Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 143
Filtrar
1.
Int J Mol Sci ; 20(17)2019 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-31480455

RESUMO

African American women are affected by earlier onset of age-associated health deteriorations and obesity disproportionally, but little is known about the mechanism linking body mass index (BMI) and biological aging among this population. DNA methylation age acceleration (DNAm AA), measuring the difference between DNA methylation age and chronological age, is a novel biomarker of the biological aging process, and predicts aging-related disease outcomes. The present study estimated cross-tissue DNA methylation age acceleration using saliva samples from 232 African American mothers. Cross-sectional regression analyses were performed to assess the association of BMI with DNAm AA. The average chronological age and DNA methylation age were 31.67 years, and 28.79 years, respectively. After adjusting for smoking, hypertension diagnosis history, and socioeconomic factors (education, marital status, household income), a 1 kg/m2 increase in BMI is associated with 0.14 years increment of DNAm AA (95% CI: (0.08, 0.21)). The conclusion: in African American women, high BMI is independently associated with saliva-based DNA methylation age acceleration, after adjusting for smoking, hypertension, and socioeconomic status. This finding supports that high BMI accelerates biological aging, and plays a key role in age-related disease outcomes among African American women.


Assuntos
Senilidade Prematura/genética , Índice de Massa Corporal , Metilação de DNA , Obesidade/genética , Adulto , Afro-Americanos/genética , Fatores Etários , Senilidade Prematura/etiologia , Estudos Transversais , Epigênese Genética , Feminino , Humanos , Mães , Obesidade/complicações , Obesidade/epidemiologia , Fatores Socioeconômicos
2.
Dev Period Med ; 23(2): 97-103, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31280245

RESUMO

Over the last decades, the overall survival rate for childhood cancer has increased from 20% to 80%, which is the result of advances in treatment. Nevertheless, most data from the international registers of childhood cancer survivors (CCS) stress that this population of patients is at high risk for late sequelae and their biological aging starts earlier in life. Anticancer therapy (chemotherapy, radiotherapy, surgery, immunotherapy) affects the intracellular processes leading to the chronic deterioration of organ function and premature senescence. The present review focuses on the late effects of anticancer treatment on various human organs that may lead to premature aging.


Assuntos
Senilidade Prematura/epidemiologia , Antineoplásicos/efeitos adversos , Sobreviventes de Câncer , Imunoterapia/efeitos adversos , Radioterapia/efeitos adversos , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Senilidade Prematura/etiologia , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Neoplasias/cirurgia , Neoplasias/terapia , Fatores de Risco
3.
Neuroimage Clin ; 22: 101764, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30904825

RESUMO

The profile of brain structural dysmorphology of individuals with Alcohol Use Disorders (AUD) involves disruption of the limbic system. In vivo imaging studies report hippocampal volume loss in AUD relative to controls, but only recently has it been possible to articulate different regions of this complex structure. Volumetric analysis of hippocampal regions rather than total hippocampal volume may augment differentiation of disease processes. For example, damage to hippocampal subfield cornu ammonis 1 (CA1) is often reported in Alzheimer's disease (AD), whereas deficits in CA4/dentate gyrus are described in response to stress and trauma. Two previous studies explored the effects of chronic alcohol use on hippocampal subfields: one reported smaller volume of the CA2+3 in alcohol-dependent subjects relative to controls, associated with years of alcohol consumption; the other, smaller volumes of presubiculum, subiculum, and fimbria in alcohol-dependent relative to control men. The current study, conducted in 24 adults with DSM5-diagnosed AUD (7 women, 53.7 ±â€¯8.8) and 20 controls (7 women, 54.1 ±â€¯9.3), is the first to use FreeSurfer 6.0, which provides state-of-the art hippocampal parcellation, to explore the sensitivity of hippocampal sufields to alcoholism. T1- and T2- images were collected on a GE MR750 system with a 32-channel Nova head coil. FreeSurfer 6.0 hippocampal subfield analysis produced 12 subfields: parasubiculum; presubiculum; subiculum; CA1; CA2+3; CA4; GC-ML-DG (Granule Cell (GC) and Molecular Layer (ML) of the Dentate Gyrus (DG)); molecular layer; hippocampus-amygdala-transition-area (HATA); fimbria; hippocampal tail; hippocampal fissure; and whole volume for left and right hippocampi. A comprehensive battery of neuropsychological tests comprising attention, memory and learning, visuospatial abilities, and executive functions was administered. Multiple regression analyses of raw volumetric data for each subfields by group, age, sex, hemisphere, and supratentorial volume (svol) showed significant effects of svol (p < .04) on nearly all structures (excluding tail and fissure). Volumes corrected for svol showed effects of age (fimbria, fissure) and group (subiculum, CA1, CA4, GC-ML-DG, HATA, fimbria); CA2+3 showed a diagnosis-by-age interaction indicating older AUD individuals had a smaller volume than would be expected for their age. There were no selective relations between hippocampal subfields and performance on neuropsychological tests, likely due to lack of statistical power. The current results concur with the previous study identifying CA2+3 as sensitive to alcoholism, extend them by identifying an alcoholism-age interaction, and suggest an imaging phenotype distinguishing AUD from AD and stress/trauma.


