Viagra and Cialis, and a third, lesser known drug, Levitra, are used to treat erectile dysfunction. Use of these drugs is associated with a lower risk of heart attacks, and can be used as therapeutics against other disease. Will Viagra and Cialis extend lifespan?
PDE5 inhibitors
Erectile dysfunction drugs such as Viagra inhibit an enzyme called phosphodiesterase 5, or PDE5. Phosphodiesterase enzymes have varying subtypes, and are found in all tissues. They catalyze the breakdown of two molecules, cGMP and cAMP, into inactive compounds.
PDE5 is upregulated from 2- to 5-fold in human heart disease. Inhibition of PDE5 with sildenafil (Viagra) protects against ischemia/reperfusion injury, which means it increases cellular antioxidant protection mechanisms.
In diabetics, use of PDE5 inhibitors is associated with a 31% decrease in all-cause mortality. After adjustment for age and other factors, mortality risk decreased to nearly 50%, including a 38% lower incidence of heart attack.
PDE5 expression is increased in many human cancers, and a number of studies have suggested that PDE5 inhibitors may be therapeutic against cancer.
Why PDE5 inhibitors fight aging
Mikhail Blagosklonny, M.D., the noted scientist who studies aging, mentioned PDE5 inhibitors as part of a suggested, or testable, anti-aging drug combination, along with rapamycin, metformin, aspirin, ACE inhibitors, and beta blockers. He writes that they are remarkably safe and are already being used in the treatment of pulmonary hypertension.
Levels of the enzyme PDE5 appear to rise with age, and therefore inhibiting them can bring them to youthful levels, and prevent or help to treat diabetes, heart disease, and cancer.
PDE5 inhibitors increase the level of nitric oxide (NO), which is important for endothelial (vascular) function; that’s how they work to increase erectile function.
Why would they help decrease heart attacks in diabetics?
In mice, tadalafil (Cialis) lowers blood glucose and triglycerides, which entails an increase in insulin sensitivity. It also decreased inflammatory markers.
Also in mice, sildenafil (Viagra) improves cognitive function.
What I’m waiting for is a study that shows PDE5 inhibitors increase lifespan in normal laboratory animals. My guess is that this will happen – probably someone is already working on it. A drug that fights all of the main diseases or signs of aging, namely cancer, heart disease, diabetes, and cognitive decline, is one that fights aging itself, since aging is the underlying driver of all of these problems.
Another way to put it is that these drugs may not only increase median lifespan, which is what a drug that fights one disease does, but maximum lifespan, which is what a drug that fights aging does.
In C. elegans, the worm that is so often used in studies of aging, cGMP increases lifespan via the insulin-signaling pathway. PDE5 inhibitors work by increasing cGMP.
Safety
As mentioned, PDE5 inhibitors appear quite safe. As a testimony to that safety, in the U.K., Viagra can now be sold over-the-counter (OTC), and no prescription is required. I expect the U.S. and other countries to follow suit.
Half-Lives
The PDE5 inhibitors have varying half-lives, which is the time it takes for half of the drug to be metabolized or otherwise removed from the body.
The half-lives are:
- sildenafil (Viagra), 3-4 hours
- vardenafil (Levitra), 4-5 hours
- tadalafil (Cialis), 17.5 hours
If used for treatment of disease or to fight aging, as opposed to erectile dysfunction treatment, Cialis has an obvious advantage, since it can be taken once a day. Long-term tadalafil was found to be safe and well-tolerated. Note, however, that this study was funded by Lilly, the manufacturer of Cialis.
Conclusion
In a sense, it’s no surprise that PDE5 inhibitors appear to be so effective in treating age-related diseases. Since erectile dysfunction is so closely associated with aging, any drug that restores erectile function is effectively restoring youth, just as a drug that restores insulin sensitivity (metformin) also does.
I expect these drugs to become even more widely prescribed in the future.
PS: For more on how to extend lifespan, see my book, Stop the Clock.
18 Comments
Thanks for another great article, however a slight quibble…Blagosklonny is actually talking about ARBs, not ACE-class drugs, although he confusingly mentions ACEs. I have been taking several ARBs and haven’t noticed anything bad and possibly something good, but it’s too soon to say for sure. The trick with those seem to be figuring out when lowered blood pressure becomes a risk for the kidneys, which I have been looking for guidance on but have not found yet.
As side notes, it seems curious that he doesn’t mention CBD oil. It seems to have had an amazingly beneficial affect for me on residual muscle stiffness, and in looking at its actions, it seems to block inherently harmful forms of inflammation.
Also, I seem to remember Beta blockers having some potentially major issues although I don’t remember the details right now, but I’ll try to track them down and perhaps others can chime in.
He mentions both, and both are effective.
