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1.
Nature ; 574(7779): 553-558, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31645721

RESUMO

Age-associated chronic inflammation (inflammageing) is a central hallmark of ageing1, but its influence on specific cells remains largely unknown. Fibroblasts are present in most tissues and contribute to wound healing2,3. They are also the most widely used cell type for reprogramming to induced pluripotent stem (iPS) cells, a process that has implications for regenerative medicine and rejuvenation strategies4. Here we show that fibroblast cultures from old mice secrete inflammatory cytokines and exhibit increased variability in the efficiency of iPS cell reprogramming between mice. Variability between individuals is emerging as a feature of old age5-8, but the underlying mechanisms remain unknown. To identify drivers of this variability, we performed multi-omics profiling of fibroblast cultures from young and old mice that have different reprogramming efficiencies. This approach revealed that fibroblast cultures from old mice contain 'activated fibroblasts' that secrete inflammatory cytokines, and that the proportion of activated fibroblasts in a culture correlates with the reprogramming efficiency of that culture. Experiments in which conditioned medium was swapped between cultures showed that extrinsic factors secreted by activated fibroblasts underlie part of the variability between mice in reprogramming efficiency, and we have identified inflammatory cytokines, including TNF, as key contributors. Notably, old mice also exhibited variability in wound healing rate in vivo. Single-cell RNA-sequencing analysis identified distinct subpopulations of fibroblasts with different cytokine expression and signalling in the wounds of old mice with slow versus fast healing rates. Hence, a shift in fibroblast composition, and the ratio of inflammatory cytokines that they secrete, may drive the variability between mice in reprogramming in vitro and influence wound healing rate in vivo. This variability may reflect distinct stochastic ageing trajectories between individuals, and could help in developing personalized strategies to improve iPS cell generation and wound healing in elderly individuals.


Assuntos
Envelhecimento/metabolismo , Reprogramação Celular , Senescência Celular/fisiologia , Fibroblastos/metabolismo , Cicatrização , Animais , Linhagem Celular , Reprogramação Celular/efeitos dos fármacos , Meios de Cultivo Condicionados/farmacologia , Citocinas/metabolismo , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Células-Tronco Pluripotentes Induzidas/metabolismo , Mediadores da Inflamação/metabolismo , Judeus/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Análise de Sequência de RNA , Transdução de Sinais/efeitos dos fármacos , Análise de Célula Única , Processos Estocásticos , Fatores de Tempo , Cicatrização/efeitos dos fármacos
2.
Adv Gerontol ; 32(3): 364-369, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31512422

RESUMO

Among the diseases of the cardiovascular system in elderly people, ischemic heart disease and myocardial infarction (MI) occupy the first place in the structure of mortality. One of the main causes of disability and death from MI is late diagnosis. In this regard, the search for new, highly informative and non-invasive methods for diagnosing MI is an important task of molecular gerontology. An enzyme immunoassay showed that the concentration of TNF-α, IL-8 cytokines and p16 aging marker in saliva in elderly people without cardiovascular pathologies (CP) increases in 2,1-4,8 times as compared with middle-aged people. At the same time, in elderly people without CP the concentration in the saliva of the hormone irisin (FNDC5) decreases by 1,8 times as compared with middle-aged people. In middle-aged patients with MI the concentration of IL-8, TNF-α, MMP8, MMP9 in saliva increases 4,3-15,3 times, and FNDC5 decreases 1,8 times compared with those parameters without CP in this age group. In elderly people with MI the concentration of IL-8, TNF-α, MMP8 and MMP9 in saliva increases 4,3-7,1 times as compared with elderly people without CP. Thus, the study of the concentration of signaling molecules IL-8, TNF-α, MMP8, MMP9 in saliva can be used as a non-invasive method for diagnosing MI in people of middle and elderly age. To assess the rate of aging of the organism in middle-aged and elderly people without CP, a study of the concentration of p16 and FNDC5 molecules in saliva is recommended.


Assuntos
Envelhecimento , Infarto do Miocárdio , Saliva , Idoso , Envelhecimento/metabolismo , Biomarcadores/metabolismo , Citocinas/metabolismo , Humanos , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Saliva/química , Fator de Necrose Tumoral alfa/metabolismo
3.
Nat Med ; 25(9): 1385-1389, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31501613

RESUMO

The worldwide obesity epidemic1 makes it important to understand how lipid turnover (the capacity to store and remove lipids) regulates adipose tissue mass. Cross-sectional studies have shown that excess body fat is associated with decreased adipose lipid removal rates2,3. Whether lipid turnover is constant over the life span or changes during long-term weight increase or loss is unknown. We determined the turnover of fat cell lipids in adults followed for up to 16 years, by measuring the incorporation of nuclear bomb test-derived 14C in adipose tissue triglycerides. Lipid removal rate decreases during aging, with a failure to reciprocally adjust the rate of lipid uptake resulting in weight gain. Substantial weight loss is not driven by changes in lipid removal but by the rate of lipid uptake in adipose tissue. Furthermore, individuals with a low baseline lipid removal rate are more likely to remain weight-stable after weight loss. Therefore, lipid turnover adaptation might be important for maintaining pronounced weight loss. Together these findings identify adipose lipid turnover as an important factor for the long-term development of overweight/obesity and weight loss maintenance in humans.


