A very interesting article. A bit technically dense, but the basics are pretty simple.
It explains why exercise and dietary restriction both lead to longer life and a more youthful aspect.
I’ll try to translate it to actual English ;-)
Impairment of an Endothelial NAD+-H2S Signaling Network Is a Reversible Cause of Vascular Aging
•Reduced blood flow with age is due to loss of endothelial NAD+-SIRT1 activity
•NAD+ and H2S control muscle angiogenesis and increase endurance in old mice
•The NAD precursor NMN mimics and augments exercise by inhibiting NICD-Notch
•Neovascularization is as important as mitochondria for rejuvenating muscle
A decline in capillary density and blood flow with age is a major cause of mortality and morbidity. Understanding why this occurs is key to future gains in human health. NAD precursors reverse aspects of aging, in part, by activating sirtuin deacylases (SIRT1–SIRT7) that mediate the benefits of exercise and dietary restriction (DR). We show that SIRT1 in endothelial cells is a key mediator of pro-angiogenic signals secreted from myocytes. Treatment of mice with the NAD+ booster nicotinamide mononucleotide (NMN) improves blood flow and increases endurance in elderly mice by promoting SIRT1-dependent increases in capillary density, an effect augmented by exercise or increasing the levels of hydrogen sulfide (H2S), a DR mimetic and regulator of endothelial NAD+ levels. These findings have implications for improving blood flow to organs and tissues, increasing human performance, and reestablishing a virtuous cycle of mobility in the elderly.
Having your blood not get where it needs to be is a root cause of many other symptoms of old age. They have identified why this happens and found a way to reverse it. It “mimics and augments exercise”, i.e. exercise actually does more than just use your muscles and use up calories, it also stimulates a particular regenerative pathway (NAD+ and H2S).
This stuff, NMN (nicotinamide mononucleotide) acts like exercise in that it activates that path, and mixed with exercise makes a workout work even better. It improves blood flow, capillary density, generally makes things work better as they get more oxygenation and blood flow. DR (Dietary Restriction) has similar effects.
The basic implication of this is that sitting around doing nothing while stuffing yourself (what most of the “Advanced” country population seems to do…) is a Bad Thing as it results in the opposite. Gradual decay of blood flow, oxygenation, and more rapid vascular aging. (Thus our high rates of heart attack, stroke, diabetic foot loss, etc.)
This also would explain why having your daily calorie intake cut to 1/2 the “normal” results in a 50% longevity increase and it explains why people who regularly exercise don’t mind it so much while people who do little find it a great difficulty.
So put down the Chocolate Croissant, set aside the second serving of mashed potatoes & gravy, get off the sofa, and take the dogs for a walk… Tomorrow we can work on starting that gardening project and then next week that Karate Class ;-)
IMHO, the most important word in the whole article is that one in the title. “Reversible”:
a Reversible Cause of Vascular Aging
Things that are bad and reversible really ought to be reversed.
Besides, look at the follow-on logical conclusions. Things like “I’m not going fishing just to get away from cleaning the garage, I’m doing it to work on reversing my vascular aging as it’s work porting that boat and paddling. Dear.” ;-)
Unanswered is the question of: is the effect of DR due to just gross calories, or is it more focused on particular forms of “easy calories”. While speculative, this might point at why the Ketogenic Diet seems to have such benefits. Shoving your metabolism into a state where it is changing H2S and NAD+ levels. So that, for me, would be a new “Dig Here!”. Looking for what happens in ketolysis to those pathways and signally molecules.
Now, I wonder where one gets nicotinamide mononucleotide… ;-)