-aged subjects given curcumin exhibited better WM performance and less neuronal excitability compared to control subjects. These findings suggest that the appropriate time frame for intervention for age-related cognitive changes is early middle age, and points to the efficacy of curcumin in delaying WM decline. Because there was no relationship between excitability and behavior, the effects of curcumin on these measures appear to be independent.


Assuntos
Envelhecimento/efeitos dos fármacos , Envelhecimento/patologia , Curcumina/administração & dosagem , Curcumina/farmacologia , Suplementos Nutricionais , Memória de Curto Prazo/efeitos dos fármacos , Memória de Curto Prazo/fisiologia , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/patologia , Células Piramidais/efeitos dos fármacos , Células Piramidais/patologia , Fatores Etários , Envelhecimento/psicologia , Animais , Feminino , Macaca mulatta , Masculino , Técnicas de Patch-Clamp , Células Piramidais/fisiologia , Fatores de Tempo
14.
J Ethnopharmacol ; 282: 114653, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-34547420

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: BaZiBuShen formula (BZBS) is clinically used to counteract mental fatigue and to retard the aging process. Brain aging echoes in major risks of human sufferings and has become one of the main challenges to our societies and the health-care systems. AIM OF THE STUDY: To investigate the effect and mode of action of BZBS on aging-associated cognitive impairments. MATERIALS AND METHODS: BZBS was orally administered to D-galactose and NaNO2-induced aging mice. Premature senescence was assessed using the Morris water maze, step-down type passive avoidance, and pole-climbing tests. Telomere length was examined by qPCR analysis. Telomerase activity was assessed using PCR ELISA assay. Mitochondrial complex IV activity was examined by biochemical test. The levels of redox and immune status were determined by ELISA or biochemical assay. The expressions of sirtuin 6 (Sirt6), peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), P53, telomerase reverse transcriptase (TERT), heme oxygenase-1 (HO-1), phospho(p)-nuclear factor erythroid-2 related factor 2 (NRF2), caspase-3, Bcl-2 associated x (Bax), and B-cell lymphoma-2 (Bcl-2) in the cerebral cortex were examined by Western blot and/or immunohistochemical staining. RESULTS: BZBS intervention ameliorated reduced brain performances in aging mice, including memory, cognitive, and motor functions. In addition, BZBS administration to aging mice preserved redox homeostasis, attenuated immunosenescence, and maintained telomerase activity and telomere length. Moreover, BZBS treatment were associated with a declines in P53, caspase-3, Bax expressions and an increase in Sirt6, p-HO-1, p-NRF2, PGC-1α, and Bcl-2 expressions in the brains of this rapid aging mouse. CONCLUSIONS: BZBS attenuates premature senescence possibly via the preservation of redox homeostasis and telomere integrity, and inhibition of apoptosis in rapid aging mouse. The mechanism governing the alterations may be associated with through the activation of Sirt6/NRF2/HO-1 and Sirt6/P53-PGC-1α-TERT signaling pathways. The results suggest that BZBS may provide a novel strategy for confronting aging and age-associated diseases.


Assuntos
Medicamentos de Ervas Chinesas , Heme Oxigenase-1 , Proteínas de Membrana , Fator 2 Relacionado a NF-E2 , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Sirtuínas , Telomerase , Proteína Supressora de Tumor p53 , Animais , Masculino , Camundongos , Envelhecimento/efeitos dos fármacos , Envelhecimento/fisiologia , Proliferação de Células/efeitos dos fármacos , Disfunção Cognitiva/tratamento farmacológico , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Linfócitos/efeitos dos fármacos , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/fisiologia , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Transtornos da Memória/tratamento farmacológico , Camundongos Endogâmicos ICR , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Sirtuínas/genética , Sirtuínas/metabolismo , Telomerase/genética , Telomerase/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
15.
Food Funct ; 13(1): 121-130, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34897342

