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1.
Nutrients ; 13(6)2021 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-34205338

RESUMO

This study investigated the antioxidant effects of whey protein peptide on learning and memory in aging C57BL/6N mice. A total of 72 SPF male C57BL/6N mice were used. Twelve mice were randomly selected as the control group, and the other mice were intraperitoneally injected with D-galactose (100 mg/kg body weight for 6 weeks), during which, the mice in the control group were intraperitoneally injected with the same amount of normal saline. After 6 weeks, the blood was taken from the epicanthus and the serum MDA level was measured, according to which, the mice were randomly divided into the model control group, the whey protein group (1.5 g/kg body weight), and three Whey protein peptide (WHP) intervention groups (0.3 g/kg body weight, 1.5 g/kg body weight, 3.0 g/kg body weight). The water solution of the test sample was administered by oral gavage every day. The intervention period was 30 days, during which, the model control group, the whey protein group, and the whey protein peptide group continued receiving intraperitoneal injections of D-galactose, while the control group continued receiving intraperitoneal injections of normal saline. After the intervention, behavioral experiments were conducted in the following order: open field test, water maze test, and new object recognition test. After the behavioral experiment, the morphology of hippocampal formation was observed by HE staining and TUNEL labeling. Oxidative stress-related indexes in the serum, liver, and brain were detected. Expression levels of the cholinergic system-related enzymes and proinflammatory cytokines in brain tissue were detected. Western blot was used to detect the expression of synaptic plasticity-related proteins in the mouse brain. The results showed that WHP could significantly improve the accumulation of MDA and PC, increase the activities of SOD and GSH-Px, resist oxidative stress injury, and enhance the potential of endogenous antioxidant defense mechanisms. WHP can significantly improve the decline of aging-related spatial exploration, body movement, and spatial and non-spatial learning/memory ability. Its specific mechanism may be related to reducing the degeneration of hippocampal nerve cells, reducing the apoptosis of nerve cells, improving the activity of AChE, reducing the expression of inflammatory factors (TNF-α and IL-1ß) in brain tissue, reducing oxidative stress injury, and improving the expression of p-CaMKⅡ and BDNF synaptic plasticity protein. These results indicate that WHP can improve aging-related oxidative stress, as well as learning and memory impairment.


Assuntos
Envelhecimento/fisiologia , Antioxidantes/farmacologia , Aprendizagem/efeitos dos fármacos , Memória/efeitos dos fármacos , Peptídeos/administração & dosagem , Proteínas do Soro do Leite/química , Envelhecimento/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/fisiologia , Galactose/administração & dosagem , Hipocampo/citologia , Marcação In Situ das Extremidades Cortadas , Masculino , Malondialdeído/sangue , Camundongos , Camundongos Endogâmicos C57BL , Modelos Animais , Estresse Oxidativo/efeitos dos fármacos
2.
J Clin Neurosci ; 90: 359-362, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34275575

RESUMO

Vagus somatosensory evoked potentials (VSEP) and ultrasonography can be used to detect functional and structural changes of the vagus nerve (VN) that are hypothesized to be associated with neurodegenerative diseases. However, it has not yet been established whether age-related changes in the VN occur in the healthy population. In this pilot study we included healthy volunteers in the 26-30 and 51-55 age range who comprised the younger (n = 20) and older (n = 20) groups, respectively. VSEP were recorded separately for stimulation of the auricular branch of the left and right VN. The VN CSA was measured in the transverse plane proximal to the carotid bifurcation, at the level of the distal end of the common carotid artery. No differences were found between the younger and older groups when comparing the average VN CSA (2.01 ± 0.20 vs 2.05 ± 0.20, mm2; p = 0.570) or the CSA of the right (2.08 ± 0.19 vs 2.17 ± 0.24, mm2; p = 0.233) or left VN (1.94 ± 0.26 vs 1.93 ± 0.24, mm2; p = 0.911). The right VN was larger than the left in 95% (n = 19) of older participants and in 65% (n = 13) of younger participants (p = 0.055). In comparison with the younger group, older participants showed significantly longer VSEP latencies of all wave components for electrodes C4-F4 and Fz-F3, of P1 for electrodes C3-F3 and of N1 and P2 for electrodes Fz-F4. The results of this study indicate that older age is associated with longer VSEP latencies but not with changes in VN CSA.


