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.

MicroRNA expression signatures in lungs of mice infected with Mycobacterium tuberculosis.

Tuberculosis (TB) is a major public health concern worldwide; however the factors that account for resistance or susceptibility to disease are not completely understood. Although some studies suggest that the differential expression of miRNAs in peripheral blood of TB patients could be useful as biomarkers of active disease, their involvement during the inflammatory process in lungs of infected individuals is unknown. Here, we evaluated the global expression of miRNAs in the lungs of mice experimentally infected with Mycobacterium tuberculosis on 30 and 60 days post-infection. We observed that several miRNAs were differentially expressed compared to uninfected mice. Furthermore, we verified that the expression of miR-135b, miR-21, miR-155, miR-146a, and miR-146b was significantly altered in distinct leukocyte subsets isolated from lungs of infected mice, while genes potentially targeted by those miRNAs were associated with a diversity of immune related molecular pathways. Importantly, we validated the inhibition of Pellino 1 expression by miR-135b in vitro. Overall, this study contributes to the understanding of the dynamics of miRNA expression in lungs during experimental TB and adds further perspectives into the role of miRNAs on the regulation of immune processes such as leukocyte activation.

Low-dose plasmid DNA treatment increases plasma vasopressin and regulates blood pressure in experimental endotoxemia.

BACKGROUND: Although plasmid DNA encoding an antigen from pathogens or tumor cells has been widely studied as vaccine, the use of plasmid vector (without insert) as therapeutic agent requires further investigation. RESULTS: Here, we showed that plasmid DNA (pcDNA3) at low doses inhibits the production of IL-6 and TNF-α by lipopolysaccharide (LPS)-stimulated macrophage cell line J774. These findings led us to evaluate whether plasmid DNA could act as an anti-inflammatory agent in a Wistar rat endotoxemia model. Rats injected simultaneously with 1.5 mg/kg of LPS and 10 or 20 µg of plasmid DNA had a remarkable attenuation of mean arterial blood pressure (MAP) drop at 2 hours after treatment when compared with rats injected with LPS only. The beneficial effect of the plasmid DNA on MAP was associated with decreased expression of IL-6 in liver and increased concentration of plasma vasopressin (AVP), a known vasoconstrictor that has been investigated in hemorrhagic shock management. No difference was observed in relation to nitric oxide (NO) production. CONCLUSION: Our results demonstrate for the first time that plasmid DNA vector at low doses presents anti-inflammatory property and constitutes a novel approach with therapeutic potential in inflammatory diseases.