Estratégias anti-aging baseadas em moléculas químicas naturais como potentes ativadores de telomerase / Anti-aging strategies based on natural chemical molecules as potent telomerase activators / Estrategias antienvejecimiento basadas en moléculas químicas naturales como potentes activadores de la telomerasa

Mesmo em tempos modernos, os grandes avanços tecnológicos não permitem de forma comprovada retardar o envelhecimento nos seres humanos. Neste sentido, uma das estratégias é o uso moléculas químicas naturais que possuem a ação de ativadores de telomerase, uma vez de que a telomerase é uma ribonucleoproteína transcriptase reversa que possui a função de alongar os telômeros e neutralizar a erosão normal dos telômeros. Neste contexto, este estudo de revisão dedicou-se a aprofundar o conhecimento sobre o uso de moléculas químicas naturais derivadas de plantas que possuem função de ativadores de telomerase para atividade anti-aging. Inúmeras moléculas têm sido propostas e, estudas os seus mecanismos com o intuito de desenvolver novas ferramentas para prevenir/retardar e tratar doenças relacionadas a idade e o envelhecimento. Adicionalmente, o uso de moléculas como ativadores da telomerase têm sido um meio de prolongar o encurtamento dos temoleros, como no caso, de moléculas isolada da erva Astragalus membranaceus (TA-65), curcumina, silbinina e alicina; ademais, outras moléculas de origem natural possuem atividade anti-aging comprovadas, conforme reportadas nesta revisão. Sendo assim, a procura por biomarcadores à base de compostos químicos naturais que estimulem a telomerase, a fim de prolongar a vida dos telômero e assim, retardar o processo de envelhecimento do organismo têm despertado o interesse de diversos pesquisadores ao redor do mundo.

Even in modern times, the great technological advances do not allow in a proven way to delay aging in humans. In this sense, one of the strategies is the use of natural chemical molecules that have telomerase activators, since telomerase is a ribonucleoprotein reverse transcriptase that has the function of lengthening telomeres and neutralizing the normal erosion of telomeres. In this context, this review study was dedicated to deepening the knowledge about the use of natural chemical molecules derived from plants that have telomerase activator function for anti-aging activity. Numerous molecules have been proposed and their mechanisms studied in order to develop new tools to prevent/delay and treat aging-related diseases. Additionally, the use of molecules as telomerase activators has been a means of prolonging the shortening of temolers, as in the case of molecules isolated from the herb Astragalus membranaceus (TA-65), curcumin, silbinin and allicin; in addition, other molecules of natural origin have proven anti-aging activity, as reported in this review. Therefore, the search for biomarkers based on natural chemical compounds that stimulate telomerase in order to prolong the life of telomeres and, thus delay the aging process of the organism has aroused the interest of several researchers around the world.

Aún en los tiempos modernos, los grandes avances tecnológicos no permiten de manera comprobada retrasar el envejecimiento en los humanos. En este sentido, una de las estrategias es el uso de moléculas químicas naturales que tengan activadores de la telomerasa, ya que la telomerasa es una ribonucleoproteína transcriptasa inversa que tiene la función de alargar los telómeros y neutralizar la erosión normal de los telómeros. En este contexto, este estudio de revisión se dedicó a profundizar en el conocimiento sobre el uso de moléculas químicas naturales derivadas de plantas que tienen función activadora de la telomerasa para la actividad antienvejecimiento. Se han propuesto numerosas moléculas y se han estudiado sus mecanismos para desarrollar nuevas herramientas para prevenir/retrasar y tratar enfermedades relacionadas con el envejecimiento. Adicionalmente, el uso de moléculas como activadores de la telomerasa ha sido un medio para prolongar el acortamiento de temolers, como es el caso de moléculas aisladas de la hierba Astragalus membranaceus (TA-65), curcumina, silbinina y alicina; además, otras moléculas de origen natural han demostrado actividad antienvejecimiento, como se reporta en esta revisión. Por ello, la búsqueda de biomarcadores basados en compuestos químicos naturales que estimulen la telomerasa para prolongar la vida de los telómeros y así retrasar el proceso de envejecimiento del organismo ha despertado el interés de varios investigadores a nivel mundial.

Polifarmácia e fatores associados em idosos diabéticos / Polypharmacy and associated factors in elderly diabetic / Factores asociados con la polifarmacia en los ancianos diabéticos

