Summary
Sirtuins important role in aging. Silence certain genes (control epigenome) and alternate between that role and fixing DNA.
- As we age the back and forth causes loss of information on the program. Loss of info = Sirtuins don't go back and forth at precisely correct times = cells lose their identity, shape, function. Genes that were supposed to be on now off and vice versa. Often upregulated by stress (heat, salt, lack of nutrients). Destruction of epigenome (expression of gene on/off)
Can slow this aging by getting cells to behave as if they were 20 years old again. Still know when to turn specific genes on/off, dont stay distracted by stress (DNA repair ex)
NAD (NADH, NAD+) required for Sirtuins to work (also required for dozens of other reasons!)
- NR —> NMN —> NAD (lots of OTC drugs focus on precursors)
There are layers to gene expression (epigenome). Mythelation is the deepest and is semi permanent turning off/on of genes, - its how we can have stem cells turn into either skin or hair or liver etc cells...lose this info/function by Sirtuins and cells lose identity..
- Horvath clock is math function to measure this deterioration over time and determine age by measurig mythelation. This should be more stable than telomere measurements.
There may be a master copy of mythelation in each cell unaffected...can revert cell back to newborn status (post stem cell but before loss of info/identity. Lower Horvath clock number. This is forefront of anti-aging.
Metaformin, Rapamycin, Resveratrol and caloric restriction lengthen peoples lives but not without presence of Sirtuins.
Interventions such as rapamycin, NAD booster, Metformin – impact the superficial layer where transcription factors singal which genes to be read or not – slow down aging but they cannot reverse it. Need gene reprogramming to put mythelation back to when we were born.
Current cutting edge research is focusing on injecting Yamanaka genese to re-program cells back to earlier versions of mythelation.
Using Horvath clock math can impute earlier "younger" versions of gene expression.
Not sure where "master copy" is being read from but seems like cells have ability to reset on/off expression. Studies in mice have enabled restoration of vision through this therapy.
Bottom line - we don't lose the information (DNA or gene mutation), instead we lose ability of Sirtuins to precisely regulate genes on/off. Appears there is master copy of this we can reset back to.
Steps to take:
- Calorie Restriction - no harm, cheap, turns on Sirtuins, autophagy
- Exercise - same as CR, no brainer.
- Resveratrol - cheap, prob doenst hurt, activates sirtuin. Wine doenst have enough. take 1 gram/day with fatty food
- NR/NMN/NAD+: worth taking, necessary for energy, sirtuin activation, levels go down with age. Problem is they dont know best dose/precursor/method of administration. 100 mg of NR under tongue is a good place to start.
- Metformin - need a Rx, probably not worth it in healthy people
- Rapamycin - steve to do more research, but seems similar to metformin
Very popular NAD supplements
- Basis by Elysium (includes pterostilbene, which is a sirtuin activator)
- Tru Niagen by ChromaDEX (no sirtuin activator)
Oral NR should work, but it saps your methyl groups. Which hurts creatine production. Can take creatine or TMG mg for mg