RESUMO

Mogroside-rich extract (MGE), the main bioactive component of dried Siraitia grosvenorii fruit, has long been used as a natural sweetener and traditional Chinese medicine. This extract possesses various types of pharmacological activities, such as anti-inflammatory, antioxidative, hypoglycemic and hypolipemic activities. Moreover, we recently revealed that MGE has beneficial effects on female reproduction. Increasing maternal age leads to a rapid reduction in female fertility; in particular, it dramatically decreases ovarian function. Nevertheless, whether MGE can alleviate ovarian aging and the underlying mechanisms have not yet been explored. In this study, mice were treated with MGE by supplementation in drinking water from 10 to 44 weeks of age. Then, ovarian function and molecular changes were determined. Our findings showed that MGE treatment protected aged mice from estrous cycle disorder. Moreover, MGE treatment significantly increased the ovarian reserves of aged mice. RNA-seq data showed that MGE upregulated the expression of genes related to gonad development, follicular development, and hormone secretion in ovarian tissue. Additionally, inflammatory stress was induced, as indicated by upregulation of inflammation-related gene expression and elevated TNF-α levels in the ovarian tissues of aged mice; however, MGE treatment attenuated inflammatory stress. In summary, our findings demonstrate that MGE can ameliorate age-related estrous cycle disorder and ovarian reserve decline in mice, possibly by alleviating ovarian inflammatory stress.


Assuntos
Anti-Inflamatórios , Cucurbitaceae/química , Reserva Ovariana/efeitos dos fármacos , Extratos Vegetais , Triterpenos , Envelhecimento/efeitos dos fármacos , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Feminino , Inflamação/metabolismo , Camundongos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Estresse Fisiológico/efeitos dos fármacos , Triterpenos/química , Triterpenos/farmacologia
16.
Carbohydr Polym ; 277: 118824, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34893241

RESUMO

Polysaccharides are macromolecules with important inherent properties and potential biotechnological applications. These complex carbohydrates exist throughout nature, especially in plants, from which they can be obtained with high yields. Different extraction and purification methods may affect the structure of polysaccharides and, due to the close relationship between structure and function, modify their biological activities. One of the possible applications of these polysaccharides is acting on the skin, which is the largest organ in the human body and can be aged by intrinsic and extrinsic processes. Skincare has been gaining worldwide attention not only to prevent diseases but also to promote rejuvenation in aesthetic treatments. In this review, we discussed the polysaccharides obtained from plants and their innovative potential for skin applications, for example as wound-healing, antimicrobial, antioxidant and anti-inflammatory, antitumoral, and anti-aging compounds.


Assuntos
Antibacterianos/farmacologia , Anti-Inflamatórios/farmacologia , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Neoplasias/tratamento farmacológico , Polissacarídeos/farmacologia , Envelhecimento/efeitos dos fármacos , Antibacterianos/química , Antibacterianos/isolamento & purificação , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Bactérias/efeitos dos fármacos , Humanos , Plantas Medicinais/química , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Higiene da Pele , Cicatrização/efeitos dos fármacos
17.
Nutrients ; 13(12)2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34959868

RESUMO

Declines in physiological functions are the predominant risk factors for age-related diseases, such as cancers and neurodegenerative diseases. Therefore, delaying the aging process is believed to be beneficial in preventing the onset of age-related diseases. Previous studies have demonstrated that Graptopetalum paraguayense (GP) extract inhibits liver cancer cell growth and reduces the pathological phenotypes of Alzheimer's disease (AD) in patient IPS-derived neurons. Here, we show that GP extract suppresses ß-amyloid pathology in SH-SYS5Y-APP695 cells and APP/PS1 mice. Moreover, AMP-activated protein kinase (AMPK) activity is enhanced by GP extract in U87 cells and APP/PS1 mice. Intriguingly, GP extract enhances autophagy in SH-SYS5Y-APP695 cells, U87 cells, and the nematode Caenorhabditis elegans, suggesting a conserved molecular mechanism by which GP extract might regulate autophagy. In agreement with its role as an autophagy activator, GP extract markedly diminishes mobility decline in polyglutamine Q35 mutants and aged wild-type N2 animals in C. elegans. Furthermore, GP extract significantly extends lifespan in C. elegans.


Assuntos
Envelhecimento/efeitos dos fármacos , Crassulaceae/química , Extratos Vegetais/farmacologia , Proteínas Quinases Ativadas por AMP/efeitos dos fármacos , Peptídeos beta-Amiloides/efeitos dos fármacos , Animais , Autofagia/efeitos dos fármacos , Caenorhabditis elegans/efeitos dos fármacos , Técnicas de Cultura de Células , Modelos Animais de Doenças , Humanos , Longevidade/efeitos dos fármacos , Camundongos , Camundongos Transgênicos
18.
Aging (Albany NY) ; 13(22): 24485-24499, 2021 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-34847066

