Fight Aging! Newsletter, September 25th 2017

Fight Aging! provides a weekly digest of news and commentary for thousands of subscribers interested in the latest longevity science: progress towards the medical control of aging in order to prevent age-related frailty, suffering, and disease, as well as improvements in the present understanding of what works and what doesn't work when it comes to extending healthy life. Expect to see summaries of recent advances in medical research, news from the scientific community, advocacy and fundraising initiatives to help speed work on the repair and reversal of aging, links to online resources, and much more. This content is published under the Creative Commons Attribution 4.0 International License. You are encouraged to republish and rewrite it in any way you see fit, the only requirements being that you provide attribution and a link to Fight Aging! To subscribe or unsubscribe please visit: https://www.fightaging.org/newsletter/ Contents HSP90 Inhibitors as Another New Class of Potential Senolytic Drug Compounds An Introduction to DAF-16 and FOXO in the Context of Aging and Longevity Evidence Accumulates for Macrophages to be Central to Exceptional Regeneration MicroRNA in Macrophage Exosomes Mediates Harms Done by Visceral Fat Tissue Wolf has been Cried So Very Many Times When it Comes to Anti-Aging Therapies The First Practical Means of Human Rejuvenation are Not Distant Reviewing the Effects of Exercise on Mitophagy and Mitochondrial Functi...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs

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Neutrophil extracellular traps (NETs) are involved in the pathogenesis of many infectious diseases, yet their dynamics and impact on HIV/SIV infection have not yet been assessed. We hypothesized that SIV infection and the related microbial translocation trigger NET activation and release (NETosis), and we investigated the interactions between NETs and immune cell populations and platelets. We compared and contrasted the levels of NETs between SIV-uninfected, SIV-infected, and SIV-infected antiretroviral-treated nonhuman primates. We also cocultured neutrophils from these animals with either peripheral blood mononuclear cel...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
SMAD4 is the only common SMAD in TGF-β signaling that usually impedes immune cell activation in the tumor microenvironment. However, we demonstrated here that selective deletion of Smad4 in NK cells actually led to dramatically reduced tumor cell rejection and augmented tumor cell metastases, reduced murine CMV clearance, as well as impeded NK cell homeostasis and maturation. This was associated with a downregulation of granzyme B (Gzmb), Kit, and Prdm1 in Smad4-deficient NK cells. We further unveiled the mechanism by which SMAD4 promotes Gzmb expression. Gzmb was identified as a direct target of a transcriptional com...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Dysregulated intestinal epithelial apoptosis initiates gut injury, alters the intestinal barrier, and can facilitate bacterial translocation leading to a systemic inflammatory response syndrome (SIRS) and/or multi-organ dysfunction syndrome (MODS). A variety of gastrointestinal disorders, including inflammatory bowel disease, have been linked to intestinal apoptosis. Similarly, intestinal hyperpermeability and gut failure occur in critically ill patients, putting the gut at the center of SIRS pathology. Regulation of apoptosis and immune-modulatory functions have been ascribed to Thirty-eight-negative kinase 1 (TNK1), whos...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
The stroma of solid tumors can exclude or limit immune infiltration, or lead to the recruitment of tumor-promoting rather than tumor-attacking immune cells. This finding was reported by Jayaprakash et al. in this issue of the JCI, and it was particularly prominent in the hypoxic zones of tumors in the transgenic adenocarcinoma of the mouse prostate (TRAMP) cancer models. A current clinical goal of immune checkpoint blockade (ICB) is to extend its utility to more patients by converting immunologically “cold” tumors that do not provoke a strong immunological response to “hot” tumors that are invaded b...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
In critically ill patients, disruption of intestinal epithelial cell function occurs due to exposure of the epithelium to toxic internal and external inflammatory stimuli, which are key factors that trigger sepsis and multi-organ dysfunction syndrome (MODS). A greater understanding of how trauma and gut failure lead to sepsis and progression to MODS is much needed. In this issue of the JCI, Armacki and colleagues identify mechanisms by which thirty-eight-negative kinase 1 (TNK1) promotes the progression from intestinal apoptosis and gut failure to bacterial translocation, sepsis, and MODS. Moreover, the results of this stu...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Despite the success of immune checkpoint blockade against melanoma, many “cold” tumors like prostate cancer remain unresponsive. We found that hypoxic zones were prevalent across preclinical prostate cancer and resisted T cell infiltration even in the context of CTLA-4 and PD-1 blockade. We demonstrated that the hypoxia-activated prodrug TH-302 reduces or eliminates hypoxia in these tumors. Combination therapy with this hypoxia-prodrug and checkpoint blockade cooperated to cure more than 80% of tumors in the transgenic adenocarcinoma of the mouse prostate–derived (TRAMP-derived) TRAMP-C2 model. Immunofluo...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Enterovirus A71 (EV-A71) receptors that have been identified to date cannot fully explain the pathogenesis of EV-A71, which is an important global cause of hand, foot, and mouth disease and life-threatening encephalitis. We identified an IFN-γ–inducible EV-A71 cellular entry factor, human tryptophanyl-tRNA synthetase (hWARS), using genome-wide RNAi library screening. The importance of hWARS in mediating virus entry and infectivity was confirmed by virus attachment, in vitro pulldown, antibody/antigen blocking, and CRISPR/Cas9-mediated deletion. Hyperexpression and plasma membrane translocation of hWARS were obs...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
The paper, titled 'Debt or Death?', used data on 9.5 million nationally-representative patients between 1998 and 2014, who spend an average of $92,098 a year trying to stay alive.
Source: the Mail online | Health - Category: Consumer Health News Source Type: news
Adult scoliosis is different from the type children like Princess Eugenie develop - as Roger Neuberg, 77, from Leicester,experienced first-hand. This is his story.
Source: the Mail online | Health - Category: Consumer Health News Source Type: news
Source: Peerview CME/CE Video Podcast - Internal Medicine International - Category: Internal Medicine Authors: Tags: Science, Medicine Source Type: video
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