Assuntos
Envelhecimento/fisiologia , Potenciais Somatossensoriais Evocados/fisiologia , Nervo Vago/diagnóstico por imagem , Nervo Vago/fisiologia , Adulto , Artérias Carótidas/diagnóstico por imagem , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Bainha de Mielina/fisiologia , Ultrassonografia
3.
Nat Commun ; 12(1): 4399, 2021 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-34285221

RESUMO

The decline of neuronal synapses is an established feature of ageing accompanied by the diminishment of neuronal function, and in the motor system at least, a reduction of behavioural capacity. Here, we have investigated Drosophila motor neuron synaptic terminals during ageing. We observed cumulative fragmentation of presynaptic structures accompanied by diminishment of both evoked and miniature neurotransmission occurring in tandem with reduced motor ability. Through discrete manipulation of each neurotransmission modality, we find that miniature but not evoked neurotransmission is required to maintain presynaptic architecture and that increasing miniature events can both preserve synaptic structures and prolong motor ability during ageing. Our results establish that miniature neurotransmission, formerly viewed as an epiphenomenon, is necessary for the long-term stability of synaptic connections.


Assuntos
Envelhecimento/fisiologia , Neurônios Motores/fisiologia , Terminações Pré-Sinápticas/fisiologia , Transmissão Sináptica/fisiologia , Animais , Animais Geneticamente Modificados , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster , Potencial Evocado Motor/fisiologia , Masculino , Microscopia Eletrônica , Modelos Animais , Neurônios Motores/ultraestrutura , Músculos/inervação , Músculos/fisiologia , Músculos/ultraestrutura , Terminações Pré-Sinápticas/ultraestrutura , Fatores de Tempo
4.
Int J Mol Sci ; 22(12)2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34198710

RESUMO

Microglial activity in the aging neuroimmune system is a central player in aging-related dysfunction. Aging alters microglial function via shifts in protein signaling cascades. These shifts can propagate neurodegenerative pathology. Therapeutics require a multifaceted approach to understand and address the stochastic nature of this process. Polyphenols offer one such means of rectifying age-related decline. Our group used mass spectrometry (MS) analysis to explicate the complex nature of these aging microglial pathways. In our first experiment, we compared primary microglia isolated from young and aged rats and identified 197 significantly differentially expressed proteins between these groups. Then, we performed bioinformatic analysis to explore differences in canonical signaling cascades related to microglial homeostasis and function with age. In a second experiment, we investigated changes to these pathways in aged animals after 30-day dietary supplementation with NT-020, which is a blend of polyphenols. We identified 144 differentially expressed proteins between the NT-020 group and the control diet group via MS analysis. Bioinformatic analysis predicted an NT-020 driven reversal in the upregulation of age-related canonical pathways that control inflammation, cellular metabolism, and proteostasis. Our results highlight salient aspects of microglial aging at the level of protein interactions and demonstrate a potential role of polyphenols as therapeutics for age-associated dysfunction.


Assuntos
Envelhecimento/fisiologia , Suplementos Nutricionais , Microglia/metabolismo , Polifenóis/farmacologia , Transdução de Sinais , Animais , Dieta , Ontologia Genética , Masculino , Microglia/efeitos dos fármacos , Proteoma/metabolismo , Ratos Endogâmicos F344 , Transdução de Sinais/efeitos dos fármacos
5.
Cells ; 10(6)2021 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-34204163

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) gave rise to the coronavirus disease 2019 (COVID-19) pandemic. A strong correlation has been demonstrated between worse COVID-19 outcomes, aging, and metabolic syndrome (MetS), which is primarily derived from obesity-induced systemic chronic low-grade inflammation with numerous complications, including type 2 diabetes mellitus (T2DM). The majority of COVID-19 deaths occurs in people over the age of 65. Individuals with MetS are inclined to manifest adverse disease consequences and mortality from COVID-19. In this review, we examine the prevalence and molecular mechanisms underlying enhanced risk of COVID-19 in elderly people and individuals with MetS. Subsequently, we discuss current progresses in treating COVID-19, including the development of new COVID-19 vaccines and antivirals, towards goals to elaborate prophylactic and therapeutic treatment options in this vulnerable population.