RESUMO

The search continues for possible interventions that delay and/or reverse biological aging, resulting in extended healthspan and lifespan. Interventions delaying aging in animal models are well established; however, most lack validation in humans. The length of human lifespan makes it impractical to perform survival analysis. Instead, aging biomarkers, such as DNA methylation (DNAm) clocks, have been developed to monitor biological age. Herein we report a retrospective analysis of DNA methylation age in 42 individuals taking Rejuvant®, an alpha-ketoglutarate based formulation, for an average period of 7 months. DNAm testing was performed at baseline and by the end of treatment with Rejuvant® supplementation. Remarkably, individuals showed an average decrease in biological aging of 8 years (p-value=6.538x10-12). Furthermore, the supplementation with Rejuvant® is robust to individual differences, as indicated by the fact that a large majority of participants decreased their biological age. Moreover, we found that Rejuvant® is of additional benefit to chronologically and biologically older individuals. While continued testing, particularly in a placebo-controlled design, is required, the nearly 8-year reversal in the biological age of individuals taking Rejuvant® for 4 to 10 months is noteworthy, making the natural product cocktail an intriguing candidate to affect human aging.


Assuntos
Envelhecimento/efeitos dos fármacos , Suplementos Nutricionais , Ácidos Cetoglutáricos , Vitaminas , Adulto , Idoso , Metilação de DNA/efeitos dos fármacos , Feminino , Gerociência , Humanos , Masculino , Pessoa de Meia-Idade
19.
Food Funct ; 12(24): 12395-12406, 2021 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-34812833

RESUMO

Ginkgo seeds are a traditional food in China valued for their nutritional and health benefits. However, little is known about the anti-aging and health-promoting effects of ginkgo seed products. Here, we showed that ginkgo seed powder extract (GSP-E) is abundant in alkaloids and flavonoids, and can extend the lifespan of Caenorhabditis elegans. GSP-E improved most physiological indicators related to aging of C. elegans, including locomotor activity, reproductive capacity, and resistance to oxidation and heat. Moreover, GSP-E reduced the accumulation of lipofuscin and reactive oxygen species (ROS) in C. elegans. Further studies demonstrated that GSP-E improved longevity and stress resistance by mediating lipid metabolism and autophagy, as well as by regulating gene expression (e.g., FASN-1, POD-2, GPX-7, FAT-5). GSP-E has an anti-amyloid effect and delayed amyloid-induced paralysis of C. elegans. These findings could support the utilization of ginkgo seed as a potential dietary supplement for the health food industry, and provide a novel health-promoting resource against aging and aging-related diseases.


Assuntos
Envelhecimento/efeitos dos fármacos , Antioxidantes/farmacologia , Suplementos Nutricionais , Ginkgo biloba , Extratos Vegetais/farmacologia , Animais , Antioxidantes/administração & dosagem , Caenorhabditis elegans/efeitos dos fármacos , Alimento Funcional , Fitoterapia , Extratos Vegetais/administração & dosagem , Sementes
20.
Genes (Basel) ; 12(11)2021 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-34828297

RESUMO

Aging is one of the hottest topics in biomedicine. Previous research suggested that ω-3 fatty acids have preventive effects on aging. However, most of previous studies on the anti-aging effects of ω-3 fatty acids are focused on clinical observations, and the anti-aging mechanisms of ω-3 fatty acids have not been fully elucidated. This stimulated our interest to use multi-omics data related to ω-3 fatty acids in order to interpret the anti-aging mechanisms of ω-3 fatty acids. First, we found that ω-3 fatty acids can affect methylation levels and expression levels of genes associated with age-related diseases or pathways in humans. Then, a Mendelian randomization analysis was conducted to determine whether there is a causal relationship between the effect of ω-3 fatty acids on blood lipid levels and variation in the gut microbiome. Our results indicate that the impact of ω-3 fatty acids on aging is partially mediated by the gut microbiome (including Actinobacteria, Bifidobacteria and Streptococcus). In conclusion, this study provides deeper insights into the anti-aging mechanisms of ω-3 fatty acids and supports the dietary supplementation of ω-3 fatty acids in aging prevention.


Assuntos
Envelhecimento/efeitos dos fármacos , Envelhecimento/genética , Ácidos Graxos Ômega-3/farmacologia , Adulto , Envelhecimento/sangue , Animais , Metilação de DNA/efeitos dos fármacos , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Óleos de Peixe/administração & dosagem , Óleos de Peixe/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/genética , Perfilação da Expressão Gênica , Genômica/métodos , Gerociência , Humanos , Recém-Nascido , Análise da Randomização Mendeliana , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto Jovem
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