RESUMO Objetivos Objetivou-se no presente estudo analisar os fatores associados à polimedicação, bem como, a utilização de medicamentos potencialmente inapropriados (MPI) em idosos diabéticos. Metodologia Foram avaliados 127 idosos com diagnóstico de diabetes mellitus tipo 2, sendo 41 do sexo masculino (idade = 69,9 ± 6,9 anos) e 86 do sexo feminino (idade = 71,1 ± 7,7 anos). Para avaliação das condições de saúde, uso de medicamentos, polimedicação e fatores associados, utilizou-se o questionário adaptado de Morais. Os medicamentos foram classificados de acordo com a Anatomical-Therapeutical-Chemical Classification System e para identificação dos MPI, adotou-se os critérios de Beers-Fick e PRISCUS. Para análise dos dados utilizou-se a estatística descritiva e os testes qui-quadrado de Pearson e Exato de Fisher. Resultados Na população estudada constatou-se que 100% utilizava medicamentos. O consumo médio foi de 5,8 fármacos por indivíduo, variando de 2 a 14, com uma prevalência de polifarmácia de 85%. Dentre os fatores estudados, apenas a aposentadoria apresentou uma associação estatisticamente significante (p<0,05) com a polimedicação. As patologias mais prevalentes foram: hipertensão arterial (92,8%), problemas cardíacos (70,8%), circulatórios (40,8%) e problemas osteoarticulares (44,5%). Dos fármacos utilizados pelos idosos, 12 deles foram considerados potencialmente inapropriados e 47,2% dos sujeitos estudados fazem uso destes medicamentos regularmente. Conclusão Desta forma, este estudo instiga novas formas de pensar a Assistência Farmacêutica, como uma prática vista sob a ótica integral e não pensada somente como compra e dispensação de medicamentos.(AU)

ABSTRACT Objectives The objective of this study was to evaluate factors related to polypharmacy and the use of potentially inappropriate medications (PIM) in elderly patients with diabetes. Methods We studied 127 elderly diagnosed with type 2 diabetes, 41 males (age = 69.9 ± 6.9 years) and 86 women (age = 71.1 ± 7.7 years). For evaluation of health conditions, medication use, polypharmacy and associated factors, we used the questionnaire adapted from Morais. The drugs were classified according to the Anatomical Therapeutic-Chemical Classification System, and for identification of MPI, we adopted the criteria of Beers-Fick and PRISCUS. For data analysis, we used descriptive statistics and chi-square and Fisher Exact tests. Results In this population, 100% of elderly using drugs. The average consumption was 5.8 per individual drug, varying from two to 14, and the prevalence of polypharmacy was 85%. Among the factors studied, only the retirement showed a statistically significant association (p <0.05) with polypharmacy. The most prevalent diseases were hypertension (92.8%), heart problems (70.8%), circulatory (40.8%) and musculoskeletal problems (44.5%). Of drugs used by the elderly, 12 of them were considered potentially inappropriate and 47.2% of the study subjects make use of these medicines regularly. Conclusions Thus, this study urges new thinking pharmaceutical assistance, as a practical view in full perspective and not meant only as purchasing and dispensing drugs.(AU)

RESUMEN Objetivos El objetivo de este estudio fue evaluar los factores asociados a la polifarmacia y el uso de medicamentos potencialmente inapropiados (MPI) en ancianos con diabetes. Métodos Se estudiaron 41 varones (edad = 69,9 ± 6,9 años) y 86 mujeres (edad = 71,1 ± 7,7 años), diagnosticados con diabetes tipo 2. Para la evaluación de las condiciones de salud, uso de medicamentos, polifarmacia y factores asociados, se utilizó el cuestionario adaptado de Morais. Los fármacos se clasificaron de acuerdo con el Sistema de Clasificación Terapéutico-Químico y Anatómico y para identificar el MPI adoptamos los criterios de Beers-Fick y Prisco. Para el análisis de datos utilizamos estadística descriptiva y pruebas de chi-cuadrado de Pearson y Test Exacto de Fisher. Resultados Toda la población estudiada usaban medicación. El consumo promedio fue de 5,8 fármacos por persona, desde 2 a 14, con una prevalencia de polifarmacia de 85%. Entre los factores estudiados, sólo el retiro o jubilación mostró una asociación estadísticamente significativa (p<0,05) con la polifarmacia. Las enfermedades más prevalentes fueron: hipertensión arterial (92,8%), problemas cardíacos (70,8%), circulatorios (40,8%) y problemas osteoarticulares (44,5%). Doce de los medicamentos utilizada por ancianos fueron considerados potencialmente inapropiados y el 47,2% de los sujetos del estudio hicieron uso de estas medicinas con regularidad. Conclusiones Los datos de este estudio sugieren nuevas formas de pensar acerca de la asistencia farmacéutica, desde un punto de vista práctico y sistémico, y no sólo como la compra y distribución de medicamentos.(AU)

Mechanisms involved in anti-aging effects of guarana (Paullinia cupana) in Caenorhabditis elegans

Guarana (Paullinia cupana) is habitually ingested by people in the Amazon region and is a key ingredient in various energy drinks consumed worldwide. Extension in longevity and low prevalence of chronic age-related diseases have been associated to habitual intake of guarana. Anti-aging potential of guarana was also demonstrated in Caenorhabditis elegans; however, the mechanisms involved in its effects are not clear. Herein, we investigated the putative pathways that regulate the effects of guarana ethanolic extract (GEE) on lifespan using C. elegans. The major known longevity pathways were analyzed through mutant worms and RT-qPCR assay (DAF-2, DAF-16, SKN-1, SIR-2.1, HSF-1). The possible involvement of purinergic signaling was also investigated. This study demonstrated that GEE acts through antioxidant activity, DAF-16, HSF-1, and SKN-1 pathways, and human adenosine receptor ortholog (ADOR-1) to extend lifespan. GEE also downregulated skn-1, daf-16, sir-2.1 and hsp-16.2 in 9-day-old C. elegans, which might reflect less need to activate these protective genes due to direct antioxidant effects. Our results contribute to the comprehension of guarana effects in vivo, which might be helpful to prevent or treat aging-associated disorders, and also suggest purinergic signaling as a plausible therapeutic target for longevity studies.