Assuntos
Senilidade Prematura/patologia , Alcoolismo/patologia , Região CA2 Hipocampal/patologia , Região CA3 Hipocampal/patologia , Adulto , Idoso , Senilidade Prematura/diagnóstico por imagem , Senilidade Prematura/etiologia , Alcoolismo/complicações , Alcoolismo/diagnóstico por imagem , Alcoolismo/fisiopatologia , Região CA2 Hipocampal/diagnóstico por imagem , Região CA3 Hipocampal/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
4.
Viruses ; 11(3)2019 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-30818749

RESUMO

Despite effective antiretroviral therapy (ART), people living with HIV (PLWH) still present persistent chronic immune activation and inflammation. This condition is the result of several factors including thymic dysfunction, persistent antigen stimulation due to low residual viremia, microbial translocation and dysbiosis, caused by the disruption of the gut mucosa, co-infections, and cumulative ART toxicity. All of these factors can create a vicious cycle that does not allow the full control of immune activation and inflammation, leading to an increased risk of developing non-AIDS co-morbidities such as metabolic syndrome and cardiovascular diseases. This review aims to provide an overview of the most recent data about HIV-associated inflammation and chronic immune exhaustion in PLWH under effective ART. Furthermore, we discuss new therapy approaches that are currently being tested to reduce the risk of developing inflammation, ART toxicity, and non-AIDS co-morbidities.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Comorbidade , Infecções por HIV/complicações , Inflamação , Senilidade Prematura/etiologia , Fármacos Anti-HIV/uso terapêutico , Doenças Cardiovasculares/etiologia , Infecções por HIV/imunologia , Infecções por HIV/patologia , Humanos , Ativação Linfocitária , Síndrome Metabólica/etiologia
5.
Aging (Albany NY) ; 10(11): 3610-3625, 2018 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-30418933

RESUMO

BACKGROUND: Premature aging and related diseases have been documented in HIV-infected adults. Data are now emerging also regarding accelerated aging process in HIV-infected children. METHODS: A narrative review was performed searching studies on PubMed published in English language in 2004-2017, using appropriate key words, including "aging", "children", "HIV", "AIDS", "immunosenescence", "pathogenesis", "clinical conditions". RESULTS: Premature immunosenescence phenotype of B and T cells in HIV-infected children is mediated through immune system activation and chronic inflammation. Ongoing inflammation processes have been documented by increased levels of pathogen-associated molecular patterns (PAMPS), increased mitochondrial damage, higher levels of pro-inflammatory cytokines, and a positive correlation between sCD14 levels and percentages of activated CD8+ cells. Other reported features of premature aging include cellular replicative senescence, linked to an accelerated telomeres shortening. Finally, acceleration of age-associated methylation pattern and other epigenetic modifications have been described in HIV-infected children. All these features may favor the clinical manifestations related to premature aging. Lipid and bone metabolism, cancers, cardiovascular, renal, and neurological systems should be carefully monitored, particularly in children with detectable viremia and/or with CD4/CD8 ratio inversion. CONCLUSION: Aging processes in children with HIV infection impact their quality and length of life. Further studies regarding the mechanisms involved in premature aging are needed to search for potential targets of treatment.


