Fight Aging! Newsletter, June 4th 2018

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 Support for Longevity Science is the Most Effective Form of Philanthropy When I am Eighty-Five Do FOXA2-Related Changes in the Nuclear Lamina Contribute to Liver Aging? An Example of the Importance of Gut Microbiota to Aging in Flies Lower Levels of KIFC3 Observed in Aging are Involved in the Decline of Autophagy A Commentary on Senolytic Gene Therapies to Target p16 Overexpression Can Present Stem Cell Therapies Improve Vaccine Response in the Elderly? Discussing the Dog Aging Project with Matt Kaeberlein ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs

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AbstractLayered double hydroxides (LDHs) are 2D ionic lamellar nanomaterials, which attract increasing interest for applications in different fields. This paper shows that their morphology is strongly affected by the microstructure of the substrate on which they grow. Zn –Al LDHs were grown in the same conditions on Al substrates with different microstructural features obtained from cold-rolled sheets by annealing at 265 °C for increasing soaking time up to 1 h. LDH morphology was then investigated through scanning electron microscopy observations. The homogene ous distribution of petals on the substrat...
Source: European Journal of Applied Physiology - Category: Physiology Source Type: research
Tumorigenicity is a well-documented risk to overcome for pluripotent or multipotent cell applications in regenerative medicine. To address the emerging demand for safe cell sources in tissue regeneration, we established a novel, protein-based reprogramming method that does not require genome integration or oncogene activation to yield multipotent fibromodulin (FMOD)-reprogrammed (FReP) cells from dermal fibroblasts. When compared with induced pluripotent stem cells (iPSCs), FReP cells exhibited a superior capability for bone and skeletal muscle regeneration with markedly less tumorigenic risk. Moreover, we showed that the ...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Cytosolic arginine sensor for mTORC1 subunits 1 and 2 (CASTOR1 and CASTOR2) inhibit the mammalian target of rapamycin complex 1 (mTORC1) upon arginine deprivation. mTORC1 regulates cell proliferation, survival, and metabolism and is often dysregulated in cancers, indicating that cancer cells may regulate CASTOR1 and CASTOR2 to control mTORC1 signaling and promote tumorigenesis. mTORC1 is the most effective therapeutic target of Kaposi sarcoma, which is caused by infection with the Kaposi sarcoma–associated herpesvirus (KSHV). Hence, KSHV-induced cellular transformation is a suitable model for investigating mTORC1 reg...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
The presence of tumor-infiltrating T cells is associated with favorable patient outcomes, yet most pancreatic cancers are immunologically silent and resistant to currently available immunotherapies. Here we show using a syngeneic orthotopic implantation model of pancreatic cancer that Pik3ca regulates tumor immunogenicity. Genetic silencing of Pik3ca in KrasG12D/Trp53R172H-driven pancreatic tumors resulted in infiltration of T cells, complete tumor regression, and 100% survival of immunocompetent host mice. By contrast, Pik3ca-null tumors implanted in T cell–deficient mice progressed and killed all of the animals. Ad...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Glycosylation of immune receptors and ligands, such as T cell receptor and coinhibitory molecules, regulates immune signaling activation and immune surveillance. However, how oncogenic signaling initiates glycosylation of coinhibitory molecules to induce immunosuppression remains unclear. Here we show that IL-6–activated JAK1 phosphorylates programmed death-ligand 1 (PD-L1) Tyr112, which recruits the endoplasmic reticulum–associated N-glycosyltransferase STT3A to catalyze PD-L1 glycosylation and maintain PD-L1 stability. Targeting of IL-6 by IL-6 antibody induced synergistic T cell killing effects when combined...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Programmed death-1 receptor ligand 1 (PD-L1) is a promising therapeutic target in aggressive cancers. However, immune landscapes and cancer hallmarks of human PD-L1+ tumors as well as their roles in determining therapeutic efficacies are unknown. Here, we showed, in detailed studies of gene data regarding 9769 patients of 32 types of human cancers, that PD-L1 could not exclusively represent the IFN-γ signature and potentially signified proinflammatory myeloid responses in a tumor. PD-L1 heterogeneity endowed by local immune landscapes controlled cancer hallmarks and clinical outcomes of patients. Mechanically, NF-&ka...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
The gut microbiome is a key regulator of bone health that affects postnatal skeletal development and skeletal involution. Alterations in microbiota composition and host responses to the microbiota contribute to pathological bone loss, while changes in microbiota composition that prevent, or reverse, bone loss may be achieved by nutritional supplements with prebiotics and probiotics. One mechanism whereby microbes influence organs of the body is through the production of metabolites that diffuse from the gut into the systemic circulation. Recently, short-chain fatty acids (SCFAs), which are generated by fermentation of comp...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
The migration of leukocytes into the CNS drives the neuropathology of multiple sclerosis (MS). It is likely that this penetration utilizes energy resources that remain to be defined. Using the experimental autoimmune encephalomyelitis (EAE) model of MS, we determined that macrophages within the perivascular cuff of postcapillary venules are highly glycolytic, as manifested by strong expression of lactate dehydrogenase A (LDHA), which converts pyruvate to lactate. These macrophages expressed prominent levels of monocarboxylate transporter-4 (MCT-4), which is specialized in the secretion of lactate from glycolytic cells. The...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Publication date: Available online 14 July 2019Source: Colloids and Surfaces A: Physicochemical and Engineering AspectsAuthor(s): Ying Wang, Jingwen Chen, Qianqian Han, Qiang Luo, Hongmei Zhang, Yanqing WangAbstractLentinan(LNT) has many kinds of pharmacological activities such as antioxidative activities, hypoglycemic effect, anti-hyperlipidemic effect and so on. Here, LNT was used as the skeleton material to couple with doxorubicin(DOX) by forming the LNT–DOX conjugates in order to enhance anticancer effects and reduce the systemic side effects of DOX. Based on the screening results, we observed that LNT can acted ...
Source: Colloids and Surfaces A: Physicochemical and Engineering Aspects - Category: Chemistry Source Type: research
Publication date: Available online 14 July 2019Source: Colloids and Surfaces A: Physicochemical and Engineering AspectsAuthor(s): Pablo Tancredi, Lionel S. Veiga, Octavio Garate, Gabriel YbarraAbstractIron oxide nanoparticles were synthesized by the co-precipitation method and subjected to an adsorption and functionalization process at controlled pH with five different small carboxylate ligands, namely: citrate, tartrate, gluconate, succinate and β-alanine. The efficiency of the functionalization was evaluated by infrared spectroscopy and thermogravimetric measurements, finding that the presence of hydroxyl groups in ...
Source: Colloids and Surfaces A: Physicochemical and Engineering Aspects - Category: Chemistry Source Type: research
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