Efeitos da carga anticolinérgica cognitiva em idosos ­ uma revisão integrativa / Effect of anticholinergic cognitive burden in the elderly ­ an integrative review

Idosos são mais susceptíveis aos efeitos adversos cognitivos de fármacos com atividade anticolinérgica. Isso se deve a fatores associados à velhice, como comprometimento da atividade colinérgica central, aumento da permeabilidade da barreira hematoencefálica, redução do metabolismo hepático e da excreção renal e polifarmácia. A escala de Carga Anticolinérgica Cognitiva (ACB) foi elaborada com o intuito de reduzir a ocorrência eventos adversos cognitivos à farmacoterapia, como declínio cognitivo, demência e delírio. O objetivo desta revisão integrativa foi reunir achados obtidos em estudos clínicos sobre a associação entre alterações cognitivas e ACB por meio da escala. A busca nas bases MEDLINE/PubMed e BVS-Bireme gerou 11 artigos completos em inglês. Sete são longitudinais, três transversais e um observacional. Oito foram conduzidos nos Estados Unidos. Nove de 10 evidenciaram a relação entre ACB e déficit cognitivo. O MMSE foi o teste de avaliação cognitiva mais usado. As evidências mostram a importância da revisão da farmacoterapia de todo paciente com déficit cognitivo ou delírio. Deve-se evitar assumir que o declínio cognitivo é demência até as possíveis causas farmacológicas tenham sido descartadas. (AU)

Elderly people are more susceptible to cognitive adverse effects of medications with anticholinergic activity. This is due to factors associated with aging, such as decline in central cholinergic activity, increase in blood-brain barrier permeability, decline in hepatic and renal metabolism and polypharmacy. The Anticholinergic Cognitive Burden (ACB) scale was developed reduce the risk for developing adverse cognitive outcomes such as cognitive impairment, dementia and delirium. The purpose of this integrative review is to bring together findings from clinical studies on the association between cognitive impairment and ACB scale. The search in MEDLINE/PubMed and BVS-Medicine bases generated 11 full articles in English. Seven were longitudinal, three transversal and one observational. Eight of them were conducted in the United States. Nine of 10 showed the relationship between the ACB and cognitive impairment due to at least one moderate or severe anticholinergic medication or due to concomitant use of multiple medications. MMSE was the most commonly cognitive assessment. Evidence shows the importance of the review of pharmacotherapy of all patients with cognitive impairment or delirium. It is important not to assume that cognitive decline is dementia until pharmacologic causes have been excluded. (AU)

Selenocysteine modulates resistance to environmental stress and confers anti-aging effects in C. elegans

OBJECTIVE: The free radical theory of aging suggests that cellular oxidative damage caused by free radicals is a leading cause of aging. In the present study, we examined the effects of a well-known anti-oxidant amino acid derivative, selenocysteine, in response to environmental stress and aging using Caenorhabditis elegans as a model system. METHOD: The response to oxidative stress induced by H2O2 or ultraviolet irradiation was compared between the untreated control and selenocysteine-treated groups. The effect of selenocysteine on lifespan and fertility was then determined. To examine the effect of selenocysteine on muscle aging, we monitored the change in motility with aging in both the untreated control and selenocysteine-treated groups. RESULTS: Dietary supplementation with selenocysteine significantly increased resistance to oxidative stress. Survival after ultraviolet irradiation was also increased by supplementation with selenocysteine. Treatment with selenocysteine confers a longevity phenotype without an accompanying reduction in fertility, which is frequently observed in lifespan-extending interventions as a trade-off in C. elegans. In addition, the age-related decline in motility was significantly delayed by supplementation of selenocysteine. CONCLUSION: These findings suggest that dietary supplementation of selenocysteine can modulate response to stressors and lead to lifespan extension, thus supporting the free radical theory of aging.

