Can we get back to the topic of the video in the OP?
Now that I got my methylation clock info back from DNAge and it says I'm a year older than I am, I've not only got some concerns but I'd like to know how this relates.
Hopefully I can re-explain this accurately as I understood it. Sinclaire explains how over time, we undergo epigenetic changes and lose the original "grooves" for stem cell differentiation. Nerve cells become less of a nerve cell for example, which is part of the dysfunction and one of the primary hallmarks of aging. So two questions come to mind here.
1. How does improving NAD+ levels help with this problem?
2. How do we know that restoring these levels with precursors doesn't result in further dysregulation of the salvage cycle due to an excess of NAM and a lack of NAMPT?
I don't see why you have a problem with DNAge 1 yr older Nate. Haven't you seen the other way off DNAges showing up? These tests give educated guesses at best for your changes over time with multiple testing needed. It's a metric, not an absolute.
Step back and look at the larger picture Nate that the video highlights. We're dealing with one big biochemical factory with many related reactions rate limiting others and using multiple feedback loops. Sinclair's answer (in the video) is mass doses of R, NMN, and Metformin. I hope it works out for him and his father.
Impressive - but improving the efficiency of how much and how long NR/NMN/R and associated molecules can be inserted and kept in the blood and tissues, is equally fruitful. My main N=1 right now after seeing this is Sinclair's R/NMN (can't get/want the metformin), then maximize it. I'm fortunate in that I have unlimited NMN for a time and can try whatever. Right now I feel great, better than ever. So the thought of making it better, is like making a good high, just that much higher. Or it's all placebo ... kidding.
We know aberrant methylation in aging is tied in part to NAD+ deficits, NAD+ levels are tied to many things, but H2S production and NRFx expression are important enough. And stem cell repair and rejuvenation is dependent on that and more.
An analogy might be gasoline, which is very volatile by itself, actually is a bit to explosive. So we add anti-knock compounds that slow the process, increase the useful performance, and keep the engine from blowing up! That's where I see, for example, H2S and NRFx that we've talking about here. We want to manage the process for our benefit.
I googled something like your question and found good info worth reading.
1. When stem cells grow old: phenotypes and mechanisms of stem cell aging
All multicellular organisms undergo a decline in tissue and organ function as they age. An attractive theory is that a loss in stem cell number and/or activity over time causes this decline. In accordance with this theory, aging phenotypes have been described for stem cells of multiple tissues, including those of the hematopoietic system, intestine, muscle, brain, skin and germline. Here, we discuss recent advances in our understanding of why adult stem cells age and how this aging impacts diseases and lifespan. With this increased understanding, it is feasible to design and test interventions that delay stem cell aging and improve both health and lifespan.
2. A need for NAD+ in muscle development, homeostasis, and aging
The purpose of this review is to highlight recent studies investigating NAD+ function in muscle development, homeostasis, disease, and regeneration. Emerging research areas include elucidating roles for NAD+ in muscle lysosome function and calcium mobilization, mechanisms controlling fluctuations in NAD+ levels during muscle development and regeneration, and interactions between targets of NAD+ signaling (especially mitochondria and the extracellular matrix). This knowledge should facilitate identification of more precise pharmacological and activity-based interventions to raise NAD+ levels in skeletal muscle, thereby promoting human health and function in normal and disease states.
3. NRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells
Here we show that nicotinamide riboside kinase 1 (NRK1) is necessary and rate-limiting for the use of exogenous NR and NMN for NAD+ synthesis. Using genetic gain- and loss-of-function models, we further demonstrate that the role of NRK1 in driving NAD+ synthesis from other NAD+ precursors, such as nicotinamide or nicotinic acid, is dispensable.
4. Hydrogen Sulfide Maintains Mesenchymal Stem Cell Function and Bone Homeostasis via Regulation of Ca2+ Channel Sulfhydration
Here, we demonstrate that bone marrow mesenchymal stem cells (BMMSCs) produce H2S to regulate their self-renewal and osteogenic differentiation, and H2S deficiency results in defects in BMMSC differentiation. H2S deficiency causes aberrant intracellular Ca2+ influx, due to reduced sulfhydration of cysteine residues on multiple Ca2+ TRP channels.
This topic is locked
We will see (in 8-10 weeks)!
