Fight Aging! Newsletter, August 26th 2019

Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe or unsubscribe from the newsletter, please visit: https://www.fightaging.org/newsletter/ Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out more: https://www.fightaging.org/services/ Contents Healthy Aging is a Harmful Concept that will Misdirect Research Efforts Popular Science Publications Struggle to Grasp the State of Aging Research World Health Organization Staff Continue their Efforts to be Irrelevant in the Matter of Human Aging Forever Healthy Foundation Begins Publishing Risk/Benefit Analyses of Potential Treatments for Aging mTOR Inhibition via Rapamycin and the Concept of Beneficial Diabetes Regular Exercise Slows Cognitive Decline and Age-Related Damage to the Brain The Genetics of Human Longevity in a Nutshell: Only a Few Identified Variants, and Everything Else a Mystery Juvenescence Raises a Further 100M to Invest in Therapies to Treat Aging Amyloid-β Causes Blood-Brain Barrier Leakage A Fast Review of the Present Consensus on Mechanisms Deter...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs

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Macrophages are important in mounting an innate immune response to injury as well as in repair of injury. Gene expression of Rho proteins is known to be increased in fibrotic models; however, the role of these proteins in idiopathic pulmonary fibrosis (IPF) is not known. Here, we show that BAL cells from patients with IPF have a profibrotic phenotype secondary to increased activation of the small GTPase Rac1. Rac1 activation requires a posttranslational modification, geranylgeranylation, of the C-terminal cysteine residue. We found that by supplying more substrate for geranylgeranylation, Rac1 activation was substantially ...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
We hypothesized that the store-operated calcium entry (SOCE) channel, Orai1, participates in the activation of Th17 cells and influences renal injury. In rats, following renal ischemia/reperfusion (I/R), there was a rapid and sustained influx of Orai1+ CD4 T cells and IL-17 expression was restricted to Orai1+ cells. When kidney CD4+ cells of post–acute kidney injury (post-AKI) rats were stimulated with angiotensin II and elevated Na+ (10–7 M/170 mM) in vitro, there was an enhanced response in intracellular Ca2+ and IL-17 expression, which was blocked by SOCE inhibitors 2APB, YM58483/BTP2, or AnCoA4. In vivo, YM...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
The interleukin 3 receptor (CD123) is a transmembrane protein that is absent or hardly expressed on normal hematopoietic stem cells, but highly expressed on the surface of cancer cells in several hematologic malignancies. In this issue of the JCI, Togami et al. investigated the mechanism of resistance to the recently approved anti-CD123 agent tagraxofusp, which consists of interleukin 3 fused to a truncated diphtheria toxin (DT) molecule. The authors demonstrated that loss of the intracellular target for DT, diphthamide, a conservative modification of histidine 715 in eukaryotic elongation factor 2, resulted in tagraxofusp...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
T cell autoreactivity is a hallmark of autoimmune diseases but can also benefit self-maintenance and foster tissue repair. Here, we investigated whether heart-specific T cells exert salutary or detrimental effects in the context of myocardial infarction (MI), the leading cause of death worldwide. After screening more than 150 class II–restricted epitopes, we found that myosin heavy chain α (MYHCA) was a dominant cardiac antigen triggering post-MI CD4+ T cell activation in Balb/c mice. Transferred MYHCA614–629-specific CD4+ T cells (TCR-M cells) selectively accumulated in the myocardium and mediastinal lym...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Cardiac tissue necrosis secondary to coronary artery occlusion is one of the most common and deadly sterile injuries in developed countries. In this issue of the JCI, Rieckmann et al. identified and characterized antigen-specific CD4+ T helper (Th) cells that developed in the context of myocardial infarction (MI) in mice. They showed that myosin heavy chain α (MYHCA) is a dominant cardiac autoantigen and that T cells with T cell receptor (TCR) specificity to MYHCA acquired a Treg phenotype when adoptively transferred into infarcted mice, which mediated a cardioprotective healing response. Thus, Rieckmann et al. showe...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Tumor-resident lymphocytes can mount a response against neoantigens expressed in microsatellite-stable gastrointestinal (GI) cancers, and adoptive transfer of neoantigen-specific lymphocytes has demonstrated antitumor activity in selected patients. However, whether peripheral blood could be used as an alternative minimally invasive source to identify lymphocytes targeting neoantigens in patients with GI cancer with relatively low mutation burden is unclear. We used a personalized high-throughput screening strategy to investigate whether PD-1 expression in peripheral blood could be used to identify CD8+ or CD4+ lymphocytes ...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
RESUMO Objetivo: Avaliar poss íveis associações do risco nutricional com os desfechos clínicos desfavoráveis em pacientes críticos internados na unidade de terapia intensiva. Métodos: Estudo de coorte, prospectivo, realizado em 200 pacientes em unidade de terapia intensiva de hospital universitário. O risco nutricional foi avaliado pelos escores NRS-2002 e NUTRIC. Pacientes com escore ≥ 5 foram considerados de alto risco nutricional. Os dados e desfechos cl ínicos foram obtidos de registros clínicos dos pacientes. Utilizou-se análise de regress...
Source: Revista Brasileira de Terapia Intensiva - Category: Intensive Care Source Type: research
Conclusion: Septic patients with a past history of heart failure received 1L less IV fluids in the first 24 hours with no difference in mortality.
Source: Revista Brasileira de Terapia Intensiva - Category: Intensive Care Source Type: research
RESUMO A sepse persiste como importante sobrecarga à saúde pública nos Estados Unidos e em todo o mundo. Com o crescente uso de tecnologias laboratoriais, tem se renovado o interesse na utilização de biomarcadores na sepse, para auxiliar em um processo mais preciso e direcionado para tomadas de decisão. Os peptídeos natriuréticos vem sendo c ada vez mais reconhecidos por seu papel que vai além da insuficiência cardíaca. Estes peptídeos estão comumente elevados em pacientes críticos que apresentam condições de disf...
Source: Revista Brasileira de Terapia Intensiva - Category: Intensive Care Source Type: research
Conclusion: The NUTRIC score is related to clinical outcomes, such as length of hospital stay, and is appropriate for use in critically ill patients in intensive care units.
Source: Revista Brasileira de Terapia Intensiva - Category: Intensive Care Source Type: research
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