Protein carbonyl content: a novel biomarker for aging in HIV/AIDS patients

Abstract Background: The major complications of “treated” Human Immunodeficiency Virus (HIV) infection are cardiovascular disease, malignancy, renal disease, liver disease, bone disease, and perhaps neurological complications, which are phenomena of the normal aging process occurring at an earlier age in the HIV-infected population. The present study is aimed to explore protein carbonyl content as a biomarker for detecting oxidative DNA damage induced ART toxicity and/or accelerated aging in HIV/AIDS patients. Objective: To investigate the potential of carbonyl content as a biomarker for detecting oxidative Deoxyribonucleic acid (DNA) damage induced Antiretroviral Theraphy (ART) toxicity and/or accelerated aging in HIV/AIDS patients. Methods: In this case–control study a total 600 subjects were included. All subjects were randomly selected and grouped as HIV-negative (control group) (n = 300), HIV-infected ART naive (n = 100), HIV-infected on first line ART (n = 100), and HIV-infected on second line ART (n = 100). Seronegative control subjects were age- and sex-matched with the ART naive patients and the two other groups. Carbonyl protein was determined by the method described in Levine et al. DNA damage marker 8-OH-dG was determined using 8-hydroxy-2-deoxy Guanosine StressXpress ELA Kit by StressMarq Biosciences. Results: Protein carbonyl content levels and oxidative DNA damage were significantly higher (p < 0.05) in HIV-infected patients on second line ART and HIV-infected patients on first line ART than ART naive patients and controls. In a linear regression analysis, increased protein carbonyl content was positively associated with increased DNA damage (OR: 0.356; 95% CI: 0.287–0.426) p < 0.05. Conclusions: Carbonyl content may has a role as a biomarker for detecting oxidative DNA damage induced ART toxicity and/or accelerated aging in HIV/AIDS patients. Larger studies are warranted to elucidate the role of carbonyl content as a biomarker for premature aging in HIV/AIDS patients.

Programa de gerenciamento de doenças crônicas em um plano de saúde, são paulo, brasil / Programa de gestión de enfermedades crónicas en un seguro salud en el estado de são paulo, brasil / Chronic disease management program in a health plan, são paulo, brazil

RESUMO Atualmente as doenças crônicas não transmissíveis são as principais causas de morte no mundo. Consideradas doenças multifatoriais, têm em comum fatores de riscos modificáveis tais como inatividade física, colesterol elevado, excesso de peso, tabagismo, consumo excessivo de bebidas alcoólicas e alimentação não saudável. Com o objetivo de verificar o impacto por um programa de Gerenciamento de Doenças Crônicas, após dois anos de acompanhamento, surgiu esta pesquisa. Trata-se de programa desenvolvido com um grupo de clientes de uma autogestão localizada no estado de São Paulo. É um estudo transversal realizado durante os anos de 2014-2015 com dados de prontuário eletrônico que foram comparados parâmetros clínicos e hábitos de vida de 1.509 indivíduos participantes de um programa de gerenciamento de doenças em dois momentos: na entrada ao programa e após dois anos de participação. Observaram-se resultados satisfatórios na melhora de parâmetros clínicos relacionados aos níveis pressóricos e à dosagem de glicemia em jejum, assim como diminuição do sedentarismo em indivíduos abaixo dos 60 anos.

RESUMEN Actualmente las enfermedades crónicas no transmisibles son las principales causas de muerte en todo el mundo. Consideradas enfermedades multifactoriales, tienen en común factores de riesgo modificables, tales como inactividad física, colesterol alto, sobrepeso, tabaco, exceso de alcohol y alimentación poco sana. Con el objetivo de averiguar el impacto por un programa de Gestión de Enfermedades Crónicas, tras dos años de acompañamiento, se hizo esta investigación. Se trata de un programa desarrollado con un grupo de clientes de una autogestión ubicada en el estado de São Paulo, Brasil. Es un estudio transversal realizado durante los años de 2014-2015 con datos de registros médicos electrónicos, comparándose los parámetros clínicos y hábitos de vida de 1.509 personas que participan en un programa de gestión de enfermedades en dos ocasiones: cuando entran en el programa y después de dos años de participación. Se observaron resultados satisfactorios en la mejora de los parámetros clínicos relacionados con los niveles de presión arterial y a la dosificación de glucemia en ayunas, así como la disminución de la inactividad física en personas con edad abajo de 60 años.

ABSTRACT Currently, non-transmissible chronic diseases are leading causes of death worldwide. Considered as multifactorial diseases, they have common modifiable risk factors such as physical inactivity, high cholesterol, overweight, smoking, excessive alcohol consumption, and unhealthy diets. Aiming at verifying the impact of theChronic Disease Management program, this study arose after two years of follow-up. This is a program developed with a group of customers in a self-management platform in the state of São Paulo. This was a cross-sectional study carried out during 2014 and 2015 with electronic medical record data through the comparison ofthe clinical and lifestyle parameters of 1,509 individuals participating in a disease management program in two moments: at the program'sentry and two years after participation. Satisfactory results in the improvement of clinical parameters related to blood pressure and blood glucose levels in fasting were observed as well as decreased physical inactivity in individuals under 60 years of age.