Assuntos
Envelhecimento/fisiologia , COVID-19/prevenção & controle , COVID-19/terapia , Quimioprevenção/tendências , Síndrome Metabólica/terapia , Envelhecimento/efeitos dos fármacos , Envelhecimento/imunologia , COVID-19/diagnóstico , COVID-19/epidemiologia , Quimioprevenção/métodos , História do Século XXI , Humanos , Síndrome Metabólica/complicações , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/epidemiologia , Planejamento de Assistência ao Paciente/tendências , Prevalência , Prognóstico , Índice de Gravidade de Doença , Populações Vulneráveis
6.
Nutrients ; 13(6)2021 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-34204683

RESUMO

The average life expectancy of the world population has increased remarkably in the past 150 years and it is still increasing. A long life is a dream of humans since the beginning of time but also a dream is to live it in good physical and mental condition. Nutrition research has focused on recent decades more on food combination patterns than on individual foods/nutrients due to the possible synergistic/antagonistic effects of the components in a dietary model. Various dietary patterns have been associated with health benefits, but the largest body of evidence in the literature is attributable to the traditional dietary habits and lifestyle followed by populations from the Mediterranean region. After the Seven Countries Study, many prospective observational studies and trials in diverse populations reinforced the beneficial effects associated with a higher adherence to the Mediterranean diet in reference to the prevention/management of age-associated non-communicable diseases, such as cardiovascular and metabolic diseases, neurodegenerative diseases, cancer, depression, respiratory diseases, and fragility fractures. In addition, the Mediterranean diet is ecologically sustainable. Therefore, this immaterial world heritage constitutes a healthy way of eating and living respecting the environment.


Assuntos
Envelhecimento/fisiologia , Doença Crônica/prevenção & controle , Dieta Mediterrânea , Longevidade , Doenças não Transmissíveis/prevenção & controle , Doença Crônica/mortalidade , Dieta Mediterrânea/história , Comportamento Alimentar/fisiologia , História do Século XX , História do Século XXI , Humanos , Doenças não Transmissíveis/mortalidade
7.
Nat Commun ; 12(1): 4336, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34267196

RESUMO

Glutathione (GSH) is the most abundant cellular antioxidant. As reactive oxygen species (ROS) are widely believed to promote aging and age-related diseases, and antioxidants can neutralize ROS, it follows that GSH and its precursor, N-acetyl cysteine (NAC), are among the most popular dietary supplements. However, the long- term effects of GSH or NAC on healthy animals have not been thoroughly investigated. We employed C. elegans to demonstrate that chronic administration of GSH or NAC to young or aged animals perturbs global gene expression, inhibits skn-1-mediated transcription, and accelerates aging. In contrast, limiting the consumption of dietary thiols, including those naturally derived from the microbiota, extended lifespan. Pharmacological GSH restriction activates the unfolded protein response and increases proteotoxic stress resistance in worms and human cells. It is thus advantageous for healthy individuals to avoid excessive dietary antioxidants and, instead, rely on intrinsic GSH biosynthesis, which is fine-tuned to match the cellular redox status and to promote homeostatic ROS signaling.


Assuntos
Acetilcisteína/farmacologia , Envelhecimento/efeitos dos fármacos , Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/fisiologia , Glutationa/farmacologia , Envelhecimento/genética , Envelhecimento/fisiologia , Animais , Animais Geneticamente Modificados , Proteínas de Caenorhabditis elegans/genética , Proteínas de Ligação a DNA/genética , Suplementos Nutricionais , Escherichia coli , Feminino , Fibroblastos/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Glutationa/metabolismo , Humanos , Masculino , Paraquat/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Compostos de Sulfidrila/metabolismo , Fatores de Transcrição/genética , Resposta a Proteínas não Dobradas/fisiologia
8.
Nat Commun ; 12(1): 4343, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34267224

RESUMO

Aberrant sterol lipid metabolism is associated with physiological dysfunctions in the aging brain and aging-dependent disorders such as neurodegenerative diseases. There is an unmet demand to comprehensively profile sterol lipids spatially and temporally in different brain regions during aging. Here, we develop an ion mobility-mass spectrometry based four-dimensional sterolomics technology leveraged by a machine learning-empowered high-coverage library (>2000 sterol lipids) for accurate identification. We apply this four-dimensional technology to profile the spatially resolved landscapes of sterol lipids in ten functional regions of the mouse brain, and quantitatively uncover ~200 sterol lipids uniquely distributed in specific regions with concentrations spanning up to 8 orders of magnitude. Further spatial analysis pinpoints age-associated differences in region-specific sterol lipid metabolism, revealing changes in the numbers of altered sterol lipids, concentration variations, and age-dependent coregulation networks. These findings will contribute to our understanding of abnormal sterol lipid metabolism and its role in brain diseases.


