We do know that telomerase activators elongate telomeres but do we know if they impact life span of animal models? In her 2012 paper Blasco was saying:

Aramchol was non-mutagenic in vitro in the Ames test and chromosomal aberrations test, each of which is a test to determine whether the subject chemical can cause mutations in the DNA of an organism. In addition, in bone marrow micronucleus test in male rats at a 2000 mg/kg oral dose (the maximum recommended dose in accordance with ICH S2 (R1)), Aramchol was not clastogenic, meaning it did not give rise to or induce disruption or breakages of chromosomes, nor was it aneugenic, meaning it did not cause the number of chromosomes in the nucleus of a cell to not be an exact multiple of the monoploid number of a particular species.

The primary endpoint of the study was the change from baseline to end of study in liver triglycerides ratio as measured by magnetic resonance spectroscopy, or MRS (Aramchol 600mg vs. placebo). Secondary endpoints, demonstrated through biopsy, included fibrosis improvement by at least one stage or more without worsening of NASH (defined by an increase of inflammation and or ballooning) and NASH resolution (defined by ballooning score 0 and inflammation score 0-1 at termination) without worsening of fibrosis. Other secondary endpoints included improvement (2 points or more) in NASH activity index, as measured by NAS or SAF, without worsening fibrosis and change in baseline to week 52/termination in ALT (U/L).

In the annual general meeting to be convened in 2019, our Board plans to nominate Mr. Baharaff and Mr. Heinberg for re-election to serve as Class II Directors until the close of the annual general meeting to be held in 2022 and nominate Prof. Oren for re-election to serve as a Class III Director until the close of the annual general meeting to be held in 2020.

Capstone Therapeutics (NasdaqGM: CAPS ) Capstone Therapeutics (trade name of OrthoLogic Corp.) is a biotechnology company committed to developing a pipeline of novel therapeutic peptides aimed at helping patients with under-served medical conditions. The Company is focused on development and commercialization of two product platforms: AZX100 and Chrysalin® (rusalatide acetate or TP508). AZX100 is a novel synthetic 24-amino acid peptide, one of a new class of compounds in the field of smooth muscle relaxation and fibrosis. Based on its demonstrated effects in pre-clinical models and safety in clinical trials, AZX100 is currently being evaluated for commercially significant medical applications such as the prevention or reduction of hypertrophic and keloid scarring, treatment of pulmonary disease and intimal hyperplasia. Capstone has an exclusive worldwide license to AZX100. Chrysalin, the Company’s novel synthetic 23-amino acid peptide, has been proven in multiple pre-clinical and clinical models to stimulate cellular events leading to angiogenesis, revascularization, and repair of dermal and musculoskeletal tissues. It is currently being evaluated in disorders that involve vascular endothelial dysfunction, such as acute myocardial infarction and chronic myocardial ischemia. The Company owns exclusive worldwide rights to Chrysalin.

Brioschi, C. et al. Distribution of the pacemaker HCN4 channel mRNA and protein in the rabbit sinoatrial node. J Mol Cell Cardiol 47, 221–7 (2009).

We would like to thank Dr. Juliane Stieber for her generous gift of the human HCN clones, and Dr. Rikard Blunck for access to necessary equipment. Sources of Funding: This work was supported by a Grant-in-Aid from the Heart & Stroke Foundation of Canada (Award No. G-13-0001882). OF is supported by a bourses de prestige from GÉPROM, an FRQS funded research group.

That sounds probably legit to me. My guess would be oxidation to the iminium ion followed by hydrolysis. Nitrous acid does dealkylate some amines, as will some other oxidants sometimes i.e. strong nitric, strong chlorine sources etc. It is one of those things you won’t find in textbooks because it is pretty substrate dependent and hard to do efficiently.

(a) Differential expression of 1040 miRNAs in lung tissue from mice exposed to normoxia (21% O2)(Con) or hypoxia (10% O2) for 2 days (H-2D), 1 week (H-1W), 2 weeks (H-2W) and 3 weeks (H-3W) (n = 3 or 4 for each group). Cluster analysis of miRNAs expression from individual specimens were assessed by microarray analysis. (p < 0.05 compared with normoxic controls). (b) Validation of miRNAs upregulated by hypoxia by real-time PCR assay. Bar charts showing the relative expression level by normalizing to the respective normoxia control (Con). Data are shown as means ± SD, *p < 0.05, **p < 0.01. (c) Hypoxia results in stabilization of HIF-1α and HIF-2α proteins in the lung. Representative immunoblots showing the lung HIF-1α and HIF-2α levels in normoxia and hypoxia-exposed mice. β-actin levels served as loading control. The full-length blots with these antibodies were presented in supplementary Figure S1. All gels have been run simultaneously under the same experimental conditions.

De-differentiation rejuvenates the cell, including lengthening of telomeres.  But can the rejuvenation be done without the de-differentiation?  That’s the subject of a Cell paper by Ocampo et al.  They report success in rejuvenating cells in a living mouse, without changing them back into stem cells.  They do this via intermittent doses of the same four Yamanaka factors.  The shorter duration (2-4 days) has the effect of epigenetically reprogramming cells to their younger state, without destroying their differentiated identity.

A “Substantial Shareholder” is generally a person who alone, or together with his or her relative or another person who collaborates with him or her on a regular basis, holds, directly or indirectly, at least 10% of any of the “means of control” of a corporation. “Means of control” generally include the right to vote, receive profits, nominate a director or an officer, receive assets upon liquidation or instruct someone who holds any of the aforesaid rights regarding the manner in which he or she is to exercise such right(s), all regardless of the source of such right.

Dynavax Technologies Corporation,(NasdaqCM: DVAX) a clinical-stage biopharmaceutical company, discovers and develops a diversified pipeline of novel Toll-like Receptor (TLR) based product candidates. Based on Dynavax’s proprietary technologies, these products specifically modify the innate immune response to infectious, respiratory, autoimmune, and inflammatory diseases. Dynavax has partnerships with leading pharmaceutical companies such as GlaxoSmithKline, AstraZeneca, and Novartis as well as funding from Symphony Dynamo, Inc. and the National Institutes of Health.