Assuntos
Envelhecimento/metabolismo , Peso Corporal/genética , Obesidade/metabolismo , Ganho de Peso/genética , Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Adolescente , Adulto , Envelhecimento/genética , Envelhecimento/patologia , Peso Corporal/fisiologia , Radioisótopos de Carbono/química , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Metabolismo dos Lipídeos/genética , Lipídeos/genética , Masculino , Obesidade/genética , Obesidade/patologia , Sobrepeso/genética , Sobrepeso/metabolismo , Sobrepeso/patologia , Triglicerídeos/metabolismo , Perda de Peso/genética
4.
J Agric Food Chem ; 67(37): 10342-10351, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31461273

RESUMO

Maltol, a maillard reaction product from ginseng (Panax ginseng C. A. Meyer), has been confirmed to inhibit oxidative stress in several animal models. Its beneficial effect on oxidative stress related brain aging is still unclear. In this study, the mouse model of d-galactose (d-Gal)-induced brain aging was employed to investigate the therapeutic effects and potential mechanisms of maltol. Maltol treatment significantly restored memory impairment in mice as determined by the Morris water maze tests. Long-term d-Gal treatment reduced expression of cholinergic regulators, i.e., the cholineacetyltransferase (ChAT) (0.456 ± 0.10 vs 0.211 ± 0.03 U/mg prot), the acetylcholinesterase (AChE) (36.4 ± 5.21 vs 66.5 ± 9.96 U/g). Maltol treatment prevented the reduction of ChAT and AChE in the hippocampus. Maltol decreased oxidative stress levels by reducing levels of reactive oxygen species (ROS) and malondialdehyde (MDA) production in the brain and by elevating antioxidative enzymes. Furthermore, maltol treatment minimized oxidative stress by increasing the phosphorylation levels of phosphatidylinositol-3-kinase (PI3K), protein kinase B (Akt), nuclear factor-erythroid 2-related factor 2 (Nrf2), and hemeoxygenase-1 (HO-1). The above results clearly indicate that supplementation of maltol diminishes d-Gal-induced behavioral dysfunction and neurological deficits via activation of the PI3K/Akt-mediated Nrf2/HO-1 signaling pathway in brain. Maltol might become a potential drug to slow the brain aging process and stimulate endogenous antioxidant defense capacity. This study provides the novel evidence that maltol may slow age-associated brain aging.


Assuntos
Envelhecimento/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Galactose/efeitos adversos , Heme Oxigenase-1/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Extratos Vegetais/administração & dosagem , Pironas/administração & dosagem , Envelhecimento/metabolismo , Animais , Heme Oxigenase-1/genética , Humanos , Masculino , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Fator 2 Relacionado a NF-E2/genética , Estresse Oxidativo/efeitos dos fármacos , Panax/química , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo
5.
Br J Anaesth ; 123(3): 288-297, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31279479

RESUMO

BACKGROUND: Minimum alveolar concentration (MAC) and MAC-awake decrease with age. We hypothesised that, in clinical practice, (i) end-tidal MAC fraction in older patients would decline by less than the predicted age-dependent MAC decrease (i.e. older patients would receive relatively excessive anaesthetic concentrations), and (ii) bispectral index (BIS) values would therefore be lower in older patients. METHODS: We examined the relationship between end-tidal MAC fraction, BIS values, and age in 4699 patients > 30 yr in age at a single centre using unadjusted local regression (locally estimated scatterplot smoothing), Spearman's correlation, stratification, and robust univariable and multivariable linear regression. RESULTS: The end-tidal MAC fraction in older patients declined by 3.01% per decade (95% confidence interval [CI]: 2.56-3.45; P<0.001), less than the 6.47% MAC decrease per decade that we found in a meta-regression analysis of published studies of age-dependent changes in MAC (P<0.001), and less than the age-dependent decrease in MAC-awake. The BIS values correlated positively with age (ρ=0.15; 95% CI: 0.12-0.17; P<0.001), and inversely with the age-adjusted end-tidal MAC (aaMAC) fraction (ρ= -0.13; 95% CI: -0.16, -0.11; P<0.001). CONCLUSIONS: The age-dependent decline in end-tidal MAC fraction delivered in clinical practice at our institution was less than the age-dependent percentage decrease in MAC and MAC-awake determined from published studies. Despite receiving higher aaMAC fractions, older patients paradoxically showed higher BIS values. This most likely suggests that the BIS algorithm is inaccurate in older adults.