Polypharmacy and Polymorbidity in Older Adults in Brazil: a public health challenge / Polifarmácia e polimorbidade em idosos no Brasil: um desafio em saúde pública

ABSTRACT OBJECTIVE To analyze variations in the prevalence of chronic use of medicines by older adults in Brazil according to its possible association with the most prevalent chronic diseases and demographic and health factors, and to identify risk factors for polypharmacy. METHODS A study based on data from the National Survey on Access, Use and Promotion of Rational Use of Medicines (PNAUM), a cross-sectional, population-based survey with probability sampling in Brazilian urban areas. The independent variable was the number of chronic-use medicines taken by older adults, linked to eight chronic diseases investigated. The intervening variables were gender, age group, marital status, level of education, socioeconomic status, Brazilian region, body mass index, smoking, self-perceived health, hospitalization in the previous year and having health insurance, besides the investigated chronic diseases. A multivariable analysis identified risk factors for polypharmacy. RESULTS Prevalence of at least one chronic-use medicines among older adults was 93.0%. Of the total number of older adults, 18.0% used at least five medications (polypharmacy). Polypharmacy was higher among the oldest individuals (20.0%), in the South region (25.0%), in those with poor self-perceived health (35.0%), in obese individuals (26.0%), in those with reported health insurance (23.0%) or hospitalization in the previous year (31.0%), and among those who reported any of the investigated diseases, particularly diabetes (36.0%) and heart diseases (43.0%). The variables remaining in the final risk model for polypharmacy were age, region, perceived health, health insurance, hospitalization in the previous year and all investigated diseases except stroke. CONCLUSIONS Older adults with specific diseases have risk factors for polypharmacy modifiable by actions aimed at the rational use of medicines. With the current population aging and successful drug access policy, the trend is an increase in drug use by older adults, which should feature as a priority in the planning agenda of the Brazilian Unified Health System (SUS).

RESUMO OBJETIVO Analisar as variações da prevalência do uso crônico de medicamentos por idosos no Brasil segundo sua possível associação com as doenças crônicas mais prevalentes, fatores sociodemográficos e de saúde, e identificar fatores de risco para polifarmácia. MÉTODOS Estudo com dados da Pesquisa Nacional de Acesso, Utilização e Promoção do Uso Racional de Medicamentos, de caráter transversal e amostra probabilística populacional em municípios brasileiros urbanos. A variável independente foi o número de medicamentos de uso crônico por idosos, vinculados às oito doenças crônicas investigadas. As variáveis intervenientes foram sexo, faixa etária, situação conjugal, escolaridade, nível socioeconômico, região do País, índice de massa corporal, hábito de fumar, percepção da própria saúde, internação no último ano e posse de plano de saúde privado, além das doenças crônicas referidas. Uma análise multivariável identificou os fatores de risco para polifarmácia. RESULTADOS A prevalência de pelo menos um medicamento de uso crônico entre idosos foi de 93,0%. Do total de idosos, 18,0% utilizavam pelo menos cinco medicamentos (polifarmácia). A polifarmácia foi maior entre os mais idosos (20,0%), na região Sul (25,0%), nos que avaliaram a própria saúde como ruim (35,0%), nos obesos (26,0%), nos que referiram ter plano de saúde (23,0%) ou internação no último ano (31,0%) e entre os que referiram qualquer uma das doenças investigadas, particularmente diabetes (36,0%) e doenças cardíacas (43,0%). No modelo final de risco para polifarmácia permaneceram idade, região, percepção de saúde, posse de plano de saúde, internação no último ano e todas as doenças investigadas exceto acidente vascular cerebral. CONCLUSÕES Idosos com doenças específicas têm fatores de risco para polifarmácia modificáveis por ações que visem o uso racional de medicamentos. Com o envelhecimento populacional em curso e a política exitosa de acesso a medicamentos, a tendência é aumentar a utilização de medicamentos por idosos, que deve ser prioridade na agenda de planejamento do Sistema Único de Saúde.

Effects of Er-Miao-San extracts on TNF-alpha-indueed MMP-1 expression in human dermal fibroblasts

BACKGROUND: Various health benefits have been attributed to Er-Miao-San (EMS), a traditional Chinese herbal formulation that contains equal amounts of cortex phellodendri (Phellodendron amurense Ruprecht) and rhizoma atractylodis (Atractylodes lancea D.C). However, its effect on the anti-inflammatory activity in human dermal fibroblasts (HDFs) and the mechanism underlying this effect are unknown. RESULTS: This study investigated the effects of EMS on TNF-α-induced MMP-1 expression in HDFs. Our data show that EMS inhibited TNF-α-induced MMP-1 expression in a concentration-dependent manner. Interestingly, EMS maintained IkB content without inhibiting the phosphorylation of MAPKs, which are well-established upstream kinases of NF-kB. Moreover, EMS reduced the level of nuclear p65 protein in HDFs. Luciferase assay revealed that EMS inhibits the transcriptional activity of NF-kBbystabilizing IkB. Our results show that EMS exerts its anti-inflammatory effect by inhibiting NF-kB-regulated genes such as IL-1ß and IL-8. Moreover, EMS effectively inhibited TNF-α-induced expression of MMP-1 via the NF-kBpathway. CONCLUSIONS: Taken together, our data suggest that EMS could potentially be used as an anti-inflammatory and anti-aging treatment.