Assuntos
Química Encefálica , Encéfalo/metabolismo , Lipídeos/química , Esteróis/análise , Envelhecimento/fisiologia , Animais , Feminino , Isomerismo , Lipidômica/métodos , Lipídeos/análise , Aprendizado de Máquina , Camundongos Endogâmicos C57BL , Esteróis/química , Esteróis/metabolismo , Espectrometria de Massas em Tandem/métodos
9.
Nat Commun ; 12(1): 3247, 2021 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-34059688

RESUMO

The Wnt signaling pathway is intricately connected with bone mass regulation in humans and rodent models. We designed an antibody-based platform that generates potent and selective Wnt mimetics. Using this platform, we engineer bi-specific Wnt mimetics that target Frizzled and low-density lipoprotein receptor-related proteins and evaluate their effects on bone accrual in murine models. These synthetic Wnt agonists induce rapid and robust bone building effects, and correct bone mass deficiency and bone defects in various disease models, including osteoporosis, aging, and long bone fracture. Furthermore, when these Wnt agonists are combined with antiresorptive bisphosphonates or anti-sclerostin antibody therapies, additional bone accrual/maintenance effects are observed compared to monotherapy, which could benefit individuals with severe and/or acute bone-building deficiencies. Our data support the continued development of Wnt mimetics for the treatment of diseases of low bone mineral density, including osteoporosis.


Assuntos
Conservadores da Densidade Óssea/farmacologia , Reabsorção Óssea/tratamento farmacológico , Fraturas do Fêmur/tratamento farmacológico , Osteoporose Pós-Menopausa/tratamento farmacológico , Proteínas Wnt/agonistas , Idoso , Envelhecimento/fisiologia , Animais , Densidade Óssea/efeitos dos fármacos , Densidade Óssea/fisiologia , Conservadores da Densidade Óssea/uso terapêutico , Reabsorção Óssea/fisiopatologia , Difosfonatos/farmacologia , Difosfonatos/uso terapêutico , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Sinergismo Farmacológico , Quimioterapia Combinada/métodos , Feminino , Fraturas do Fêmur/patologia , Fêmur/efeitos dos fármacos , Fêmur/lesões , Fêmur/patologia , Humanos , Camundongos , Osteoporose Pós-Menopausa/fisiopatologia , Via de Sinalização Wnt/efeitos dos fármacos , Adulto Jovem
10.
Clin Interv Aging ; 16: 1095-1104, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34163153

RESUMO

Purpose: Mid-upper arm circumference (MUAC) is a simple, noninvasive anthropometric indicator. This study evaluated the applicability of MUAC as an alternative screening instrument to appendicular skeletal muscle mass index (ASMI) for detecting sarcopenia, and determined the optimal MUAC cutoff values. Patients and Methods: A total of 4509 subjects ≥50 years of age from the West China Health and Aging Trend study were included in the present study. ASM was measured by bioelectrical impedance analysis. MUAC, calf circumference (CC), and grip strength were evaluated and the Short Physical Performance Battery and 3-m timed up-and-go test were administered. Low muscle mass was diagnosed based on Asian Working Group for Sarcopenia 2019 (AWGS2019) and updated European Working Group on Sarcopenia in Older People 2 (EWGSOP2) criteria. Results: ASMI was positively correlated with MUAC in both men (r=0.726, P<0.001) and women (r=0.698, P<0.001). The area under the receiver operating characteristic curve (AUC) for MUAC as an indicator of low muscle mass in men and women was 0.86 (95% confidence interval [CI]: 0.85-0.88) and 0.85 (95% CI: 0.84-0.86), respectively, according to AWGS2019 criteria; and 0.86 (95% CI: 0.85-0.88) and 0.86 (95% CI: 0.85-0.88), respectively, according to EWGSOP2 criteria. Optimal MUAC cutoff values for predicting low muscle mass were ≤28.6 cm for men and ≤27.5 cm for women. There was no significant difference between the AUCs of MUAC and CC in men according to the 2 reference standards (P=0.809), whereas the AUC of CC was superior to that of MUAC in women according to AWGS2019 (P<0.001) and EWGSOP2 (P=0.008) criteria. Conclusion: MUAC is strongly correlated with ASMI among community-dwelling middle-aged and older adults in China. MUAC can be used as a simple screening instrument to ASMI for diagnosing sarcopenia, especially in men.