Assuntos
Envelhecimento/fisiologia , Anestésicos Inalatórios/farmacologia , Eletroencefalografia/efeitos dos fármacos , Adulto , Fatores Etários , Idoso , Envelhecimento/metabolismo , Anestésicos Inalatórios/administração & dosagem , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória/métodos , Alvéolos Pulmonares/metabolismo , Estudos Retrospectivos
6.
High Blood Press Cardiovasc Prev ; 26(4): 321-329, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31325087

RESUMO

Cardiovascular disease (CVD) remains the leading cause of morbility and mortality worldwide. The identification of common cardiovascular risk factors has led to the development of effective treatments that enabled a significant reduction of the global cardiovascular disease burden. However, a significant proportion of cardiovascular risk remains unexplained by these risk factors leaving many individuals at risk of cardiovascular events despite good control of the risk factors. Recent randomized clinical trials and Mendelian randomization studies have suggested that inflammation explains a significant proportion of the residual cardiovascular risk in subjects with good control of risk factors. An accelerated process of vascular ageing is increasingly recognized as a potential mechanism by which inflammation might increase the risk of CVD. In turn, cellular ageing represents an important source of inflammation within the vascular wall, potentially creating a vicious cycle that might promote progression of atherosclerosis, independently from the individual cardiovascular risk factor burden. In this review, we summarise current evidence suggesting a role for biological ageing in CVD and how inflammation might act as a key mediator of this association.


Assuntos
Envelhecimento/metabolismo , Doenças Cardiovasculares/metabolismo , Mediadores da Inflamação/metabolismo , Inflamação/metabolismo , Telômero/metabolismo , Fatores Etários , Envelhecimento/genética , Envelhecimento/patologia , Animais , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/patologia , Doenças Cardiovasculares/fisiopatologia , Senescência Celular , Humanos , Inflamação/genética , Inflamação/patologia , Inflamação/fisiopatologia , Medição de Risco , Fatores de Risco , Transdução de Sinais , Telômero/genética , Telômero/patologia , Homeostase do Telômero , Encurtamento do Telômero , Fatores de Tempo
7.
J Microbiol ; 57(9): 812-820, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31201723

RESUMO

Sanghuangporus sanghuang is a well-known pharmacodynamic and economically important edible fungus associated with mulberry (Morus spp.). A distinctly new exopolysaccharide (EPS), designated SHP-2 was obtained from S. sanghuang P0988 broth, and its structure and anti-aging prosperity were characterized. SHP-2 was found to be composed of a back-bone of →4)-ß-Manp-(1→4)-α-Araf-(1→3,4)-α-Glcp(1→3,4)-α-Glcp-(1→3,4)-α-Glcp-(1→3,4)-α-Glcp-(1→3,4)-α-Glcp-(1→6)-α-Galp-(1→4)-ß-Manp-(1→ and five branches, including four α-D-Glcp-(1→ and one α-D-Manp-(1→SHP-2 was shown to increase antioxidant enzyme activities including catalase (CAT) and superoxide dismutase (SOD) activities, as well as trolox equivalent antioxidant (TEAC) capacity in serum of mice pre-treated with D-Gal, while reducing lipofuscin levels. SHP-2 exerted a favorable influence on immune organ coefficients and ameliorated the histopathological hepatic lesions and apoptosis in hepatocytes of D-galactose-aged mice almost in a dose-dependent manner. Using the same analytical methods, on comparison with previously studied EPS compounds (i.e. SHP-1), SHP-2 was found to have more complex structure, larger molecule weight, and different anti-aging properties. The results presented here suggest that not only does EPS bioactivity vary with respect to molecular structures and molecule weight, but that multiple structures with different activity can be expressed by a single fungal strain. These results may help understanding the anti-aging prosperity of these polysaccharides for use in health foods or dietary supplements.