Assuntos
Senilidade Prematura/etiologia , Infecções por HIV/complicações , Senilidade Prematura/metabolismo , Criança , Infecções por HIV/metabolismo , Infecções por HIV/patologia , Humanos , Imunossenescência , Inflamação/complicações
6.
J Clin Oncol ; 36(21): 2206-2215, 2018 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-29874132

RESUMO

The improvement in survival of childhood cancer observed across the past 50 years has resulted in a growing acknowledgment that simply extending the lifespan of survivors is not enough. It is incumbent on both the cancer research and the clinical care communities to also improve the health span of survivors. It is well established that aging adult survivors of childhood cancer are at increased risk of chronic health conditions, relative to the general population. However, as the first generation of survivors age into their 50s and 60s, it has become increasingly evident that this population is also at risk of early onset of physiologic aging. Geriatric measures have uncovered evidence of reduced strength and speed and increased fatigue, all components of frailty, among survivors with a median age of 33 years, which is similar to adults older than 65 years of age in the general population. Furthermore, frailty in survivors independently increased the risk of morbidity and mortality. Although there has been a paucity of research investigating the underlying biologic mechanisms for advanced physiologic age in survivors, results from geriatric populations suggest five biologically plausible mechanisms that may be potentiated by exposure to cancer therapies: increased cellular senescence, reduced telomere length, epigenetic modifications, somatic mutations, and mitochondrial DNA infidelity. There is now a critical need for research to elucidate the biologic mechanisms of premature aging in survivors of childhood cancer. This research could pave the way for new frontiers in the prevention of these life-changing outcomes.


Assuntos
Senilidade Prematura/etiologia , Sobreviventes de Câncer , Longevidade , Neoplasias/mortalidade , Senilidade Prematura/mortalidade , Senilidade Prematura/fisiopatologia , Criança , Humanos , Neoplasias/fisiopatologia , Risco
7.
Annu Rev Clin Psychol ; 14: 371-397, 2018 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-29494257

RESUMO

Telomeres play an important part in aging and show relationships to lifetime adversity, particularly childhood adversity. Meta-analyses demonstrate reliable associations between psychopathology (primarily depression) and shorter telomere length, but the nature of this relationship has not been fully understood. Here, we review and evaluate the evidence for impaired telomere biology as a consequence of psychopathology or as a contributing factor, and the important mediating roles of chronic psychological stress and impaired allostasis. There is evidence for a triadic relationship among stress, telomere shortening, and psychiatric disorders that is positively reinforcing and unfolds across the life course and, possibly, across generations. We review the role of genetics and biobehavioral responses that may contribute to shorter telomere length, as well as the neurobiological impact of impaired levels of telomerase. These complex interrelationships are important to elucidate because they have implications for mental and physical comorbidity and, potentially, for the prevention and treatment of depression.


Assuntos
Experiências Adversas da Infância , Senilidade Prematura , Transtornos Mentais , Estresse Psicológico , Telomerase , Encurtamento do Telômero , Senilidade Prematura/etiologia , Senilidade Prematura/genética , Senilidade Prematura/metabolismo , Animais , Humanos , Transtornos Mentais/etiologia , Transtornos Mentais/genética , Transtornos Mentais/metabolismo , Estresse Psicológico/complicações , Estresse Psicológico/genética , Estresse Psicológico/metabolismo , Telomerase/metabolismo , Encurtamento do Telômero/genética
8.
J Gerontol A Biol Sci Med Sci ; 73(9): 1187-1196, 2018 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-29415134