Assuntos
Antropometria/métodos , Braço/fisiologia , Músculo Esquelético/fisiologia , Sarcopenia/diagnóstico , Idoso , Envelhecimento/fisiologia , Área Sob a Curva , Pesos e Medidas Corporais , China , Estudos Transversais , Feminino , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Curva ROC
11.
Methods Mol Biol ; 2277: 143-155, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34080150

RESUMO

Mice missing the Complex I subunit NADH:Ubiquinone Oxidoreductase Fe-S Protein 4 (NDUFS4) of the electron transport chain are a leading model of the severe mitochondrial disease Leigh syndrome. These mice have enabled a better understanding of mitochondrial dysfunction in human disease, as well as in the discovery of interventions that can potentially suppress mitochondrial disease manifestations. In addition, increasing evidence suggests significant overlap between interventions that increase survival in NDUFS4 knockout mice and that extend life span during normative aging. This chapter discusses the practical aspects of handling and studying these mice, which can be challenging due to their severe disease phenotype. Common procedures such as breeding, genotyping, weaning, or treating these transgenic mice are also discussed.


Assuntos
Envelhecimento/genética , Ração Animal , Complexo I de Transporte de Elétrons/genética , Camundongos Knockout , Envelhecimento/fisiologia , Animais , Feminino , Técnicas de Genotipagem , Humanos , Doença de Leigh/genética , Masculino , Doenças Mitocondriais/genética , Sirolimo/farmacologia
12.
Clin Interv Aging ; 16: 1037-1046, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34113086

RESUMO

Background: Remdesivir, an antiviral agent able to reduce inflammatory cascade accompanying severe, life-threatening pneumonia, became the first drug approved by the Food and Drug Administration for the treatment of hospitalized patients with coronavirus 2 related severe acute respiratory syndrome (SARS CoV2). As from its previously known clinical indications, the use of remdesivir in the presence of severe renal impairment is contraindicated; however, the impact of remdesivir on renal function in aging patients has not been elucidated. Subjects and Methods: This retrospective observational study involved 109 individuals consecutively admitted in internal medicine section, Azienda Ospedaliero Universitaria Pisana hospital, in November-December 2020 due to a confirmed diagnosis of SARS CoV2 and receiving remdesivir according to international inclusion criteria. Biochemical variables at admission were evaluated, together with slopes of estimated glomerular filtration rate (eGFR) built during remdesivir treatment. Participants were followed until discharge or exitus. Results: Patients were stratified according to age (80 formed the study cohort and 29 served as controls); CKD stage III was present in 46% of them. No patients showed any sign of deteriorated renal function during remdesivir. Fourteen patients in the elderly cohort deceased; their eGFR at baseline was significantly lower. Recovered patients were characterized by a relevant eGFR gaining during remdesivir treatment. Conclusion: We show here for the first time as remdesivir does not influence eGFR in a cohort of elderly people hospitalized for SARS CoV2, and that eGFR gain during such treatment is coupled with a better prognosis.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Envelhecimento/fisiologia , Alanina/análogos & derivados , Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , Monofosfato de Adenosina/efeitos adversos , Monofosfato de Adenosina/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Alanina/efeitos adversos , Alanina/uso terapêutico , Antivirais/efeitos adversos , COVID-19/mortalidade , Estudos de Coortes , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Estudos Retrospectivos , SARS-CoV-2 , Índice de Gravidade de Doença , Resultado do Tratamento
13.
Psychol Aging ; 36(4): 452-462, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34060887

RESUMO

In this study, we tested young and older adults on a spatially separated Stroop priming task in which a neutral word in colored ink (target) randomly appeared on either side of a color word in black ink (prime). Cues that preceded the target-prime word pair either indicated the correct target location (valid), the incorrect location (invalid), or provided no information about the target location (ambiguous). Analyses of proportional response latencies and ex-Gaussian parameters of response latency distributions showed that valid advance cues reduced interference and invalid cues increased interference for both young and older adults. Ambiguous cues were also associated with high levels of interference, but interference was higher for older adults than for younger adults. These findings are consistent with a large body of research showing age-related deficits in the use of the attentional network associated with executive control. However, they also demonstrate that older adults can use the attentional network associated with spatial orienting to reduce response conflict. For instance, we observed facilitation for congruent trials after the presentation of an invalid cue, but very little facilitation for congruent trials after the presentation of an ambiguous cue. As the attentional demands in our world increase, we might use this knowledge to promote optimal functioning in older adults. Our findings challenge the notion of ubiquitous age-related declines in attention and contribute to the discussion of how attentional networks work together as demands for conflict resolution vary. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Assuntos
Envelhecimento/fisiologia , Atenção/fisiologia , Teste de Stroop/normas , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
14.
Int J Mol Sci ; 22(9)2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-34063076