Assuntos
Basidiomycota/química , Polissacarídeos/química , Polissacarídeos/farmacologia , Envelhecimento/efeitos dos fármacos , Envelhecimento/metabolismo , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Sequência de Carboidratos , Catalase/metabolismo , Feminino , Hepatócitos/citologia , Hepatócitos/efeitos dos fármacos , Lipofuscina/metabolismo , Espectroscopia de Ressonância Magnética , Masculino , Camundongos , Peso Molecular , Capacidade de Absorbância de Radicais de Oxigênio , Superóxido Dismutase/metabolismo
8.
Environ Pollut ; 246: 904-913, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31159140

RESUMO

Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) has been frequently detected in environmental media and biological samples. However, knowledge of its adverse health consequences is limited. In the current study, Caenorhabditis elegans (C. elegans, L1 larvae) were exposed to TDCPP at environmentally relevant concentrations (control, 0.1, 1, 100 and 1000 µg L-1) for 72 h to explore any association between TDCPP and the aging process. Some of the degenerative age-related indicators were observed, including locomotion behaviors and lifespan. As crucial biomarkers of aging, the accumulation of lipofuscin, and lipid peroxidation (LPO) products exemplified by 4-hydroxynon-2-enal (4-HNE) were detected. This product forms as a result of oxidative stress, as confirmed by an N-acetyl-L-cysteine (NAC) pharmacological assay. Moreover, a significant increase in reactive oxide species (ROS) production in a dose-dependent manner using a fluorescent probe was observed. For the underlying molecular mechanism of the above aging phenotypes, significantly upregulated transcription of genes related to antioxidant systems, especially a subset of glutathione S-transferase (gst-5, gst-6, gst-9, gst-10, gst-19, gst-24, gst-26, gst-29, gst-33, and gst-38), was found by RNA-Seq and further confirmed by RT-qPCR. The elevated glutathione S-transferase (GST) was attributed to the significant increase in 4-HNE because mutations in gst-5 and gst-24 inhibited the conjugation of GSTs with 4-HNE. Therefore, GST play an indispensable role in the detoxification process of TDCPP exposure and further confirmed LPO accumulation at the molecular mechanism level. In conclusion, TDCPP accelerated the aging process induced by the LPO products, 4-HNE, response to reactive oxidative species in C. elegans.


Assuntos
Envelhecimento/efeitos dos fármacos , Aldeídos/metabolismo , Poluentes Ambientais/toxicidade , Compostos Organofosforados/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Envelhecimento/genética , Envelhecimento/metabolismo , Animais , Caenorhabditis elegans/fisiologia , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Peroxidação de Lipídeos , Estresse Oxidativo
9.
Aging Clin Exp Res ; 31(6): 793-798, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31148100

RESUMO

Risk for or established malnutrition is frequent in older adults, accompanied by functional limitations, increased morbidity and mortality. Protein-energy malnutrition is often observed and leads besides other predisposing factors to sarcopenia, the increased loss of muscle mass with aging. Sarcopenia is an integral correlate of the physical component of the frailty syndrome. Even though sarcopenia often reaches levels where mobility, balance and functionality on overall are hampered, its diagnosis has not become part of the standard diagnostic and therapeutic repertoire of geriatric medicine. This will hopefully change with a recently published revised international definition of sarcopenia, as well an own ICD-number. From a pathophysiological point of view, both malnutrition and sarcopenia share many components, a low-inflammatory state (inflamm-aging) being an important one. Nutritional interventions with and without parallel physical activity programs can prevent and often also reverse sarcopenia. It is hoped that upcoming even more potent nutritional treatment options-including for sarcopenic obesity-will lower the burden of malnutrition and sarcopenia for many older adults.


Assuntos
Fragilidade/etiologia , Desnutrição/complicações , Sarcopenia/etiologia , Idoso , Envelhecimento/metabolismo , Exercício/fisiologia , Idoso Fragilizado , Fragilidade/fisiopatologia , Fragilidade/prevenção & controle , Humanos , Sarcopenia/fisiopatologia , Sarcopenia/prevenção & controle
10.
Int J Mol Sci ; 20(11)2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31174250

RESUMO

Aging is a physiologic/pathologic process characterized by a progressive impairment of cellular functions, supported by the alterations of several molecular pathways, leading to an increased cell susceptibility to injury. This deterioration is the primary risk factor for several major human pathologies. Numerous cellular processes, including genomic instability, telomere erosion, epigenetic alterations, loss of proteostasis, deregulated nutrient-sensing, mitochondrial dysfunction, stem cell exhaustion, and altered intercellular signal transduction represent common denominators of aging in different organisms. Mammalian target of rapamycin (mTOR) is an evolutionarily conserved nutrient sensing protein kinase that regulates growth and metabolism in all eukaryotic cells. Studies in flies, worms, yeast, and mice support the hypothesis that the mTOR signalling network plays a pivotal role in modulating aging. mTOR is emerging as the most robust mediator of the protective effects of various forms of dietary restriction, which has been shown to extend lifespan and slow the onset of age-related diseases across species. Herein we discuss the role of mTor signalling network in the development of classic age-related diseases, focused on cardiovascular system, immune response, and cancer.


