Blood Pressure Drugs Extend Lifespan

Common and cheap blood pressure drugs extend lifespan in animals by inhibiting the renin-angiotensin system. This pathway for life extension is both different from other pathways, such as mTOR or the insulin/IGF-1 pathways, and intertwined with them.

Renin-Angiotensin System

Animals, including humans, finely control blood pressure through both hormones and the nervous system. Blood pressure control is very important, since loss of blood pressure can lead to shock and death, for instance in blood loss, or in extreme illness.

Two hormones, renin and angiotensin, regulate blood pressure. The kidneys secrete renin which, in case of low blood pressure, cleaves angiotensinogen to make the hormone angiotensin I, which is then converted by angiotensin converting enzyme into angiotensin II, a potent peptide which acts to constrict blood vessels in order to raise blood pressure. Angiotensin II also causes the secretion of yet another hormone, aldosterone, which in turn causes the kidneys to retain more sodium and water, which also raises blood pressure.

Hypertension, or high blood pressure, promotes cardiovascular disease, including heart attacks and stroke. Lowering high blood pressure is considered an important strategy in preventing heart disease and stroke.

Anti-hypertensive drugs have several different mechanisms, but for the purposes of this article, and seemingly most importantly for life extension, we’ll focus on two types of drugs that affect angiotensin, namely angiotensin converting enzyme (ACE) inhibitors, and angiotensin receptor (AR) blockers. There seems to be little difference in effectiveness between ACE inhibitors and AR blockers in terms of mortality, at least in certain classes of patients.

Blood pressure, aging, and life extension

It’s well known that blood pressure tends to rise with age.

Of course, as people get older, they get fatter and lose muscle, insulin resistance increases, and they become more sedentary, and those factors all affect blood pressure.

Yet aging itself seems to be a factor even absent these. Blood pressure rises with age in lab animals, for instance.

In mice, disruption of the angiotensin II receptor increases lifespan. Not only that, but the increase is large, as large as that caused by insulin receptor disruption. See chart below.

Knocking-out AT1A prolongs life span in the mouse. A Kaplan-Meier an...

The average lifespan of normal mice was 24 months, that of genetically disrupted angiotensin receptor knockout mice was 31 months, about a 26% increase. When all the wild-type animals had died, 85% of the knockout mice were still alive. Body weights and physical activity between the two groups were the same, so this was not an artifact of reduced food intake, i.e. calorie restriction. (Many life-extension treatments appear to work by inducing lower food intake.)

However, another study found that long-term angiotensin inhibition resulted in less fat tissue.

In rats, long-term angiotensin blockade exerts “a significant protective effect on the function and structure of the cardiovascular system in all treated animals.” Of interest, the animals were divided into 3 groups: control (no treatment), a group treated with an ACE inhibitor, and a group treated with an AR blocker. There was no difference between the 2 treatments, which “clearly indicates that most of the effects are exerted through AT1 receptors. An outstanding finding was the significant and similar prolongation of life span in both groups of treated animals compared with untreated control animals.” The average survival of the control group was 735 days, while the two treatment groups lived 892 and 877 days, respectively, a large effect.

ACE inhibitors even robustly extend lifespan in the worm C. elegans which surprisingly have a a molecule homologous to ACE.

In spontaneously hypertensive rats, ACE inhibition doubles the lifespan to that of normal rats. Maybe that should be expected; another way of saying this is that spontaneous hypertension halves lifespan. However, it does show the crucial importance of blood pressure.

In cell culture, resveratrol downregulates angiotensin receptor expression. Since resveratrol functions as a calorie restriction mimetic, this shows that yet another way that calorie restriction extends lifespan may be through its effect on angiotensin receptors.

Indeed, obesity increases the activity of the renin-angiotensin system. Weight loss in humans decreases expression and activity of the system.

Calorie restriction and angiotensin inhibition “display a number of converging effects, i.e. they delay the manifestations of hypertension, diabetes, nephropathy, cardiovascular disease, and cancer; increase body temperature; reduce body weight, plasma glucose, insulin, and insulin-like growth factor-1; ameliorate insulin sensitivity; lower protein, lipid, and DNA oxidation, and mitochondrial H2O2 production; and increase uncoupling protein-2 and sirtuin expression.”

So, can you get all the effects of calorie restriction just by inhibiting the angiotensin system? Could be, yes.

“…both animal and human evidence show that RAS blockade can prevent age-related structural and functional alterations in several organs, progression to the metabolic syndrome, the development of diabetes, hypertension and some of its consequences, cardiovascular changes, and cerebral and cognitive impairments. The latter conditions act as surrogate markers of the ageing process, and at the same time, they accelerate age-related structural and functional decay in various tissues.” (Above ref.)

Oddly enough, there’s an iron connection. Namely:

Blocking angiotensin is about much more than blood pressure. Patients treated with angiotensin blockers had quite a bit better survival than patients treated with beta blockers, even with both groups having the same reduction in blood pressure.

Another class of anti-aging drug

The 3 most powerful anti-aging drugs appear to be rapamycin, metformin (or the similar supplement, berberine), and aspirin. There are other drugs and supplements that promote life extension, such as resveratrol and curcumin, and it’s difficult to make direct comparisons as to which of these are better, or which combinations, etc., but the first 3 are generally accepted as having the most potential to extend human lifespan.

We might be able to add a fourth class of drugs to the list of powerful life-extension agents, namely those that affect and inhibit the renin-angiotensin system, i.e ACE inhibitors and AR blockers.

Both classes of these drugs are widely used to lower blood pressure. They’re also quite cheap, perhaps a few dollars a month for either. When taken in low doses, they seem to have few side effects, and as far as I can tell, doctors are not hesitant about prescribing them.

