To this discussion I repost the paper by Bush et al because it goes so nicely with what Dr. Sinclair is telling and how my way of thinking changed after the "Rubidium"-paper by Masters et al ( first author Roberts ) in Nov 2016. All cells accumulate iron when they are get old. This means that all cells start having energy problems, those organs first needing most of the energy (brains, heart ) but practically all organs. This is why these organs start failing and we get symptoms of any organ when we get old almost at the same time during our last years. The common thing in these organs can very well be the mitochondria suffering poor function. Sinclair things that this problem is not a problem separately in the heart, or bone, or else but it is a problem common to all these organs, their poor energy supply and when we can take care of that we can get help to all organs by a single drug . Now we know that accumulating iron hampers mitochondria and Prana has the drug to help iron overload.So if things are as they now look and as Dr Sinclair things and has invested in Prana few millions we other investors are also safe with Prana. There are few problems of course (phase 1, 2, 3) and this is why SP is still on a very low level.
Here is the paper: Redox Biol. 2018 Apr;14:100-115. doi: 10.1016/j.redox.2017.08.015. Epub 2017 Sep 1.Iron accumulation in senescent cells is coupled with impaired ferritinophagy and inhibition of ferroptosis.Masaldan S1, Clatworthy SAS1, Gamell C2, Meggyesy PM1, Rigopoulos AT1, Haupt S3, Haupt Y4, Denoyer D1, Adlard PA5, Bush AI5, Cater MA6.Author informationAbstractCellular senescence is characterised by the irreversible arrest of proliferation, a pro-inflammatory secretory phenotype and evasion of programmed cell death mechanisms. We report that senescence alters cellular iron acquisition and storage and also impedes iron-mediated cell death pathways. Senescent cells, regardless of stimuli (irradiation, replicative or oncogenic), accumulate vast amounts of intracellular iron (up to 30-fold) with concomitant changes in the levels of iron homeostasis proteins. For instance, ferritin (iron storage) levels provided a robust biomarker of cellular senescence, for associated iron accumulation and for resistance to iron-induced toxicity. Cellular senescence preceded iron accumulation and was not perturbed by sustained iron chelation (deferiprone). Iron accumulation in senescent cells was driven by impaired ferritinophagy, a lysosomal process that promotes ferritin degradation and ferroptosis. Lysosomal dysfunction in senescent cells was confirmed through several markers, including the build-up of microtubule-associated protein light chain 3 (LC3-II) in autophagosomes. Impaired ferritin degradation explains the iron accumulation phenotype of senescent cells, whereby iron is effectively trapped in ferritin creating a perceived cellular deficiency. Accordingly, senescent cells were highly resistant to ferroptosis. Promoting ferritin degradation by using the autophagy activator rapamycin averted the iron accumulation phenotype of senescent cells, preventing the increase of TfR1, ferritin and intracellular iron, but failed to re-sensitize these cells to ferroptosis. Finally, the enrichment of senescent cells in mouse ageing hepatic tissue was found to accompany iron accumulation, an elevation in ferritin and mirrored our observations using cultured senescent cells.