Arctiin blocks hydrogen peroxide-induced senescence and cell death though microRNA expression changes in human dermal papilla cells

BACKGROUND: Accumulating evidence indicates that reactive oxygen species (ROS) are an important etiological factor for the induction of dermal papilla cell senescence and hair loss, which is also known alopecia. Arctiin is an active lignin isolated from Arctium lappa and has anti-inflammation, anti-microbial, and anti-carcinogenic effects. In the present study, we found that arctiin exerts anti-oxidative effects on human hair dermal papilla cells (HHDPCs). RESULTS: To better understand the mechanism, we analyzed the level of hydrogen peroxide (H2O2)-induced cytotoxicity, cell death, ROS production and senescence after arctiin pretreatment of HHDPCs. The results showed that arctiin pretreatment significantly inhibited the H2O2-induced reduction in cell viability. Moreover, H2O2-induced sub-G1 phase accumulation and G2 cell cycle arrest were also downregulated by arctiin pretreatment. Interestingly, the increase in intracellular ROS mediated by H2O2 was drastically decreased in HHDPCs cultured in the presence of arctiin. This effect was confirmed by senescence associated-beta galactosidase (SA-ß-gal) assay results; we found that arctiin pretreatment impaired H2O2-induced senescence in HHDPCs. Using microRNA (miRNA) microarray and bioinformatic analysis, we showed that this anti-oxidative effect of arctiin in HHDPCs was related with mitogen-activated protein kinase (MAPK) and Wnt signaling pathways. CONCLUSIONS: Taken together, our data suggest that arctiin has a protective effect on ROS-induced cell dysfunction in HHDPCs and may therefore be useful for alopecia prevention and treatment strategies.

Kinetin inhibits apoptosis of aging spleen cells induced by D-galactose in rats

Kinetin (Kn) is a cytokinin growth factor that exerts several anti-aging and antioxidant effects on cells and organs. To investigate the mechanism underlying apoptotic events in aging cells induced by D-galactose (D-gal), we examined the effect of Kn delivered via nuchal subcutaneous injection on D-gal-induced aging and apoptosis in rats. Our results showed that interleukin (IL)-2 levels and mitochondrial membrane potential (DeltaPsim) were decreased by Kn in aging rats while IL-6 production and apoptosis increased. In addition, the expression of anti-apoptotic Bcl-2 was low while that of Bax was high in the aging group. After treated with Kn, compared with aging group, there showed obvious difference in Kn group with elevated IL-2, proliferation index, Bcl-2, DeltaPsim and decreased IL-6 and Bax in splenic lymphocyte. Based on these results, we concluded that Kn can effectively protect the rat spleen from aging, apoptosis, and atrophy.

Antiaging, antistress and ROS scavenging activity of crude extract of Ocimum sanctum (L.) in Caenorhabditis elegans (Maupas, 1900).

Since aging is the most important risk factor for variety of diseases, the discovery of a wide range of chemical modulators of aging in model organisms encourages new strategies for targeting age associated diseases. Simple genetic manipulation leads to long-lived and healthy animals, so any compound which could have similar effect would prove a boon to mankind. In the present study, effect of different pharmacological doses (1.0, 0.1, 0.01 and 0.001 mg/mL) of O. sanctum crude extract were used to determine their impact on life span, thermotolerance and ROS scavenging activities in C. elegans. The results revealed that 1 mg/mL of O. sanctum extract significantly extended the life span of C. elegans. The extract also proved to be a strong free radical scavenger and increased resistance against thermal stress. It is also suggested that the protective and life span extending action of the crude extract is not only due to its antioxidant capacity but may also be mediated by modulation of some signaling pathways. Thus, in addition to all the known medicinal property of Ocimum, it is capable of increasing stress tolerance and life span in C. elegans.

Minocycline, but not ascorbic acid, increases motor activity and extends the life span of Drosophila melanogaster / La minociclina, pero no el ácido ascórbico, incrementa la actividad motora y extiende el período de vida de Drosophila melanogaster

In the present study we compared the effects of minocycline and ascorbic acid in the life span, motor activity and lipid peroxidation of Drosophila melanogaster, in an effort to find a substance capable of providing protection against oxidative stress in aging. In the flies treated with minocycline a very significant increase in the life span (101 ± 1.33 days) was observed when compared to those treated with ascorbic acid and controls (42.3% and 38.4%, respectively). The motor activity of minocycline treated flies also increased significantly with respect to control and ascorbic acid fed flies, from the 3rd to the 9th week of treatment. With regard to lipid peroxidation, it was found that the levels of malondialdehyde (MDA) in flies treated with minocycline showed no statistical differences to the control on the first day of treatment, but a significantly lower content on the day of 50% survival. In contrast, in flies treated with ascorbic acid significantly elevated levels of MDA compared to control and minocycline treated flies were detected throughout. These results suggest a protective effect of minocycline against oxidative stress and aging in D. melanogaster. An inhibitory effect on reactive oxygen species production may be an important contributing factor.