Assuntos
Envelhecimento/metabolismo , Doenças Cardiovasculares/etiologia , Doenças do Sistema Imunitário/etiologia , Neoplasias/etiologia , Serina-Treonina Quinases TOR/metabolismo , Envelhecimento/genética , Animais , Evolução Molecular , Humanos , Transdução de Sinais , Serina-Treonina Quinases TOR/genética
11.
Oxid Med Cell Longev ; 2019: 2867516, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31049131

RESUMO

Reactive Oxygen Species (ROS) play an essential dual role in living systems. Healthy levels of ROS modulate several signaling pathways, but at the same time, when they exceed normal physiological amounts, they work in the opposite direction, playing pivotal functions in the pathophysiology of multiple severe medical conditions (i.e., cancer, diabetes, neurodegenerative and cardiovascular diseases, and aging). Therefore, the research for methods to detect their levels via light-sensitive fluorescent probes has been extensively studied over the years. However, this is not the only link between light and ROS. In fact, the modulation of ROS mediated by light has been exploited already for a long time. In this review, we report the state of the art, as well as recent developments, in the field of photostimulation of oxidative stress, from photobiomodulation (PBM) mediated by naturally expressed light-sensitive proteins to the most recent optogenetic approaches, and finally, we describe the main methods of exogenous stimulation, in particular highlighting the new insights based on optically driven ROS modulation mediated by polymeric materials.


Assuntos
Antioxidantes/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Diabetes Mellitus/tratamento farmacológico , Doenças Neurodegenerativas/tratamento farmacológico , Espécies Reativas de Oxigênio/antagonistas & inibidores , Envelhecimento/efeitos dos fármacos , Envelhecimento/metabolismo , Envelhecimento/patologia , Animais , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Diabetes Mellitus/metabolismo , Diabetes Mellitus/patologia , Humanos , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/patologia , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
12.
J Sci Food Agric ; 99(12): 5350-5357, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31049985

RESUMO

BACKGROUND: Bee pollen has been regarded as a complete nutritional human dietary supplement but its nutrient absorption and biological effects may be restricted by the complex pollen wall. The aim of this study was to explore the effects of ultrasonic and ball-milling treatment on the release of nutritional components and on in vitro and in vivo antioxidant effects of rose (Rosa rugosa) bee pollen. RESULTS: Bee pollen walls were broken to varying degrees, nutrients were released, and in vitro and in vivo antioxidant effects of bee pollen were improved. The scavenging effects of 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azinobis(3-ethylbenzothiazolone-6-sulfonic acid) (ABTS) radicals, and oxygen radical absorbance capacity (ORAC) were improved. In aging mice, wall-breaking treatment led to better organ recovery, enhanced superoxide dismutase (SOD) and catalase (CAT) effects, and malondialdehyde (MDA) reduction. Eight compounds of rose bee pollen ethanol extract, including isorhamnetin 3-O-diglucoside and N', N″, N‴-dicaffeoyl p-coumaroyl spermidine were identified by ultra-performance liquid chromatography electrospray ionization quadrupole time of flight mass spectrometry (UPLC-ESI-QTOF-MS/MS) assay. CONCLUSION: This study showed that ultrasonic treatment had greater wall-disruption effects of bee pollen on nutrient release and antioxidant effect promotion. In conclusion, rose bee pollen, with wall-breaking treatments, may have potential value as an ingredient in functional food processing. © 2019 Society of Chemical Industry.


Assuntos
Antioxidantes/química , Parede Celular/química , Manipulação de Alimentos/métodos , Extratos Vegetais/química , Pólen/química , Rosa/química , Ultrassom/métodos , Envelhecimento/metabolismo , Animais , Antioxidantes/isolamento & purificação , Antioxidantes/metabolismo , Manipulação de Alimentos/instrumentação , Alimento Funcional/análise , Malondialdeído/metabolismo , Camundongos , Nutrientes/isolamento & purificação , Nutrientes/metabolismo , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/metabolismo , Pólen/metabolismo , Rosa/metabolismo , Superóxido Dismutase/metabolismo
13.
J Med Food ; 22(5): 469-478, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31084539