RESUMO

Platelet function is developmentally regulated. Healthy neonates do not spontaneously bleed, but their platelets are hypo-reactive to several agonists. The mechanisms underlying immature platelet function in neonates are incompletely understood. This critical issue remains challenging for the establishment of age-specific reference ranges. In this study, we evaluated platelet reactivity of five pediatric age categories, ranging from healthy full-term neonates up to adolescents (11-18 years) in comparison to healthy adults (>18 years) by flow cytometry. We confirmed that platelet hypo-reactivity detected by fibrinogen binding, P-selectin, and CD63 surface expression was most pronounced in neonates compared to other pediatric age groups. However, maturation of platelet responsiveness varied with age, agonist, and activation marker. In contrast to TRAP and ADP, collagen-induced platelet activation was nearly absent in neonates. Granule secretion markedly remained impaired at least up to 10 years of age compared to adults. We show for the first time that neonatal platelets are deficient in thrombospondin-1, and exogenous platelet-derived thrombospondin-1 allows platelet responsiveness to collagen. Platelets from all pediatric age groups normally responded to the C-terminal thrombospondin-1 peptide RFYVVMWK. Thus, thrombospondin-1 deficiency of neonatal platelets might contribute to the relatively impaired response to collagen, and platelet-derived thrombospondin-1 may control distinct collagen-induced platelet responses.


Assuntos
Envelhecimento/fisiologia , Plaquetas/metabolismo , Colágeno/farmacologia , Trombospondina 1/farmacologia , Difosfato de Adenosina/farmacologia , Adolescente , Adulto , Plaquetas/efeitos dos fármacos , Criança , Venenos de Crotalídeos/farmacologia , Exocitose/efeitos dos fármacos , Humanos , Lactente , Recém-Nascido , Lectinas Tipo C , Peptídeos/farmacologia , Ativação Plaquetária/efeitos dos fármacos , Receptores Ativados por Proteinase/metabolismo , Trombospondina 1/química
15.
Top Antivir Med ; 29(2): 334-343, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34107203

RESUMO

The 2021 Conference on Retroviruses and Opportunistic Infections (CROI) featured a timely review of the neurologic complications of COVID-19 as well as new research findings on mechanisms by which SARS-CoV-2 may affect the brain. CROI included new and important findings about the neurologic complications of HIV-1, human polyomavirus 2 (also known as JC Virus), and cryptococcus. New long-term analyses of cognition in people with HIV-1 identified that cognitive decline over time is associated with multimorbidity, particularly diabetes, chronic lung disease, and vascular disease risk conditions. These conditions are associated with aging, and the question of whether people with HIV are at risk for premature aging was addressed by several reports. New findings from large analyses of resting state networks also provided valuable information on the structural and functional networks that are affected by HIV-1 infection and cognitive impairment. Several reports addressed changes after initiating or switching antiretroviral therapy (ART). Findings that will improve understanding of the biologic mechanisms of brain injury in people with HIV were also presented and included evidence that host (eg, myeloid activation, inflammation, and endothelial activation) and viral (eg, transcriptional activity and compartmentalization) factors adversely affect brain health. Other research focused on adjunctive therapies to treat HIV-1 and its complications in the central nervous system. This summary will review these and other findings in greater detail and identify key gaps and opportunities for researchers and clinicians.


Assuntos
COVID-19/complicações , Infecções por HIV/complicações , HIV-1 , Doenças do Sistema Nervoso , Neuroimagem , Infecções por Retroviridae , Envelhecimento/fisiologia , Antirretrovirais/uso terapêutico , Encéfalo/fisiopatologia , Disfunção Cognitiva/fisiopatologia , Cryptococcus/isolamento & purificação , Infecções por HIV/tratamento farmacológico , Humanos , Vírus JC/isolamento & purificação , Doenças do Sistema Nervoso/epidemiologia , Doenças do Sistema Nervoso/patologia , Estados Unidos
16.
Clin Interv Aging ; 16: 1057-1070, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34135578