RESUMO

HIV-1 causes premature aging in chronically infected patients. Despite effective anti-retroviral therapy, around 50% of patients suffer HIV-associated neurocognitive disorders (HAND), which likely potentiate aging-associated neurocognitive decline. Microglia support productive HIV-1 infection in the brain. Elevated markers of cellular senescence, including p53 and p21, have been detected in brain tissues from patients with HAND, but the potential for microglia senescence during HIV-1 infection has not been investigated. We hypothesized that HIV-1 can induce senescence in microglia. Primary human fetal microglia were exposed to single-round infectious HIV-1 pseudotypes or controls, and examined for markers of senescence. Post-infection, microglia had significantly elevated: senescence-associated ß-galactosidase activity, p21 levels, and production of cytokines such as IL-6 and IL-8, potentially indicative of a senescence-associated secretory phenotype. We also found increased detection of p53-binding protein foci in microglia nuclei post-infection. Additionally, we examined mitochondrial reactive oxygen species (ROS) and respiration, and found significantly increased mitochondrial ROS levels and decreased ATP-linked respiration during HIV-1 infection. Supernatant transfer from infected cultures to naïve microglia resulted in elevated p21 and caveolin-1 levels, and IL-8 production. Finally, nucleoside treatment reduced senescence markers induction in microglia. Overall, HIV-1 induces a senescence-like phenotype in human microglia, which could play a role in HAND.


Assuntos
Senilidade Prematura , Senescência Celular/fisiologia , Infecções por HIV , Microglia/metabolismo , Senilidade Prematura/etiologia , Senilidade Prematura/metabolismo , Células Cultivadas , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Infecções por HIV/complicações , Infecções por HIV/metabolismo , HIV-1/fisiologia , Humanos , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Mitocôndrias/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , beta-Galactosidase/metabolismo
9.
Rev Esp Geriatr Gerontol ; 53(2): 105-110, 2018.
Artigo em Espanhol | MEDLINE | ID: mdl-28601217

RESUMO

The HIV-infected population is aging due to the success of combination antiretroviral therapy, which prolongs survival, as well as the growing number of newly diagnosed cases in adults 50 years old and over. HIV-infected individuals suffer from an accelerated aging due to the persistent and chronic activation of the immune system that leads to immune exhaustion and accelerated immunosenescence, even when on optimal immuno-virological control treatment. The clinical expression of the immunosenescence state is an increased prevalence of aging-related non-HIV associated comorbidities and a rising prevalence of frailty occurring earlier than in the general population. Thus, HIV-infected patients are biologically older than their chronological age, and they suffer from aging-related problems, such as frailty, which should be assessed.


Assuntos
Senilidade Prematura/etiologia , Fragilidade/etiologia , Infecções por HIV/complicações , Idoso , Humanos , Imunossenescência
10.
Probl Radiac Med Radiobiol ; 22: 38-68, 2017 Dec.
Artigo em Inglês, Ucraniano | MEDLINE | ID: mdl-29286496

RESUMO

The article provides an overview of modern physiological evidence to support the hypothesis on cortico limbic sys tem dysfunction due to the hippocampal neurogenesis impairment as a basis of the brain interhemispheric asym metry and neurocognitive deficit after radiation exposure. The importance of the research of both evoked poten tials and fields as a highly sensitive and informative method is emphasized.Particular attention is paid to cerebral sensor systems dysfunction as a typical effect of ionizing radiation. Changes in functioning of the central parts of sensory analyzers of different modalities as well as the violation of brain integrative information processes under the influence of small doses of ionizing radiation can be critical when determining the radiation risks of space flight. The possible long term prospects for manned flights into space, including to Mars, given the effects identified are discussed. Potential risks to the central nervous system during space travel comprise cognitive functions impairment, including the volume of short term memory short ening, impaired motor functions, behavioral changes that could affect human performance and health. The remote risks for CNS are considered to be the following possible neuropsychiatric disorders: accelerated brain aging, Alzheimer's disease and other types of dementia. The new radiocerebral dose dependent effect, when applied cog nitive auditory evoked potentials P300 technique with a possible threshold dose of 0.05 Gy, manifesting in a form of disruption of information processing in the Wernicke's area is under discussion. In order to identify neurophys iological biological markers of ionizing radiation further international researches with adequate dosimetry support are necessary.