RESUMO

Aging and lifestyle factors, including high-sugar and high-fat diets, promote a systemic metabolic imbalance that promotes neurodegeneration. Hericium erinaceus has long been used in traditional Chinese medicine. Recently, its functional activities, such as antimetabolic dysfunction, antineuroinflammatory activities, and stimulation of nerve growth factor (NGF) synthesis, have been revealed. This study demonstrated that Hericium erinaceus mycelium (HEM) and an isolated diterpenoid derivative, erinacine A (EA), may reverse spatial learning disabilities in aging mice (15 months old) fed with a high-fat and high-sucrose diet (HFSD). Aging mice were randomly assigned to one of four treatment groups: (1) a chow diet (control), (2) an HFSD, and an HFSD supplemented with either (3) HEM or (4) EA for 18 weeks. The Morris water maze (MWM) and Y-maze were used for behavioral assessments. Both HEM- and EA-treated mice had shorter mean daily escape latencies than HFSD-treated mice in the MWM. In addition, HEM-treated mice had a slightly increased exploratory time and frequency in the novel arm in the Y-maze. Quantitative PCR revealed that both HEM- and EA-treated mice exhibited reduced messenger RNA (mRNA) expression of tumor necrosis factor-α, interleukin-1ß, and HEM-treated mice exhibited increased mRNA expression of NGF and NeuN in the hippocampus. Moreover, HEM and EA also decreased body weight, abdominal fat, plasma glucose, serum and liver total cholesterol, and liver triacylglycerol. Thus, HEM may be a potential health-promoting supplement for minimizing the progression of aging and obesity-induced neurodegeneration by reducing metabolic abnormalities and neuroinflammatory cytokines and increasing neurogenesis factors.


Assuntos
Envelhecimento/efeitos dos fármacos , Basidiomycota/química , Dieta Hiperlipídica/efeitos adversos , Diterpenos/administração & dosagem , Doenças Metabólicas/tratamento farmacológico , Sacarose/efeitos adversos , Envelhecimento/metabolismo , Envelhecimento/psicologia , Animais , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Humanos , Masculino , Aprendizagem em Labirinto , Doenças Metabólicas/etiologia , Doenças Metabólicas/metabolismo , Doenças Metabólicas/psicologia , Camundongos , Camundongos Endogâmicos C57BL , Micélio/química , Fator de Crescimento Neural/genética , Fator de Crescimento Neural/metabolismo , Aprendizagem Espacial/efeitos dos fármacos
14.
Food Funct ; 10(5): 2774-2784, 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31049500

RESUMO

The aging process is usually associated with increased oxidative stress and deficiency of tissues and organs, which causes a decline in the life quality of individuals. Some anti-oxidant factors derived from foods have been implicated in delaying senescence and sustaining health. The present study aimed to assess the anti-aging effects and underlying mechanism of the combined application of chicken embryo (CE) extract and a nutritional mixture (NM) of 52 ingredients on the aging process of d-galactose (d-gal)-induced rats. After 90 days of treatment, we observed that CE plus NM administration significantly improved the body weight, visceral indices and histological damage of aging rats. The use of CE or NM alone exhibited similar effects, but was not as effective as the combined use of CE and NM. In addition, the additional nutrients promoted the mitochondrial function of d-galactose-induced rats. With CE + NM supplementation, cells from senescent rats showed decreased accumulation of reactive oxygen species (ROS), increased levels of mitochondrial membrane potential, elevated numbers of mitochondria, and morphological changes towards normalization compared to the un-treated group. Furthermore, autophagosomes and autophagy-related proteins were up-regulated in aging rats upon exposure to CE + NM. Interestingly, we also found that the protein extracts of CE have similar effects to CE. These results indicate the critical role played by CE + NM in promoting the function of mitochondria and autophagy, therefore regulating the aging process in rats. Our study provides a novel compound design of nutritional support to achieve an optimal nutritional status for anti-oxidation and slowing of aging.


Assuntos
Envelhecimento/metabolismo , Autofagia , Embrião de Galinha/química , Ovos/análise , Galactose/efeitos adversos , Mitocôndrias/metabolismo , Animais , Suplementos Nutricionais/análise , Feminino , Galactose/metabolismo , Humanos , Masculino , Potencial da Membrana Mitocondrial , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo
15.
Anticancer Res ; 39(5): 2447-2451, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31092438

RESUMO

BACKGROUND/AIM: The insulin-like growth factor 1 (IGF1) signaling pathway as an aging mechanism related to p53 in human melanogenesis remains unclear. The aim of this study was to investigate the relationship between p53 and IGF1 signaling pathway in young, senescent and H2O2-treated cells. MATERIALS AND METHODS: The protein and gene expression in young, senescent and H2O2-treated cells were analyzed using western blot and reverse transcription polymerase chain reaction (RT-PCR) assays, respectively. RESULTS: The expression levels of (phosphoinositide 3-kinases) PI3K, v-akt murine thymoma viral oncogene homolog 1 (AKT1), mammalian target of rapamycin, ß-catenin (CTNNB1), acetylated p53 (ac-p53), p53 and p-p21 proteins, related to IGF1 and p53 signaling pathways, were higher in senescent and H2O2-treated cells than those of young cells. Furthermore, AKT reduced melanogenesis through microphthalmia-associated transcription factor (MITF) inactivation by the inhibition of CTNNB1. The gene expression levels of PI3K, TP53 and catalase (CAT) in senescent and H2O2-treated cells were increased compared to young cells. CONCLUSION: p53 protein plays a key role in the aging of melanocytes via IGF1 signaling pathways.