RESUMO

Introduction: The prevalence of metabolic syndrome among the elderly population is growing. The elements of metabolic syndrome in an aging society are currently being researched. Atherosclerosis is a slow process in which the first symptoms may be observed after many years. The mechanisms underlying the progression of atherosclerosis are oxidative stress and inflammation. Inflammation and oxidative stress are associated with the increased incidence of metabolic syndrome. Taking the above into consideration, metabolic syndrome is thought to be a clinical equivalent of atherosclerosis. Aim: The aim of this paper is to review the impact of the interplay of oxidant-antioxidant and inflammation markers in metabolic syndrome in general as well as its components in the pathophysiology which underlies development of atherosclerosis in elderly individuals. Methods: A systematic scan of online resources designed for elderly (≥65 years) published from 2005 to the end of 2020 were reviewed. This was supplemented with grey literature and then all resources were narratively analyzed. The analysis included the following terms: "atherosclerosis or metabolic syndrome" and "oxidative stress or inflammation" and "elderly" to find reports of atherosclerotic disease from asymptomatic to life-threatening among the elderly population with metabolic syndrome . Results: The work summarizes articles that were applicable to this study, including systematic reviews, qualitative studies and opinion pieces. Current knowledge focuses on monitoring the inflammation and oxidant-antioxidant imbalance in disentangling atherosclerosis in patients diagnosed with metabolic syndrome. The population-based studies described inflammation, increased oxidative stress and weak antioxidant defense systems as the mechanisms underlying atherosclerosis development. Moreover, there are discussions that these targets could potentially be a point of intervention to reduce the development of atherosclerosis in the elderly, especially those with altered glucose and lipid metabolism. Specific markers may be used as an approach for the prevention and lifestyle modification of atherosclerotic disease in such population. Conclusion: Metabolic syndrome and its components are important contributors in the progression of atherosclerotic disease in the elderly population but constant efforts should be made to broaden our knowledge of elderly groups who are the most susceptible for the development of atherosclerosis complications.


Assuntos
Antioxidantes/metabolismo , Aterosclerose/metabolismo , Inflamação/metabolismo , Síndrome Metabólica/metabolismo , Oxidantes/metabolismo , Idoso , Envelhecimento/fisiologia , Aterosclerose/fisiopatologia , Biomarcadores/metabolismo , Humanos , Inflamação/fisiopatologia , Metabolismo dos Lipídeos , Masculino , Síndrome Metabólica/fisiopatologia , Obesidade/metabolismo , Estresse Oxidativo/fisiologia
17.
Mutat Res ; 787: 108359, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34083047

RESUMO

Genome instability denotes an increased tendency to alterations in the genome during cell life cycle, driven by a large variety of endogenous and exogenous insults. Ageing is characterized by the presence of damage to various cellular constituents, but genome alterations, randomly accumulating with age in different tissues, constitute the key target in this process, and are believed to be the main factor of ageing. Age-related failure of DNA repair pathways allows DNA lesions to occur more frequently, and their accumulation over time contributes to the age-associated decrease in genome integrity in somatic cells. The micronucleus (MN) test is one of the most widely used assays to evaluate genomic instability in different surrogate tissues. A large number of studies has consistently shown a progressive increase in MN frequency with age, starting from very young age groups onwards. Therefore, MN frequency is a suitable biomarker of genomic instability in ageing. Frailty is a multidimensional geriatric syndrome of unsuccessful ageing, characterized by decreased biological reserves and increased vulnerability to external stressors, involving a higher risk of negative health outcomes. Although there is a well-founded belief that genome instability is involved in the frailty syndrome, only two studies investigated the relationship between MN frequency and frailty, not allowing to draw a definite conclusion on the utility of this biomarker for frailty detection. The use of MN and other genomic biomarkers in the detection and follow-up of patients affected by or at risk of frailty has the potential to accumulate evidence on the clinical impact of this approach in the identification and control of frailty in older people.