Of the drugs mentioned above, only rapamycin is expensive.

Alan S. Green, M.D., who practices rapamycin-based treatment of diseases of aging, uses ACE inhibitors as part of his anti-aging regimen, in addition to rapamycin, metformin, and aspirin.

I’ll be posting an interview with Dr. Green soon.

My new book, Best Supplements for Men, has an extensive section devoted to life extension supplements.

PS: Check out my Supplements Buying Guide for Men.

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Leave a Comment:

13 comments
Stuart Mather says June 3, 2017

I My blood pressure has been close to the low end of normal for my entire life, so blood pressure reducing medication isn’t for me. But I’m wondering whether metabolisms like me get the same benefits of the angiotensinjust receptor inhibition from having naturally low blood pressure. ?

I’ve taken low dose berberine aspirin, resveratrol,for over a decade. Rapamycin’s too expensive though.

Reply
    P. D. Mangan says June 4, 2017

    Hi Stuart. I’m not sure, but I’m inclined to think that there is benefit. In lab animals, anti-angiotensin treatment prolonged life, seemingly so even in the absence of hypertension. On the other hand, back here in the real world, one side effect of blood pressure drugs can be fatigue, which may be related to low blood pressure, so whether one wanted to take an anti-hypertensive drug anyway would be up to one’s doctor as well as personal choice as to whether a side effect like fatigue was worth it.

    Reply
    Allan Folz says June 5, 2017

    Over a decade? That’s interesting, Stuart.

    My biggest concern with, call them non-dietary supplements, which is to say the substances that one cannot get via diet in any appreciable amount, is the possibility of adverse the long-term side-effects.

    By way of background, I started out mostly passing Dennis’ advice on to my Father, as at 40 years old (well, back then I was 40) I felt most of it didn’t much apply to someone my age. After a while, I succumbed to the message and started putting Dennis’ advice into practice myself, largely on the reasoning that an ounce of prevention is better than pound of cure. While I don’t feel I’ve rolled back the clock to my 20’s or even early 30’s (those self-reports alway flabbergast me), I can say I feel as good now as my late 30’s, and certainly better than the trajectory I felt I was on at 40: I’m now 44. Instead of more of the same downward drift, 39->42 had a definite “wow, so this is aging… that sucks,” from 42 to 44 I can say I feel no worse than 39, and insofar as I began strength-training ~15 months ago, I am in that regard, much better than 39.

    With that as is lead-in, do you mind sharing some of your own health details — age, current fitness, general activeness level & whether its changed substantially (ie. former couch potato vs. always doing one sport or another) — and what your thoughts are and experience of taking these supplements on a long-term basis has been?

    One more thing I’ll offer, as my age-cohort of friends have largely hit the wall on their outward appearance, I feel I’m still doin’ OK and could hold my own with all but the best of them. I’m not in the Naiman/Baker tier, but I don’t feel I have anything to be sheepish over. 🙂

    OK, last thought… also not gone unnoticed by me has been Dr’s Kraft & now Kummerow living a good long while, which is encouraging.

    Reply
Stuart Mather says June 3, 2017

I should also add that I also have always had rreally low levels of serum ferritin. Hemoglobin’s okay though. Just. I’d donate blood a lot more often than I do for fear of letting my iron get too low. Love red meat….

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Nathan Viles says June 4, 2017

It’s worth mentioning a rare and potential y deadly reaction to ACE inhibitors known as angioedema. If one were to start using an ACE inhibitor it would be wise to educate yourself on angioedema
.

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Ole says June 4, 2017

Looking very much forward to your interview with Mr. Green. If the results he has had with rapamycin can be broadly repeated, this could be a potential game changer for people above the age of 60.

Reply
Thinker says June 4, 2017

People taking ACE inhibitors or beta blockers cannot get allergy desensitization injections.
Because the drugs interfere with Epinephrine. There may be other issues involving food allergies and ACE inhibitors but it is not clear.

Reply
brbr says June 5, 2017

What would be the best blood pressure drugs, or are they all the same. I used to take losartan, might consider going back to it.

Also, any equivalent drug to rapamycin for poor guys like me? (like berberine is for metformin and vice-versa).

Reply
    P. D. Mangan says June 5, 2017

    It appears that angiotensin blockers (like losartan) and ACE inhibitors are equally effective, and both are more effective for anti-aging than beta blockers, although the latter works too. There doesn’t seem to be anything equivalent to rapamycin, though it’s an mTOR inhibitor, and many other supplements do that, just less effectively.

    Reply
beto says June 5, 2017

But what pressure should you start with Mediacamento? If the pressure increases with age, which is true, the use of medication should start on the marker above, in such a way that supposedly hypertension would be considered normal in the elderly. OK?

Reply
    P. D. Mangan says June 5, 2017

    I couldn’t say at what pressure to start. While high blood pressure in older people could be considered “normal”, it’s still bad. In some of the animal experiments, even animals with normal blood pressure were placed on the drugs, and lived longer. Mikhail Blagosklonny advocates them even for normotensive older people. However, my understanding is that blood pressure drugs can cause fatigue, especially in the normotensive.

    Reply
Joshua says June 13, 2017

Interesting writeup. I don’t believe I’ve seen this mentioned elsewhere. I think the next question is — is there a “natural” — or at least non-prescription — version of an ACE inhibitor or AR blocker? Or certain foods that contain compounds that have this effect? (Holy grail would be that wine does it, but I doubt that.)

Reply
    P. D. Mangan says June 13, 2017

    Hi Joshua, it was new to me too. I looked around for “natural” angiotensin blockers, but any that I found appeared quite weak.

    Reply
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