Assuntos
Envelhecimento/genética , Proliferação de Células/genética , Fator de Crescimento Insulin-Like I/genética , Proteína Supressora de Tumor p53/genética , Envelhecimento/metabolismo , Envelhecimento/patologia , Animais , Catalase/genética , Proliferação de Células/efeitos dos fármacos , Senescência Celular/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Peróxido de Hidrogênio/toxicidade , Melanócitos/metabolismo , Melanócitos/patologia , Camundongos , Fator de Transcrição Associado à Microftalmia/genética , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais/efeitos dos fármacos , beta Catenina/antagonistas & inibidores , beta Catenina/genética
16.
Mol Cell Biochem ; 459(1-2): 73-82, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31104265

RESUMO

Currently we face the issues of aging-associated pathologies, particularly those leading to heart failure. With that in mind, in current research we focus on aging and hypertension combination as a widely spread threating problem. In a row with functional and morphological characterization of these aging- and hypertension-associated cardiac changes, we evaluate biogenesis of microRNA-1 being one of major microRNAs in the heart. The aim of this study was to check the hypothesis if dysregulation of microRNA-1 biogenesis is associated with heart failure in aged and especially aged hypertensive rats. The experiments were carried out on male SHR and Wistar rats of age 6 months (young) and 18 months (old). The evaluation of hemodynamic parameters was performed in heart left ventricles of narcotized rats using the ultra-small 2F catheter. The development of fibrosis was determined using light and electron microscopy. Levels of mature and immature forms of microRNA-1 and mRNA encoding the proteins involved in its biogenesis were determined using reverse transcription and quantitative PCR. Aging of both Wistar and SHRs is accompanied with altered hemodynamic parameters compared with correspondent younger mates. SHRs, especially old ones, demonstrated significant heart fibrosis. In aged animals, the level of primary microRNA-1 in Wistar rats were 7 times higher (p < 0.05) and in SHR 17 times higher (p < 0.05) in comparison with young rats of the same strain. We also observed 22 times higher level of immature microRNA-1 in the heart of Wistar and 5.9 times higher level for aged hypertensive rats (p < 0.05) compared to young rats. At the same time, the level of mature microRNA-1 occurred 2.5 and 3.2 times lower in respective groups (p < 0.05). In the current study, we observe the significant dysregulation of microRNA-1 processing in the heart associated with aging and arterial hypertension.


Assuntos
Envelhecimento/metabolismo , Insuficiência Cardíaca/metabolismo , Hipertensão/metabolismo , MicroRNAs/biossíntese , Miocárdio/metabolismo , Envelhecimento/patologia , Animais , Fibrose , Insuficiência Cardíaca/patologia , Hipertensão/patologia , Masculino , Miocárdio/patologia , Ratos , Ratos Endogâmicos SHR , Ratos Wistar
17.
Biomed Res Int ; 2019: 8748253, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31080832

RESUMO

Aging is related to a number of functional and morphological changes leading to progressive decline of the biological functions of an organism. Reactive Oxygen Species (ROS), released by several endogenous and exogenous processes, may cause important oxidative damage to DNA, proteins, and lipids, leading to important cellular dysfunctions. The imbalance between ROS production and antioxidant defenses brings to oxidative stress conditions and, related to accumulation of ROS, aging-associated diseases. The purpose of this review is to provide an overview of the most relevant data reported in literature on the natural compounds, mainly phytochemicals, with antioxidant activity and their potential protective effects on age-related diseases such as metabolic syndrome, diabetes, cardiovascular disease, cancer, neurodegenerative disease, and chronic inflammation, and possibly lower side effects, when compared to other drugs.


Assuntos
Envelhecimento/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Envelhecimento/metabolismo , Animais , Antioxidantes/metabolismo , Antioxidantes/uso terapêutico , Humanos , Síndrome Metabólica/tratamento farmacológico , Síndrome Metabólica/metabolismo , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/metabolismo , Espécies Reativas de Oxigênio/metabolismo
18.
Int J Mol Sci ; 20(10)2019 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-31137890