Thanks, I sit corrected. I had seen studies showing a life-extension outcome for ARBs independent of BP but not for ACE inhibitors. After some more reading, it looks like trying a combination of both may be the best-supported path.
Would Arginine have similar benefits? That might be a more cost effective long term approach.
Citrulline is what you want, since arginine is extensively metabolized in the gut and isn’t absorbed well. Does the same as PDE5 inhibitors, not as effective though. See here.
Nice article. I self experimented with daily cialis after reading the Blagosklonny paper but it gave me headaches. Citrulline with 200mg of pine bark worked as well without the side effects to elevate NO levels.
Ace and arb’s both work to ultimately inhibit the action of angiotensin. I tried both but my bp’s got too low.
There is very significant data out of China that the non selective beta blockers like propanol reduce cancer incidence by a whopping 50%. Not so with the selective ones that are now prescribed.
Happy Holidays
I take a very low-dose beta blocker (metaprolol) daily. I initially started taking it to correct an irregular heartbeat that was annoying, but not a serious health issue (premature ventricular contraction). It corrected that problem immediately, and I was going to stop taking the metaprolol, but I did a lot of research on it, and found several studies indicating that metaprolol extends the median lifespan of mice, and “may” do the same for humans. So, I continue to take it, since I have noticed zero side effects. Metaprolol also reduces blood pressure slightly (at the dosage I take), which may be a good thing as well. Here is one study on metaprolol and mice longevity: https://link.springer.com/article/10.1007/s11357-012-9498-3?no-access=true
It does extend lifespan in those who are at risk for cardiovascular disease, as any beta blocker would , but the non-selectives like propanolol have the added benefit of reducing cancer risk and overall mortality, but the downside is the possibility of fatigue . It’s becoming increasingly clear that reducing sympathetic tone and increasing parasympathetic tone are important interventions, if they can be done safely, and so at this point exercise may be the best option.
My late father was diagnosed with heart disease at age 49 – angina. He was prescribed propranolol and took it for the rest of his life, which reached the age of 87. I can’t help but think that had a lot to do with his relatively long life, considering he was ill the whole time.
PD is hacking even the death.
Also Low-dose Tadalafil also shows good results in treating Benign Prostate Hyperplasia (BPH). one possible mechanism would be the effects on PDE11 in muscle tissue as well as PDE5. (Hyperplasia in an organ that is directly affected by sex hormones does not seem all that Benign to me, but that is a different topic)
Medline paper on PDE5 inhibitors and BPH
https://www.medscape.com/medline/abstract/19887943
BPH is associaed with Lower Urinary Tract (LUTS) problems that PDE5 inhibitors can relieve, it is possible that microvascular dysfunction is involved in LUTS and is relieved by the PDE5 inhibitors- that would explain some of the cardiac improvements via microvascularity issues elsewhere in the body, such as the heart.
https://www.ncbi.nlm.nih.gov/pubmed/24619381
https://www.bioportfolio.com/resources/pmarticle/966081/Microvascular-dysfunction-and-efficacy-of-PDE5-inhibitors-in-BPH-LUTS.html
The PDE5 inhibitors are peptides, there are sources online for them easily found via any search.
What about hemp milk with beet juice and NAC. Often times I had to stop my workout and look for my wife cos I was all excited. What I notice was creatine has the opposite effect on me, no sex drive. Happy holidays.
As a 71 year old man interested in health, including, of course, “men’s health,” I’ve done a lot of research and experimentation of the PDE5 inhibitors. IIRC, Viagra’s sex benefit came as a rather unexpected side effect of using it for cardiac health, as you mention. “Well, doc…………..”
I’ve also found a paper that with a year of 50mg/day, IIRC, a huge percentage of men with ED became cured.
Don’t look for any of these becoming OTC any time soon in the USA. There are six lobbyists in Washington for every single man and woman in congress. “Boner meds” are a huge cash cow. I get mine from India,
I have found an incredible way to inhibit my PDE5: Be in mutual love with a beautiful woman 20 years younger who is insatiable. No pills necessary, although we find we have even more fun with them.
Between good genes for very long life, aspirin and giving blood, Vit. D and K2, a good diet, and the known benefits of sex and love, I’m in it for the long haul.
I saw this article today about Lactobacillus reuteri, and thought it might be something worth adding to the discussion about anti-aging drugs/supplements. I’m not promoting or endorsing this in any way…….just putting it out there for information/discussion:
https://www.wheatbellyblog.com/2018/01/lactbacillus-reuteri-key-youthfulness/#comments
Thanks, Rob, I wrote about L. reuteri here.
During my constant research on matters of health, I read (sorry, no cite!) that women who had an overt, easily found G-spot had higher levels of PDE5.
Not sure what that might mean about anything, but there ya go. PDE5, bad for men, good for women? What do I know?
You’ve had your time grandpa. Stand aside for the new generation.
Poast physique.