Assuntos
Instabilidade Genômica/genética , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/genética , Envelhecimento/fisiologia , Reparo do DNA/genética , Reparo do DNA/fisiologia , Feminino , Idoso Fragilizado , Humanos , Masculino , Testes para Micronúcleos/métodos
18.
Aging (Albany NY) ; 13(11): 14729-14744, 2021 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-34078751

RESUMO

The potential harmful effects of polypharmacy (concurrent use of 5 or more drugs) are difficult to investigate in an experimental design in humans. Moreover, there is a lack of knowledge on sex-specific differences on the outcomes of multiple-drug use. The present study aims to investigate the effects of an eight-week exposure to a regimen of five different medications (metoprolol, paracetamol, aspirin, simvastatin and citalopram) in young adult female mice. Polypharmacy-treated animals showed significant impairment in object recognition and fear associated contextual memory, together with a significant reduction of certain hippocampal proteins involved in pathways necessary for the consolidation of these types of memories, compared to animals with standard diet. The impairments in explorative behavior and spatial memory that we reported previously in young adult male mice administered the same polypharmacy regimen were not observed in females in the current study. Therefore, the same combination of medications induced different negative outcomes in young adult male and female mice, causing a significant deficit in non-spatial memory in female animals. Overall, this study strongly supports the importance of considering sex-specific differences in designing safer and targeted multiple-drug therapies.


Assuntos
Envelhecimento/fisiologia , Cognição/fisiologia , Polimedicação , Animais , Ansiedade/patologia , Comportamento Animal , Proteínas Sanguíneas/metabolismo , Peso Corporal , Dieta , Comportamento de Ingestão de Líquido , Comportamento Alimentar , Feminino , Hipocampo/metabolismo , Camundongos Endogâmicos C57BL , Atividade Motora , Memória Espacial , Fatores de Tempo
19.
Aging (Albany NY) ; 13(11): 14829-14842, 2021 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-34091440

RESUMO

Samul-tang (SM), a traditional herbal medicine, is used to treat age-related human conditions, such as infertility and menstrual irregularities. The mechanism underlying the role of SM in ovary function needs elucidation. In this study, the influence of SM administration on the ovarian reserve of aged mice was investigated. Female BALB/c mice (8 and 40 weeks-old) were administered with distilled water (young or old group) or SM for 4 weeks. SM administration prevented age-related ovarian follicle loss in mice. Quality of oocytes and blastocysts were enhanced in SM-administrated mice compared to those of non-treated old mice. Further, SM administration increased the pregnancy rate and number of litters. SM triggered changes in aging-related genes that are linked to the RAS-mediated pathway. Thus, we demonstrate that SM can be used to increase the oocyte yield in aged women, potentially improving age-related cognitive decline in the ovarian reserve.


Assuntos
Envelhecimento/fisiologia , Medicamentos de Ervas Chinesas/farmacologia , Fertilidade/efeitos dos fármacos , Ovário/fisiologia , Transdução de Sinais , Proteínas ras/metabolismo , Envelhecimento/efeitos dos fármacos , Animais , Hormônio Antimülleriano/sangue , Blastocisto/efeitos dos fármacos , Blastocisto/metabolismo , Análise por Conglomerados , Medicamentos de Ervas Chinesas/administração & dosagem , Feminino , Hormônio Foliculoestimulante/sangue , Regulação da Expressão Gênica/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Anotação de Sequência Molecular , Oócitos/efeitos dos fármacos , Oócitos/metabolismo , Folículo Ovariano/efeitos dos fármacos , Ovário/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
20.
FASEB J ; 35(8): e21743, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34192361

RESUMO

The effects of stress exposure are likely to vary depending on life-stage and stressor. While it has been postulated that mild stress exposure may have beneficial effects, the duration of such effects and the underlying mechanisms are unclear. While the long-term effects of early-life stress are relatively well studied, we know much less about the effects of exposure in adulthood since the early- and adult-life environments are often similar. We previously reported that repeated experimental exposure to a relatively mild stressor in female zebra finches, first experienced in young adulthood, initially had no effect on mortality risk, reduced mortality in middle age, but the apparently beneficial effects disappeared in old age. We show here that this is underpinned by differences between the control and stress-exposed group in the pattern of telomere change, with stress-exposed birds showing reduced telomere loss in middle adulthood. We thereby provide novel experimental evidence that telomere dynamics play a key role linking stress resilience and aging.


Assuntos
Envelhecimento/genética , Envelhecimento/fisiologia , Tentilhões/genética , Tentilhões/fisiologia , Longevidade/genética , Longevidade/fisiologia , Homeostase do Telômero/genética , Homeostase do Telômero/fisiologia , Animais , Meio Ambiente , Feminino , Tentilhões/sangue , Fatores de Risco , Estresse Fisiológico/genética , Encurtamento do Telômero/genética , Encurtamento do Telômero/fisiologia
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