Assuntos
Senilidade Prematura/etiologia , Córtex Cerebral/efeitos da radiação , Sistema Límbico/efeitos da radiação , Transtornos Neurocognitivos/etiologia , Transtornos Psicomotores/etiologia , Exposição à Radiação/efeitos adversos , Senilidade Prematura/diagnóstico , Senilidade Prematura/fisiopatologia , Córtex Cerebral/fisiopatologia , Cognição/fisiologia , Cognição/efeitos da radiação , Radiação Cósmica/efeitos adversos , Potenciais Evocados/fisiologia , Potenciais Evocados/efeitos da radiação , Humanos , Sistema Límbico/fisiopatologia , Memória de Curto Prazo/fisiologia , Memória de Curto Prazo/efeitos da radiação , Transtornos Neurocognitivos/diagnóstico , Transtornos Neurocognitivos/fisiopatologia , Transtornos Psicomotores/diagnóstico , Transtornos Psicomotores/fisiopatologia , Radiação Ionizante , Voo Espacial
11.
Int J Mol Sci ; 18(11)2017 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-29072584

RESUMO

Chronic high caloric intake (HCI) is a risk factor for multiple major human disorders, from diabetes to neurodegeneration. Mounting evidence suggests a significant contribution of circadian misalignment and sleep alterations to this phenomenon. An inverse temporal relationship between sleep, activity, food intake, and clock mechanisms in nocturnal and diurnal animals suggests that a search for effective therapeutic approaches can benefit from the use of diurnal animal models. Here, we show that, similar to normal aging, HCI leads to the reduction in daily amplitude of expression for core clock genes, a decline in sleep duration, an increase in scoliosis, and anxiety-like behavior. A remarkable decline in adult neurogenesis in 1-year old HCI animals, amounting to only 21% of that in age-matched Control, exceeds age-dependent decline observed in normal 3-year old zebrafish. This is associated with misalignment or reduced amplitude of daily patterns for principal cell cycle regulators, cyclins A and B, and p20, in brain tissue. Together, these data establish HCI in zebrafish as a model for metabolically induced premature aging of sleep, circadian functions, and adult neurogenesis, allowing for a high throughput approach to mechanistic studies and drug trials in a diurnal vertebrate.


Assuntos
Senilidade Prematura/etiologia , Ritmo Circadiano , Neurogênese , Transtornos do Sono-Vigília/complicações , Transtornos do Sono-Vigília/fisiopatologia , Sono , Animais , Ansiedade , Peso Corporal , Encéfalo/metabolismo , Encéfalo/patologia , Encéfalo/fisiopatologia , Relógios Circadianos , Ingestão de Energia , Expressão Gênica , Tamanho do Órgão , Peixe-Zebra
12.
Indian J Gastroenterol ; 36(4): 323-325, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28795391

RESUMO

Werner syndrome is a rare progeroid syndrome caused by the WRN gene mutation. It is characterized by a general appearance of premature aging, diabetes mellitus, and atherosclerosis, and an increased risk of malignancies. We report a patient who presented with hematemesis due to cirrhosis of liver and was subsequently diagnosed with Werner syndrome. Further genetic analysis showed a novel mutation in the WRN gene which has not previously been reported. Werner syndrome should be considered for the cases of liver cirrhosis when accompanied by the features of accelerated aging.


Assuntos
Estudos de Associação Genética , Cirrose Hepática/etiologia , Mutação , Helicase da Síndrome de Werner/genética , Síndrome de Werner/complicações , Síndrome de Werner/genética , Adulto , Senilidade Prematura/etiologia , Hematemese/etiologia , Humanos , Masculino , Síndrome de Werner/diagnóstico
13.
Free Radic Biol Med ; 108: 300-310, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28315451

RESUMO

Skin damage from exposure to sunlight induces aging-like changes in appearance and is attributed to the ultraviolet (UV) component of light. Photosensitized production of reactive oxygen species (ROS) by UVA light is widely accepted to contribute to skin damage and carcinogenesis, but visible light is thought not to do so. Using mice expressing redox-sensitive GFP to detect ROS, blue light could produce oxidative stress in live skin. Blue light induced oxidative stress preferentially in mitochondria, but green, red, far red or infrared light did not. Blue light-induced oxidative stress was also detected in cultured human keratinocytes, but the per photon efficacy was only 25% of UVA in human keratinocyte mitochondria, compared to 68% of UVA in mouse skin. Skin autofluorescence was reduced by blue light, suggesting flavins are the photosensitizer. Exposing human skin to the blue light contained in sunlight depressed flavin autofluorescence, demonstrating that the visible component of sunlight has a physiologically significant effect on human skin. The ROS produced by blue light is probably superoxide, but not singlet oxygen. These results suggest that blue light contributes to skin aging similar to UVA.