En el presente estudio se compararon los efectos del ácido ascórbico y la minociclina en la duración del periodo de vida, la actividad motora y la peroxidación lipídica de Drosophila melanogaster en un esfuerzo por encontrar una sustancia capaz de proporcionar protección contra el estrés oxidativo en el envejecimiento. En las moscas tratadas con minociclina se observó un aumento significativo en la duración de la vida (101 ± 1,33 días) en comparación con los tratados con ácido ascórbico y los controles (42,3% y 38,4%, respectivamente). La actividad motora de las moscas tratadas con minociclina aumentó significativamente cuando se comparó con las tratadas con ácido ascórbico y el control, desde la 3ra hasta la 9na semana de tratamiento. Con respecto a la peroxidación lipídica, se encontró que los niveles de malondialdehído (MDA) en moscas tratadas con minociclina no mostraron diferencias estadísticas con relación al control en el primer día de tratamiento; sin embargo, se detecto una disminución significativa de la concentración de MDA cuando se alcanzó el 50% de sobrevida. En contraste, en moscas tratadas con ácido ascórbico observamos que los niveles de MDA estaban significativamente elevados, cuando se compararon con las moscas tratadas con minociclina y el control a lo largo de todo el tratamiento. Estos resultados sugieren un efecto protector de la minociclina frente al estrés oxidativo y el envejecimiento en D. melanogaster, aunque un efecto inhibidor sobre la producción de especies reactivas del oxígeno puede ser un factor contribuyente importante.

Electrolyzed-reduced water increases resistance to oxidative stress, fertility, and lifespan via insulin/IGF-1-like signal in C. elegans

Electrolyzed-reduced water (ERW) scavenges reactive oxygen species and is a powerful anti-oxidant. A positive correlation between oxidative stress and aging has been proved in many model organisms. In Caenorhabditis elegans, many long-lived mutants showed reduced fertility as a trade off against longevity phenotype. We aimed to study the effect of ERW on oxidative stress, fertility and lifespan of C. elegans. We also investigated the genetic pathway involved in the effect of ERW on resistance to oxidative stress and lifespan. We compared lifespan and fertility of worms in media prepared with distilled water and ERW. ERW significantly extended lifespan and increased the number of progeny produced. Then the effect of ERW on resistance to oxidative stress and lifespan of long-lived mutants was determined. ERW increased resistance to oxidative stress and lifespan of eat-2, a genetic model of dietary restriction, but had no effect on those of age-1, which is involved in insulin/insulin-like growth factor (IGF)-1-like signal. In addition, knockdown of daf-16, the downstream mediator of insulin/IGF-1-like signal, completely prevented the effect of ERW on lifespan. These findings suggest that ERW can extend lifespan without accompanying reduced fertility and modulate resistance to oxidative stress and lifespan via insulin/IGF-1-like signal in C. elegans.

Bioplastia na lipodistrofia de pacientes com HIV/AIDS / Bioplasty for lipodystrophy in patients with HIV/AIDS

INTRODUÇÃO: O início do tratamento da síndrome da imunodeficiência adquirida (AIDS) com a terapia antirretroviral de alta atividade (HAART), na década de 1990, aumentou, consideravelmente, a longevidade e a qualidade de vida dos portadores da doença. A redução da morbidade e da mortalidade associadas a doenças infecciosas e neoplásicas oportunistas, porém, tem sido acompanhada pelo aumento da prevalência de outras doenças, entre elas a lipodistrofia associada ao vírus da imunodeficiência humana (HIV). A lipodistrofia decorre da toxicidade de drogas utilizadas na terapia antirretroviral, sendo atribuída aos inibidores de protease e aos inibidores da transcriptase reversa análogos do nucleosídeo. Este trabalho aborda a lipoatrofia facial, que confere um aspecto de envelhecimento precoce e traz de volta o velho estigma da "facies da AIDS", podendo impactar negativamente na qualidade de vida dos portadores de HIV. MÉTODO: Neste estudo foram incluídos 41 pacientes apresentando lipoatrofia facial, que foram submetidos a preenchimento com polimetilmetacrilato (PMMA) no Hospital Universitário da Universidade Federal de Juiz de Fora (HU-UFJF) e na clínica Plastic Center, Clínica de Cirurgia Plástica em Juiz de Fora, no período entre janeiro de 2010 e fevereiro de 2012. RESULTADOS: O número de procedimentos realizados em cada paciente variou de 1 a 4, sendo respeitado um intervalo mínimo de 90 dias entre eles. A quantidade de PMMA utilizado variou de acordo com o grau e a região a serem corrigidos, ficando entre 3 ml e 18 ml por procedimento. Em todos os pacientes, o resultado obtido foi favorável esteticamente. CONCLUSÕES: Os resultados obtidos pela bioplastia com PMMA foram considerados satisfatórios pelos pacientes. O material utilizado possui alta adaptabilidade às áreas receptoras, necessitando apenas da modelagem e da quantidade adequada para que apresente bom padrão estético.

