Reversing Aging of Mouse Blood Vessels & Muscles

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.

In Conclusion

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… ;-)

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About E.M.Smith

A technical managerial sort interested in things from Stonehenge to computer science. My present "hot buttons' are the mythology of Climate Change and ancient metrology; but things change...
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6 Responses to Reversing Aging of Mouse Blood Vessels & Muscles

  1. wyoskeptic says:

    Speaking for myself, I find that trying to stay on the ketogenic side of the equation is of major benefit. After quitting cigarettes at age 59, one of the major issues I had is one of weight control. I went from 190 to 225 in no time flat. And was still climbing. I tried the standard routine of cutting calories. The problem is that going calorie restricted while on the glucose side (high carb low fat) of things is that a person quickly has no energy. It is tough to exercise when a person is extremely hungry and facing muscle reduction which is what the body does as it tries to conserve its fat reserve (standard when the body is facing starvation).
    Trying to reduce calories when on the high carb diet means, in effect, reducing carbs (and sugar) with possibly increasing protein. If anyone is curious about the effects of this, look up either “rabbit poisoning” or protein poisoning. One report I read was about individuals who went through a winter when they were very adequately supplied with a lot of low fat meat. (Rabbits are very lean, as are most small body game.) The men grew extremely hungry and it was reported they would eat until their stomachs were distended. Some died. The body cannot exist on protein alone. They simply could not eat enough to satisfy their cravings. Other reports I read about men snowed in with little more than jerky to eat. It was said that as soon as they could find it, they would eat lard by the hands full. The body needs fats. Period.
    So, I found out about the keto diet. I added back in good fats, i.e. real butter, coconut oil, and heavy whipping cream. For my morning pick me up, I brew either a cup of tea or coffee and add a pat of butter, a good teaspoon of coconut oil (cold pressed, has about the characteristics of lard) and a generous amount of the heavy cream. (For ref, look up “bulletproof” tea or coffee.)
    My weight stabilized. I still restrict my calories, but I have all the energy I could every want, I have the endurance I used to have back in my thirties, and I am seldom hungry. I am not into the full blown ketogenic diet. What I do could be called a modified Atkins. Plenty of protein, red meat mostly, healthy fats and oils including the three mentioned above (which contain healthy MCTs — medium chain triglycerides) plus good olive oil, Omega 3 oils (fish and krill, etc.). I also include what is best described as above ground fruits and vegetables. I also do Time restricted eating. I eat one good solid meal a day, usually breakfast with little more than an apple or orange and maybe a handful or so of good nuts — shelled walnuts, almonds, or the like. I try to keep any eating to between the hours of 9 to 5. Outside of that time frame, it is nothing but water.
    Does all this work for everyone? I dunno. But for me, cutting out most of the carbs and every bit of refined sugar I can, adding in the good fats, my blood pressure has dropped. I’ve taken up biking, I can walk from 2.5 to 5 or 6 miles at a crack, have dropped my blood pressure a solid 15 on both the top and bottom numbers, as well as I can go outside and work a solid 8 to 10 hours at the pace that I used to do when working construction in my 20s and 30s. All this at age 63.
    Oh, if you look into the keto diet, one of the overlooked benefits that most msm type outlets never bother reporting on, a drop in blood pressure is common and not unexpected. Medical science blames high blood pressure on salt, but if you do some deep digging, high sugar in the diet causes much higher blood pressures than salt ever does.
    There are several doctors who get diabetic patients taking insulin completely off of insulin by way of going keto.
    If you think back to paleo caveman times, or anytime before grocery stores and sugar cane plantations, sugar, high carb foods and fruits were usually only available in the fall. Sugary foods added to the high protein high fat diets of hunters and farmers (ranchers) in the FALL tended to increase the fat supplies to help the body get through the leaner food months of winter. The human body was never intended through the centuries to exist on a high sugar diet. It runs the best on some carbs, high protein and high fats.
    By the way Keto refers to keytones, which is the alternate (I suggest preferred) fuel the body uses. The keytones are created in the liver from fats and the cells in the body does not need anything like insulin to access the keytones for energy. Research (if mouse research can be applied to humans) suggest that the heart muscles can be as much as 28% more efficient while fueled by keytones than by glucose.
    I have been exploring this rabbit hole for some time now. There is an old saying: “What is the difference between medicine and poison? Dosage.” I think this applies to sugar (and carbs are sugar in one form or another) as well. The body needs some, but when supplied in excess, is very, very damaging.
    Oh, one thing more. All those muscle and joint aches and pains? Gone. The low level depression that has been an unwelcome feature of my life through most of my adult years? Reduced to a level I seldom even notice it any more.
    Sugar is poison in excess.

  2. ray warkentin says:

    After years of yo-yo weight loss and regain of 10-15 pounds I went on the high saturated fat ketogenic diet in my mid-sixties and in a year and a half my weight went from 220 pounds to 170 pounds and has remained there. Now at 70 years of age my weight remains around 170 while I eat whenever I want without worrying about calories but just keep away from the darned carbs and treat sugar as a poison. However I am just never very hungry. A couple of years ago I started taking the NAD+ precursor supplement nicotanimide riboside (niagen). I now have more energy at 70 than I had at 50 and when in the gym push more weight than 70% of the gym-rats in their twenties. Based on my own experience I would recommend the regimen I just described. You just have to figure out a way of enjoying eating without all those carbs but I won’t try to explain all of the physiological happenings in your body when you eliminate the carbs that results in the positive effects.

  3. philjourdan says:

    Does walking cats count too? :-)

    As I donate blood every 8 weeks (due to my type), I get all their newsletters. About 3 years ago, there was an article where some doctor somewhere claimed that donating blood was good for you as it got rid of “geritol deprived blood” (my term) and forced your body to create healthy new cells. I figured that was just fluff to make us feel better (you cannot donate more than every 8 weeks in this country so it was not to get us to donate more).

    But I do let my blood do my walking for me. :-) I do the running after the cats.

  4. Chazz says:

    Amazon $26.99 for 30 ea 125 mg

  5. Larry Ledwick says:

    Dietary fat is required to mobilize stored fat. Since about 65% of our energy comes from fat metabolism at low work load efforts (ie every day activity) that becomes a bottle neck on a limited fat diet.

    I try to keep any eating to between the hours of 9 to 5. Outside of that time frame, it is nothing but water.

    You are essentially doing intermittent fasting by forcing your body to go extended periods without food intake, this increases metabolism and HGH (human growth hormone) over sedentary all day eating food intake. The body response to just straight food intake reduction and intermittent intake of reasonable amounts of food are very different. If you eat all day but take in limited food, your body thinks you are starving and begins cannibalizing itself to meet its needs. If you go long times between food intake (12-24 hours) but eat a reasonable amount of food, your body just thinks hunting is a bit lean and you need to run faster to catch the next rabbit, so it actually ramps up HGH for faster muscle repair and to limit cannibalization of lean muscle, and also ramps up metabolism to make you a more efficient hunter.

    I went on a planned stretch of intermittent fasting last year and dropped 30 pounds about .25 – .3 pounds a day if I stuck with it. Work has not been cooperating this winter so I dropped back into old habits and put much about 10-12 pounds back on this winter.

    Mountain climbers and out doors types working in arctic conditions get hungry for fats, and will literally eat bars of butter like a candy bar when starved for fats.

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