Assuntos
Senilidade Prematura/metabolismo , Queratinócitos/efeitos da radiação , Luz/efeitos adversos , Mitocôndrias/efeitos da radiação , Estresse Oxidativo , Pele/efeitos da radiação , Senilidade Prematura/etiologia , Animais , Células Cultivadas , Humanos , Queratinócitos/fisiologia , Camundongos , Camundongos Pelados , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mitocôndrias/metabolismo , Oxirredução , Pele/patologia , Superóxidos/química , Superóxidos/metabolismo
14.
Am J Addict ; 26(2): 129-135, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28106943

RESUMO

BACKGROUND AND OBJECTIVES: Smoking is known to increase biological age. However, whether this process is reversible through smoking cessation is not known. In this pilot study, we attempt to determine whether smoking cessation reduces biological age. METHODS: We conducted regression analyses of methylation data from 22 subjects, as they entered and exited inpatient substance use treatment, to determine change in biological age, as indicated by the deviation of their methylomic age from chronological age across two time points. RESULTS: We found that, as compared to those subjects who did not stop smoking, subjects who significantly decreased their smoking consumption over a 1 month time period exhibited a marked reduction in methylomic age. CONCLUSION: The rapid and substantial reversal of accelerated aging associated with successful smoking cessation suggests that it can reverse well-known smoking effects on methylomic aging. This preliminary finding can be readily examined in other, larger data sets, and if replicated, this observation may provide smokers with yet another good reason to quit smoking. SCIENTIFIC SIGNIFICANCE: Successful smoking cessation makes patients appear biologically younger than they were at baseline, and to do so quite rapidly. In today's youth driven society, our observations may serve as a powerful impetus for some to quit smoking. (Am J Addict 2017;26:129-135).


Assuntos
Senilidade Prematura , Envelhecimento , Motivação , Abandono do Hábito de Fumar/psicologia , Fumar , Envelhecimento/fisiologia , Envelhecimento/psicologia , Senilidade Prematura/etiologia , Senilidade Prematura/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Aparência Física/fisiologia , Projetos Piloto , Análise de Regressão , Fumar/efeitos adversos , Fumar/fisiopatologia , Fumar/psicologia , Fumar/terapia
15.
Virulence ; 8(5): 599-604, 2017 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-27435879

RESUMO

BACKGROUND: The prevalence of neurocognitive deficits are reported to be high in HIV-1 positive patients, even with suppressive antiretroviral treatment, and it has been suggested that HIV can cause accelerated aging of the brain. In this study we measured phosphorylated tau (p-tau) in cerebrospinal fluid (CSF) as a potential marker for premature central nervous system (CNS) aging. P-tau increases with normal aging but is not affected by HIV-associated neurocognitive disorders. METHODS: With a cross-sectional retrospective design, p-tau, total tau (t-tau), neopterin and HIV-RNA were measured in CSF together with plasma HIV-RNA and blood CD4+ T-cells of 225 HIV-infected patients <50 y of age, subdivided into 3 groups: untreated neuroasymptomatic (NA) (n = 145), on suppressive antiretroviral treatment (cART) (n = 49), and HIV-associated dementia (HAD) (n = 31). HIV-negative healthy subjects served as controls (n = 79). RESULTS: P-tau was not significantly higher in any HIV-infected group compared to HIV-negative controls. Significant increases in t-tau were found as expected in patients with HAD compared to NA, cART, and control groups (p < 0.001 ). CONCLUSIONS: P-tau was not higher in HIV-infected patients compared to uninfected controls, thus failing to support a role for premature or accelerated brain aging in HIV infection.


