Fight Aging! Newsletter, April 8th 2019

This study did not confirm the hypothesis that ELL individuals have lower polygenic risk scores for cardiovascular-related phenotypes. Only the HDL cholesterol and triglyceride PRS were nominally significantly associated with ELL participants. In contrast and as expected, ELL individuals had higher polygenic risk scores for exceptional longevity (EL). In regards to the associations of the various cardiovascular PRS with EL, no findings survived correction for multiple testing. This is despite validating the utility of the lipid PRS by confirming positive associations with measured lipid levels in our sample. Interestingly, the different lipid PRS were based on GWAS that found a large number of genome-wide significant loci. ELL individuals had lower LDL and total cholesterol levels than controls in this study, but they did not differ on their respective PRS. This may suggest that environmental factors, perhaps lifestyle-related, influenced these lipid levels, which possibly promote longevity. In contrast, the UK Biobank study observed that extreme parental longevity (defined as at least one parent who survived to the top 1% of age at death) had lower polygenic risk for several cardiovascular health measures. Namely coronary artery disease, systolic blood pressure, body mass index, high-density lipoproteins, low-density lipoproteins, and triglycerides. A similar result for HDL cholesterol and extreme parental longevity (EPL) by the UK Biobank to the current study was rep...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs

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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
The objective of this work was to study the behavior of physico-chemical variables and kinetic and biological responses in industrial cultivation of Spirulina sp. LEB 18, aiming at the operation of a microalgal photobiorefinery. The maximum specific growth rate (0.133 1/d), the minimum generation time (5.2 d) and maximum productivity (14.9 g/m ².d) were obtained in the first 9 d of microalgae growth. The maximum biomass concentration (1.64 g/L) was obtained in 37 d of cultivation. The highest levels of carbohydrates, proteins and lipids in the biomass were 10.6, 57.0 and 11.7%, respectively. The plant monitoring demon...
Source: Brazilian Journal of Chemical Engineering - Category: Chemistry Source Type: research
ABSTRACT In this research, sol-gel precipitation using CO2 impregnation and mechanical fragmentation method was applied to produce precipitated silica from Palm Oil Mill Fly Ash (POMFA). Carbon dioxide (CO2) was used in order to reduce the cost of the process and to enable sodium hydroxide recovery. The precipitation process was done in a stirred temperature-controlled baffled glass precipitator. The response surface method with the central composite design was applied to optimize the stirring speed and the CO2 flow rate. The pH and the temperature of the precipitation process were varied for tailoring the specific surface...
Source: Brazilian Journal of Chemical Engineering - Category: Chemistry Source Type: research
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