BACKGROUND: When the treatment of acquired immunodeficiency syndrome (AIDS) with highly active antiretroviral therapy (HAART) began in the 1990s, it considerably increased the life expectancy and quality of life of AIDS patients. However, the decrease in morbidity and mortality associated with opportunistic infectious and neoplastic diseases was accompanied by an increase in the prevalence of other diseases, including HIV-associated lipodystrophy. Lipodystrophy is due to the toxicity of drugs used in antiretroviral therapy, including protease inhibitors and nucleoside analog reverse transcriptase inhibitors. This article discusses the treatment of facial lipodystrophy, which confers an appearance of premature aging and brings back the old stigma of the "AIDS face," which negatively impacts the quality of life of HIV carriers. METHODS: Forty-one patients with facial lipoatrophy received filling with polymethylmethacrylate (PMMA) at the Hospital Universitário da Universidade Federal de Juiz de Fora (HU-UFJF) and at the Plastic Center Clinic, Plastic Surgery Clinic in Juiz de Fora between January 2010 and February 2012. RESULTS: Patients received 1 to 4 procedures with a minimum interval of 90 days between procedures. The amount of PMMA used ranged from 3 to 18 mL per procedure according to the degree and region to be corrected. The results were aesthetically favorable in all patients. CONCLUSIONS: The results obtained through bioplasty with PMMA are considered satisfactory by patients. The material used is highly adaptable to the receiving areas, requiring only modeling and an adequate amount in order to obtain good aesthetic results.

[Studying the anti-aging effect of human growth hormone on human fibroblast cells via telomerase activity]

In recent years, studies have focused on the telomerase for cancer treatment by repressing telomerase in cancerous cells or prevent cell aging by activating it in the aged cells. Thus, in these studies natural and synthetic agents have been used to repress or activate telomerase. In this research, we investigated the effects of human growth hormone [hGH] on aging via evaluation of telomerase activity. Primary human foreskin fibroblast cells were isolated, cultured and treated with different concentrations of hGH. BrdU and MTT cell proliferation assays and cells number counting. Cell aging was assayed by the senescence sensitive galactosidase staining method. Telomerase activity was measured with a telomerase PCR ELISA kit.Data were analyzed with SPSS software [one-way ANOVA and univariate ANOVA]. Our results indicated that cells treated with a lower concentration [0.1, 1 ng/ml] of hGH had more green color cells [aged cells]. Furthermore, cell proliferation increased with increasing hGH concentrations [10 to 100 ng/ml] which was significant in comparison with untreated control cells. TRAP assay results indicated that telomerase activity increased with increasing hGH concentration, but there was no significant difference. Additionally, more rapid cell growth and telomerase activity was noted in the absence of H2 O2 when compared with the presence of H2 O2, which was significantly different. Although increasing cell proliferation along with increasing hGH concentration was confirmed by all cell proliferation assays, only the cell counting test was statistically significant. Thus, it is inconclusive that hGH [up to 100 ng/ml] has an anti-aging effect. Also, because there was no significant difference in the telomerase activity results [in spite of increasing progress along with increasing hGH concentration] we can not certainly conclude that hGH [up to 100 ng/ml] impacts telomerase activity

Effect of Emblica officinalis (Gaertn) on lens regeneration in the frog, Rana cyanophlyctis (Schneider).

Emblica officinalis (Amla) accelerated cell proliferation and dedifferentiation of pigmented epithelial cells of dorsal iris and consequently induced lens regeneration in R. cyanophlyctis. Further it enhanced the percentage of lens regeneration not only in young tadpoles but also is adult frogs. Lens regeneration ability declined with the age of animals in both control as well as treated groups.

Effects of delta-tocotrienol and polyphenol on ageing induced oxidative stress and inflammation in humans

To evaluate the synergistic effects of delta-tocotrienol and polyphenols on ageing induced oxidative stress and inflammation on healthy elderly humans. It was a randomized double blinded control trial. Total 69 healthy volunteers aged 50-78 years consisting of 47 male and 22 female were included after informed consent. All the subjects were screened at baseline and randomly grouped in A and B. Nutritional supplement [delta-tocotrienol 200mg, Quercetin 300 mg, Resveratrol 100mg] and placebo [Sucrose] were given to groups A and B subjects respectively for 4 weeks. Then subjects of two groups were crossed over for next 4 weeks. Serum total antioxidant status [TAS] and Gamma glutamyl transferase [GGT] were analyzed by using Randox kits [UK] on automatic Chemistry analyzer Selectra E. Estimation of serum Nitrate was done on ELISA by using Kit [Cayman, UK]. Serum hS-C-recative protein [CRP] was analyzed by using chemiluminescent immunometric assay kit on Immulite 1000. There was significant reduction in pre versus post median [IQR] levels in serum GGT 26 [21-34] vs 21 [19-25] U/L after nutritional supplement [p=0<0.01]. Serum CRP and Nitrate levels were also significantly decreased from 2.1[1.1-3.1] and 8.30[3.52-16.20] to 1.4[0.75-2.3] mg/L and 7.65[3.74-11.58] micro mol/L respectively [p=0<0.01]. TAS was improved from 1.45 [1.33-1.62] to 1.61 [1.46-1.70] mmol/L with nutritional supplement [p=0<0.01]. The study has demonstrated that combination of tocotrienol and polyphenol delays the ageing process by reducing the deteriorating effects of oxidative stress and inflammation