Assuntos
Senilidade Prematura/fisiopatologia , Infecções por HIV/complicações , Infecções por HIV/fisiopatologia , Proteínas tau/líquido cefalorraquidiano , Complexo AIDS Demência/líquido cefalorraquidiano , Complexo AIDS Demência/diagnóstico , Adulto , Senilidade Prematura/diagnóstico , Senilidade Prematura/etiologia , Terapia Antirretroviral de Alta Atividade , Biomarcadores/líquido cefalorraquidiano , Encéfalo/patologia , Encéfalo/virologia , Estudos de Coortes , Estudos Transversais , Feminino , HIV/isolamento & purificação , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Neopterina/líquido cefalorraquidiano , Fosforilação , RNA Viral/sangue , RNA Viral/líquido cefalorraquidiano , Estudos Retrospectivos , Proteínas tau/sangue , Proteínas tau/química
16.
Curr Aging Sci ; 10(1): 26-31, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27719627

RESUMO

Industrial xenobitics, as well as endogenous damaging factors, such as L-homocysteine, are a well-known source of reactive oxygen species that disrupt biological processes. Among many others, luteinizing hormone releasing hormone synthesis and secretion mediated by a variety of neurotransmitters, which are under control of the hypothalamus and pineal gland, may be put in peril by reactive oxygen species. Their formation can be one of the reasons for the reproductive function shutdown in ageing as the generic response to the damaging factors independent of their nature. We review recent findings demonstrating the role of reactive oxygen species in disrupting the circadian signal originated in the main pacemaker of the organism, the suprachiasmatic nuclei of the hypothalamus, on its way to the hypothalamic areas responsible for the luteinizing hormone preovulatory surge.


Assuntos
Senilidade Prematura/etiologia , Senilidade Prematura/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Reprodução/fisiologia , Animais , Feminino , Humanos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/metabolismo , Melatonina/metabolismo , Melatonina/farmacologia , Fármacos Neuroprotetores/metabolismo , Fármacos Neuroprotetores/farmacologia , Neurotoxinas/metabolismo , Neurotoxinas/toxicidade , Reprodução/efeitos dos fármacos
17.
J Clin Oncol ; 35(2): 149-156, 2017 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-27893337

RESUMO

Purpose The sequelae of cancer treatment may increase systemic inflammation and create a phenotype at increased risk of functional decline and comorbidities, leading to premature mortality. Little is known about how this trajectory compares with natural aging among peers of the same age without cancer. This longitudinal study investigated proinflammatory cytokines and comorbidity development over time among breast cancer survivors and a noncancer control group. Methods Women (N = 315; 209 with breast cancer and 106 in the control group) were recruited at the time of their work-up for breast cancer; they completed the baseline questionnaire, interview, and blood draw (lipopolysaccharide-stimulated production of interleukin [IL] -6, tumor necrosis factor-α, and IL-1ß). Measures were repeated 6 and 18 months after primary cancer treatment (cancer survivors) or within a comparable time frame (control group). Results There were no baseline differences in comorbidities or cytokines between survivors and the control group. Over time, breast cancer survivors had significantly higher tumor necrosis factor-α and IL-6 compared with the control group. Survivors treated with surgery, radiation, and chemotherapy accumulated a significantly greater burden of comorbid conditions and suffered greater pain associated with inflammation over time after cancer treatment than did the control group. Conclusion Survivors who had multimodal treatment had higher cytokines and comorbidities, suggestive of accelerated aging. Comorbidities were related to inflammation in this sample, which could increase the likelihood of premature mortality. Given that many comorbidities take years to develop, future research with extended follow-up beyond 18 months is necessary to examine the evidence of accelerated aging in cancer survivors and to determine the responsible mechanisms.


Assuntos
Senilidade Prematura/etiologia , Neoplasias da Mama/terapia , Neoplasias da Mama/sangue , Neoplasias da Mama/complicações , Neoplasias da Mama/mortalidade , Terapia Combinada , Comorbidade , Citocinese/fisiologia , Feminino , Humanos , Interleucina-1beta/sangue , Interleucina-6/sangue , Estudos Longitudinais , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/sangue
18.
J Pharmacol Exp Ther ; 360(3): 388-398, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28011874