RESUMO

While mitochondrial dysfunction is acknowledged as a major feature of aging, much less is known about the role of mitochondria in extended longevity. Livers from aged (28-month-old) and extremely aged (32-month-old) rats were analyzed for citrate synthase activity, mitochondrial transcription factor A (TFAM) amount, mitochondrial DNA (mtDNA), and 4.8 Kb "common deletion" contents. None of the assayed parameters differed significantly between age groups. TFAM-binding to mtDNA and the incidence of 8-oxo-deoxyguanosine in specific mtDNA regions, encompassing the origins of mtDNA replication (D-loop and Ori-L) and the 16-bp long direct repeat 1 (DR1) of the 4.8 Kb deletion, were determined. A decrease in TFAM binding was unveiled at all regions in extremely aged in comparison with aged rats. Reduced incidence of oxidized purines at all assayed regions was detected in 32-month-old rats compared with the 28-month-old group. A significant positive correlation between the incidence of 8-oxo-deoxoguanosine and TFAM-bound mtDNA was found at D-Loop and Ori-L regions only in 28-month-old rats. The absence of such correlation in 32-month-old rats indicates a different, fine-tuned regulation of TFAM binding in the two age groups and supports the existence of two different paces in aging and extended aging.


Assuntos
Envelhecimento/metabolismo , Dano ao DNA , Mitocôndrias Hepáticas/metabolismo , Fatores de Transcrição/metabolismo , Envelhecimento/genética , Animais , DNA Mitocondrial/metabolismo , Fígado/crescimento & desenvolvimento , Fígado/metabolismo , Masculino , Ligação Proteica , Ratos
19.
Nat Med ; 25(6): 988-1000, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31086348

RESUMO

An aged circulatory environment can activate microglia, reduce neural precursor cell activity and impair cognition in mice. We hypothesized that brain endothelial cells (BECs) mediate at least some of these effects. We observe that BECs in the aged mouse hippocampus express an inflammatory transcriptional profile with focal upregulation of vascular cell adhesion molecule 1 (VCAM1), a protein that facilitates vascular-immune cell interactions. Concomitantly, levels of the shed, soluble form of VCAM1 are prominently increased in the plasma of aged humans and mice, and their plasma is sufficient to increase VCAM1 expression in cultured BECs and the hippocampi of young mice. Systemic administration of anti-VCAM1 antibody or genetic ablation of Vcam1 in BECs counteracts the detrimental effects of plasma from aged individuals on young brains and reverses aging aspects, including microglial reactivity and cognitive deficits, in the brains of aged mice. Together, these findings establish brain endothelial VCAM1 at the blood-brain barrier as a possible target to treat age-related neurodegeneration.


Assuntos
Envelhecimento/sangue , Encéfalo/metabolismo , Células-Tronco Neurais/metabolismo , Molécula 1 de Adesão de Célula Vascular/metabolismo , Adolescente , Adulto , Idoso , Envelhecimento/imunologia , Envelhecimento/metabolismo , Animais , Barreira Hematoencefálica/imunologia , Barreira Hematoencefálica/metabolismo , Encéfalo/citologia , Células Cultivadas , Células Endoteliais/metabolismo , Feminino , Deleção de Genes , Hipocampo/citologia , Hipocampo/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos Knockout , Camundongos SCID , Microglia/metabolismo , Células-Tronco Neurais/citologia , Molécula 1 de Adesão de Célula Vascular/sangue , Molécula 1 de Adesão de Célula Vascular/genética , Adulto Jovem
20.
Nat Commun ; 10(1): 2191, 2019 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-31113955

RESUMO

The long-lived proteome constitutes a pool of exceptionally stable proteins with limited turnover. Previous studies on ubiquitin-mediated protein degradation primarily focused on relatively short-lived proteins; how ubiquitylation modifies the long-lived proteome and its regulatory effect on adult lifespan is unclear. Here we profile the age-dependent dynamics of long-lived proteomes in Drosophila by mass spectrometry using stable isotope switching coupled with antibody-enriched ubiquitylome analysis. Our data describe landscapes of long-lived proteins in somatic and reproductive tissues of Drosophila during adult lifespan, and reveal a preferential ubiquitylation of older long-lived proteins. We identify an age-modulated increase of ubiquitylation on long-lived histone 2A protein in Drosophila, which is evolutionarily conserved in mouse, monkey, and human. A reduction of ubiquitylated histone 2A in mutant flies is associated with longevity and healthy lifespan. Together, our data reveal an evolutionarily conserved biomarker of aging that links epigenetic modulation of the long-lived histone protein to lifespan.


Assuntos
Envelhecimento/metabolismo , Histonas/metabolismo , Ubiquitinação/fisiologia , Animais , Animais Geneticamente Modificados , Biomarcadores/metabolismo , Encéfalo/metabolismo , Encéfalo/patologia , Drosophila melanogaster , Feminino , Humanos , Longevidade/fisiologia , Macaca mulatta , Masculino , Camundongos , Proteômica/métodos
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