RESUMO

UVA irradiation plays a role in premature aging of the skin through triggering oxidative stress-associated stimulation of matrix metalloproteinase-1 (MMP-1) responsible for collagen degradation, a hallmark of photoaged skin. Compounds that can activate nuclear factor E2-related factor 2 (Nrf2), a transcription factor regulating antioxidant gene expression, should therefore serve as effective antiphotoaging agents. We investigated whether genetic silencing of Nrf2 could relieve UVA-mediated MMP-1 upregulation via activation of mitogen-activated protein kinase (MAPK)/activator protein 1 (AP-1) signaling using human keratinocyte cell line (HaCaT). Antiphotoaging effects of hispidulin (HPD) and sulforaphane (SFN) were assessed on their abilities to activate Nrf2 in controlling MMP-1 and collagen expressions in association with phosphorylation of MAPKs (extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38), c-Jun, and c-Fos, using the skin of BALB/c mice subjected to repetitive UVA irradiation. Our findings suggested that depletion of Nrf2 promoted both mRNA expression and activity of MMP-1 in the UVA-irradiated HaCaT cells. Treatment of Nrf2 knocked-down HaCaT cells with MAPK inhibitors significantly suppressed UVA-induced MMP-1 and AP-1 activities. Moreover, pretreatment of the mouse skin with HPD and SFN, which could activate Nrf2, provided protective effects against UVA-mediated MMP-1 induction and collagen depletion in correlation with the decreased levels of phosphorylated MAPKs, c-Jun, and c-Fos in the mouse skin. In conclusion, Nrf2 could influence UVA-mediated MMP-1 upregulation through the MAPK/AP-1 signaling cascades. HPD and SFN may therefore represent promising antiphotoaging candidates.


Assuntos
Colágeno/metabolismo , Flavonas/farmacologia , Isotiocianatos/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Envelhecimento da Pele , Raios Ultravioleta/efeitos adversos , Senilidade Prematura/etiologia , Senilidade Prematura/metabolismo , Animais , Antimutagênicos/farmacologia , Linhagem Celular , Ativação Enzimática/efeitos da radiação , Humanos , Queratinócitos , Sistema de Sinalização das MAP Quinases/efeitos da radiação , Metaloproteinase 1 da Matriz/metabolismo , Camundongos , Estresse Oxidativo , Pele/metabolismo , Envelhecimento da Pele/efeitos dos fármacos , Envelhecimento da Pele/efeitos da radiação , Fator de Transcrição AP-1/metabolismo , Regulação para Cima/efeitos da radiação
20.
Neurobiol Learn Mem ; 133: 157-170, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27246251

RESUMO

Both chronological aging and chronic hypoxia stress have been reported to cause degeneration of hippocampal CA3 neurons and spatial memory impairment through independent pathways. However, the possible occurrence of precocious biological aging on exposure to single episode of global hypoxia resulting in impairment of learning and memory remains to be established. The present study thus aimed at bridging this gap in existing literature on hypoxia induced biological aging. Male Sprague Dawley rats were exposed to simulated hypobaric hypoxia (25,000ft) for different durations and were compared with aged rats. Behavioral studies in Morris Water Maze showed decline in learning abilities of both chronologically aged as well as hypoxic rats as evident from increased latency and pathlength to reach target platform. These behavioral changes in rats exposed to global hypoxia were associated with deposition of lipofuscin and ultrastructural changes in the mitochondria of hippocampal neurons that serve as hallmarks of aging. A single episode of chronic hypobaric hypoxia exposure also resulted in the up-regulation of pro-aging protein, S100A9 and down regulation of Tau, SNAP25, APOE and Sod2 in the hippocampus similar to that in aged rats indicating hypoxia induced accelerated aging. The present study therefore provides evidence for role of biological aging of hippocampal neurons in hypoxia induced impairment of learning and memory.


Assuntos
Senilidade Prematura/etiologia , Envelhecimento/fisiologia , Comportamento Animal/fisiologia , Disfunção Cognitiva/etiologia , Hipocampo/metabolismo , Hipóxia/complicações , Aprendizagem em Labirinto/fisiologia , Memória Espacial/fisiologia , Envelhecimento/metabolismo , Senilidade Prematura/metabolismo , Senilidade Prematura/patologia , Senilidade Prematura/fisiopatologia , Animais , Disfunção Cognitiva/fisiopatologia , Hipocampo/patologia , Masculino , Ratos , Ratos Sprague-Dawley
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA