The Nitric Oxide (NO) Theory Of Aging

[lollipop]

If you're in that situation then I think the problem is more that you're actually still not in good health just applying some bandaid to cope with symptoms - good health necessarily implies some robustness, so you could handle a change for a while without noticing much. Like when you were a kid. Like eating junk food or skipping meals on a busy day, if you're in good health then going through that is no problem to repair - you wouldn't go sick for the afternoon. A rigid metabolism is a common indicator of poor health, look up articles on "metabolic flexbility".

@jyb what you said here makes sooooo much sense to me.

 

[Makrosky]

If you're in that situation then I think the problem is more that you're actually still not in good health just applying some bandaid to cope with symptoms - good health necessarily implies some robustness, so you could handle a change for a while without noticing much. Like when you were a kid. Like eating junk food or skipping meals on a busy day, if you're in good health then going through that is no problem to repair - you wouldn't go sick for the afternoon. A rigid metabolism is a common indicator of poor health, look up articles on "metabolic flexbility".

That's exactly what I meant jyb. Nice to see someone thinks the same.

 

[Amazoniac]

https://www.researchgate.net/publication/7371709_The_Nitric_Oxide_Theory_of_Aging_Revisited

 

[haidut]

https://www.researchgate.net/publication/7371709_The_Nitric_Oxide_Theory_of_Aging_Revisited

Thanks, posted it in the main thread.

 

[Amazoniac]

Thanks, posted it in the main thread.

I'm curious, why didn't you post their updated article on the original post? It was already available when you created this thread and shown on the "related/suggested" PubMed list. I figured there must be a reason..

 

[haidut]

I'm curious, why didn't you post their updated article on the original post? It was already available when you created this thread and shown on the "related/suggested" PubMed list. I figured there must be a reason..

Simple - I found it browsing on my phone at the time and since it showed the mobile version of PubMed and there were no recommended/related studies shown.

 

[ddjd]

Agmatine seems to do the same - lower all forms of NO, but in a few studies, does seem to enhance the eNOS

Anyone else confused about the various isoforms of NO?

Yes I noticed Agmatine actually raised my Nitric oxide

 

[Blake]

How to lower NO from high Serotonin

 

[Capt Nirvana]

Just like estrogen, NO has physiological role but it is limited and reserved for times of stress. With the exception of Viagra pretty much all other drugs on the market that deal with NO actually try to lower it, not raise it. And in the case of Viagra, look at its side effects and the studies on PubMed for its long term use - short term it can cause heart attacks and/or strokes, while chronically elevated NO causes CVD, MS, AD, PD, and other degenerative conditions. So, NO has its use but is not a marker of health and just like the study you posted said, if you want broncho/vasodilation you can get it from CO2. If NO was that good for bronchodilation, why would doctors try to lower it in patients with asthma? See this:

http://www.atsjournals.org/doi/full/10. ... 310-1473OC
Caffeine opposes the effects of NO and its release pretty much anywhere in the body, so if caffeine is in general beneficial and it acts in a manner opposite to NO then I don't see how chronically elevated NO can be good. Similar to aspirin and estrogen. Estrogen is needed for cell division, growth, healing, but unopposed becomes carcinogenic and that's why we need aspirin to restrain it.

Carbon monoxide and hydrogen sulfide are also neurotransmitters that do most of the things nitric oxide does, but we don't see people lining up to buy them as supplements at health food stores. Automobile accidents and visits to the IRS are two of the best ways to supplement with nitric oxide. Living in Los Angeles used to work too, but the air is cleaner nowadays. :)

 

[Capt Nirvana]

Somehow I double-posted the above post. Apologies.

 

[benaoao]

Confused by this thread, as PDE5 inhibitors have interesting long term benefits according to pubmed

Useful Implications of Low-dose Long-term Use of PDE-5 Inhibitors. - PubMed - NCBI

Oral phosphodiesterase type 5 inhibitors: nonerectogenic beneficial uses. - PubMed - NCBI

And many others.

 

[ecstatichamster]

Confused by this thread, as PDE5 inhibitors have interesting long term benefits according to pubmed

Useful Implications of Low-dose Long-term Use of PDE-5 Inhibitors. - PubMed - NCBI

Oral phosphodiesterase type 5 inhibitors: nonerectogenic beneficial uses. - PubMed - NCBI

And many others.

Very doubtful studies. Drug companies have relentlessly promoted these for decades.

 

[haidut]

Carbon monoxide and hydrogen sulfide are also neurotransmitters that do most of the things nitric oxide does, but we don't see people lining up to buy them as supplements at health food stores. Automobile accidents and visits to the IRS are two of the best ways to supplement with nitric oxide. Living in Los Angeles used to work too, but the air is cleaner nowadays. :)

Lol, I like your style! Doesn't eating a lot of broccoli/cabbage/etc raise hydrogen sulfide?

 

[benaoao]

Very doubtful studies. Drug companies have relentlessly promoted these for decades.

no, drug companies haven't promoted low dose off label use of pde5 inhibitors for decades.

 

[ddjd]

no ones mentioned hair loss in this thread. Could nitric oxide be the primary cause of hair thinning and possibly the starting point for the cascade of other stress hormones and neurotransmitters - cortisol, estrogen, serotonin etc.

I personally think low co2 and high nitric oxide is the key reason for hair loss

 

[dreamcatcher]

I recently found this study and decide to make a post about it. Ray has written a lot about NO, but in the allopathic medicine NO has pretty good reputation due to drugs like Viagra and drugs for pectoral angina (chest pain). So, I did not expect to run into that study on PubMed and thought that the study deserves a discussion.

The nitric oxide hypothesis of aging. - PubMed - NCBI
https://www.researchgate.net/publication/7371709_The_Nitric_Oxide_Theory_of_Aging_Revisited

The studies make some pretty sweeping conclusions, mainly along the lines that NO is one of the main causes of aging. In addition, the studies talk about two major themes of Peat's - i.e. endotoxin generating NO in the body and brain, and tetracycline antibiotics directly helping reduce NO production.
Finally, these studies overlaps a bit with my most recent post on tryptophan depletion (ATD). ATD causes daramatic drop in levels of both NO and its precursors arginine and citrulline, which probably explains many of the life-extending effects of tryptophan-restricted diets.

Here are some quotes from the first study, with some of the salient points underlined.:

"...At the Third International Symposium on the Neurobiology and Neuroendocrinology of Aging, I (McCann, 1997) presented evidence to suggest that excessive production of the free radical, nitric oxide (NO), in the central nervous system (CNS) and its related glands, such as the pineal and anterior pituitary, may be the most important factor in aging of these structures. Evidence for this hypothesis has been accruing rapidly. Because of the fact that the synthesis of inducible NO synthase (iNOS) following injection of bacterial lipopolysaccharide (LPS) in the rat was much greater outside the blood– brain barrier (Wong et al., 1996), for example, in the anterior pituitary and pineal gland, than inside this barrier, it occurred to us that NO might play a role in aging of every organ system of the body. The evidence for this concept is particularly well developed to explain the pathogenesis of coronary arteriosclerosis."

"...NO blocks cellular enzymes required in metabolism and also activates soluble guanylate cyclase (sGC), a soluble enzyme present in the cytoplasm of cells. The activation occurs via interaction of NO with the Fe21 in the heme portion of the molecule, thereby altering its conformation and activating it."

"...Furthermore, NO also inhibits the release of both norepinephrine and dopamine from the medial basal hypothalamus, constituting another negative feedback of pulsatile LHRH release by feeding back on the terminals of the noreadrenergic and dopamineric neurons to inhibit the release of both of these transmitters, one of which, and probably both of which, stimulate the release of NO that drives LHRH release (Seilicovich et al., 1995b)."

"...We hypothesize that the pulsatile release of GH that occurs under normal conditions is brought about principally by NO stimulation of GH-releasing hormone (GHRH) release."

"...The IL-induced prolactin release is also mediated by NO (Rettori et al., 1994b) probably by NO stimulation of prolactin releasing peptides, such as oxytocin (Rettori et al., 1997) and by inhibition of the release of dopamine, a potent prolactin release inhibiting hormone, into the hypophyseal portal vessels (Duvilanski et al., 1995)."

"...Adenosine is secreted by the FS cells, and is the most powerful stimulant of prolactin secretion from anterior pituitaries in vitro yet identified, increasing release at concentrations of 10e10–10e5 M with maximal release of three times basal at 10e28 M."

"...These results raise the possibility that even moderate infection, without direct CNS involvement, can increase iNOS levels and lead to production of toxic levels of NO. Therefore, it is possible that repeated infections over the life span could lead to brain damage in areas where there is large induction of iNOS in neurons, such as the PVN—the site of the cell bodies of most of the releasing and inhibiting hormone neurons—and the AN-median eminence region, which is also the site of production of GHRH, many neurotransmitters, and the site of passage of axons of many of the releasing hormone neurons, such as LHRH neurons, which project to the median eminence. There may also be damage to glial elements, meninges, and to the choroid plexus over the lifespan. The induction of IL-1a neurons in the temperature-regulating regions of the preoptic area should also be followed by induction of iNOS. Exposure to high levels of NO in this region may kill thermosensitive neurons and thus be responsible for the decreased febrile response to infection in the elderly. Measurement of iNOS activity in aged male rats (greater than two years of age) revealed a significant increase in NOS activity in comparison with that in young adults, which provides the first experimental support for this concept (Rettori,
unpublished data)."

"...These findings provide an explanation for the high incidence of early onset Parkinsonism in many people who served in World War I and developed influenza. There was a major epidemic of influenza with encephalitis, which presumably led to generation of large amounts of NO in the region of the substantia nigra that then caused loss of dopaminergic neurons and eventual development of Parkinsonism many years before it would have appeared as a result of normal aging. The appearance of Parkinsonism with age is probably related to the quite rapid decline, beginning at age 45, in dopaminergic neurons in this region even in normal individuals (Knoll, 1997), which may also be caused by enhanced NO generation during infections."

"...A great deal of evidence has accrued, suggesting the possibility that chronic infections may have a relationship with coronary heart disease (CHD) (Danesh et al., 1997). In the 1970s, experimental infection of germ-free chickens with avian herpes virus induced pathologic changes resembling those in human CHD (Fabricant, 1978). There have been many studies showing the presence of high titers of antibodies against various organisms in patients with CHD. Although there is always some question about such studies, the incidence is such as to make it appear very likely that antibodies against Helicobacter pylori, Chlamydia pneumonia, Cytomegalovirus, or other herpes viruses are very common in these patients. There is even an association with severe dental carries (Danesh et al., 1997). Stimulated by these reports, there have now been two reports of treatment of patients with CHD with tetracycline derivatives (Gurfinkel et al., 1997; Gupta, et al., 1997). In both studies further complications of CHD were significantly reduced in the treated groups. In one study,
treatment reduced the complications 10-fold (Garfinkel, 1997)."

"...Tetracyclines have now been studied in chondral cell cultures from patients with osteoarthritis and in cell cultures from animals with experimentally produced arthritis. They have been shown to have chondro-protective effects (Amin et al., 1996). NO is spontaneously released from human cartilage affected by osteo- or rheumatoid arthritis in quantities sufficient to cause cartilage damage. In a recent report, tetracyclines have been shown to reduce the expression and function of human osteoarthritis-effected NOS (iNOS) (Amin et al., 1996). It appears that in addition to the antibacterial action of these drugs, tetracyclines inhibit the expression of NOS, leading to reduction in the toxic consequences of production of NO. It is likely that these compounds will be beneficial in the treatment of osteoarthritis, as well as CHD. They will also probably be of therapeutic value in rheumatoid arthritis and cardiomyopathy, both thought to be autoimmune diseases caused largely by excess NO."

"...The current theory of CHD is that it is induced by an elevation of plasma cholesterol above the normal limit of 200 mg%. However, if one looks at the incidence of CHD vs. the concentration of plasma cholesterol, one finds that as cholesterol passes the 200 mg% concentration, there is only a very slight increase in the incidence of the disease as one reaches 250mg% and the slope of the incidence begins to rise between 250 and 300 and rises quite rapidly as one approaches 400 mg%. There are many cases of CHD in patients with perfectly normal cholesterol. Indeed, increased LDL cholesterol has been considered particularly ominous, whereas HDL cholesterol has been thought to be protective. However, in many cases, CHD develops and has its downward progression in the presence of normal cholesterol and other
lipids."

"...The fact that injection of moderate amounts of LPS to mimic the effect of bacterial infection induces increased numbers of IL-1a immunoreactive neurons in the region of the thermosensitive neurons in the preoptic hypothalamic region, plus increased IL-b mRNA and iNOS mRNA in the PVN, AN, median eminence, choroid plexus, meninges, and in massive amounts in the anterior pituitary and pineal with consequent release of NO, suggests that toxic amounts of NO could exist in these regions during moderate infections, even though there is no direct involvement of the brain"

"...Indeed, CNS AIDS has led to Alzheimer-like changes in the brain (Griffin, 1988). Therefore, NO may cause much of the
neuropathologic changes in CNS AIDS."

"...In conclusion, although much work needs to be done, it is already known that treatment of patients with antioxidants, vitamin C and E, which would reduce the toxic effects of NO, is of value in patients with CHD. This is probably the mechanism of their protective effects against CHD. Finally, compounds that inhibit the production of NO directly, such as inhibitors of NOS or agents that inhibit the production of NOS, such as corticoids, the tetracyclines, and a-MSH may prove useful in slowing the aging process. Aspirin blocks cyclooxygenase I, thereby reducing production and toxicity of prostanoids produced by NO, accounting for its protective effect in CHD."


One last point - one of the quotes above talks about how adenosine is one of the most potent stimulators of prolactin. This would suggest that adenosine antagonists like caffeine would be really good for lowering prolactin. I posted some studies several days ago that suggest just that - i.e. caffeine acts as functional dopamine agonist and inhibits prolactin release.

Thoughts?

Wow all my favourite foods contain tryptophan
According to Google:
"Dietary sources. Tryptophan is present in most protein-based foods or dietary proteins. It is particularly plentiful in chocolate, oats, dried dates, milk, yogurt, cottage cheese, red meat, eggs, fish, poultry, sesame, chickpeas, almonds, sunflower seeds, pumpkin seeds, buckwheat, spirulina, and peanuts."

What's left! Probably that's why I have autoimmune disease.

 

[haidut]

Wow all my favourite foods contain tryptophan
According to Google:
"Dietary sources. Tryptophan is present in most protein-based foods or dietary proteins. It is particularly plentiful in chocolate, oats, dried dates, milk, yogurt, cottage cheese, red meat, eggs, fish, poultry, sesame, chickpeas, almonds, sunflower seeds, pumpkin seeds, buckwheat, spirulina, and peanuts."

What's left! Probably that's why I have autoimmune disease.

Adding a bit of gelatin to each meal helps block tryptophan absorption and limit its effects.

 

[ddjd]

Check out perfecthairhealth for more info.
https://perfecthairhealth.com/trans-hormone-replacement-therapy-hair-regrowth/

yeah ive been following rob for years.

 

[Curiousman]

no ones mentioned hair loss in this thread. Could nitric oxide be the primary cause of hair thinning and possibly the starting point for the cascade of other stress hormones and neurotransmitters - cortisol, estrogen, serotonin etc.

I personally think low co2 and high nitric oxide is the key reason for hair loss

Nitric oxide in the human hair follicle: constitutive and dihydrotestosterone-induced nitric oxide synthase expression and NO production in dermal papilla cells.

Abstract
The free radical nitric oxide, generated by different types of epidermal and dermal cells, has been identified as an important mediator in various physiological and pathophysiological processes of the skin, such as regulation of blood flow, melanogenesis, wound healing, and hyperproliferative skin diseases. However, little is known about the role of NO in the human hair follicle and in hair cycling processes. Here we demonstrate for the first time that dermal papilla cells derived from human hair follicles spontaneously produce NO by measuring nitrate and nitrite levels in culture supernatants. This biomolecule is apparently formed by the endothelial isoform of nitric oxide synthase, which was detected at the mRNA and protein levels. Remarkably, basal NO level was enhanced threefold by stimulating dermal papilla cells with 5alpha-dihydrotestosterone (DHT) but not with testosterone. Addition of N-[3-(aminomethyl)benzyl]acetamidine (1400W), a highly selective inhibitor of inducible nitric oxide synthase, restrained the elevation in NO level induced by DHT. Analyses of DHT-stimulated cells at the mRNA and protein levels confirmed the expression of inducible nitric oxide synthase. These findings suggest NO as a signaling molecule in human dermal papilla cells and implicate basal and androgen-mediated NO production to be involved in the regulation of hair follicle activity.

Would it be an excessive production of NO, the cause of hair loss ? It's known that cicle of steroids containing high doses of DHT are the worst for hair loss. Would it be nitric oxide behind it ?

 

[ddjd]

Nitric oxide in the human hair follicle: constitutive and dihydrotestosterone-induced nitric oxide synthase expression and NO production in dermal papilla cells.

Abstract
The free radical nitric oxide, generated by different types of epidermal and dermal cells, has been identified as an important mediator in various physiological and pathophysiological processes of the skin, such as regulation of blood flow, melanogenesis, wound healing, and hyperproliferative skin diseases. However, little is known about the role of NO in the human hair follicle and in hair cycling processes. Here we demonstrate for the first time that dermal papilla cells derived from human hair follicles spontaneously produce NO by measuring nitrate and nitrite levels in culture supernatants. This biomolecule is apparently formed by the endothelial isoform of nitric oxide synthase, which was detected at the mRNA and protein levels. Remarkably, basal NO level was enhanced threefold by stimulating dermal papilla cells with 5alpha-dihydrotestosterone (DHT) but not with testosterone. Addition of N-[3-(aminomethyl)benzyl]acetamidine (1400W), a highly selective inhibitor of inducible nitric oxide synthase, restrained the elevation in NO level induced by DHT. Analyses of DHT-stimulated cells at the mRNA and protein levels confirmed the expression of inducible nitric oxide synthase. These findings suggest NO as a signaling molecule in human dermal papilla cells and implicate basal and androgen-mediated NO production to be involved in the regulation of hair follicle activity.

Would it be an excessive production of NO, the cause of hair loss ? It's known that cicle of steroids containing high doses of DHT are the worst for hair loss. Would it be nitric oxide behind it ?

Interesting. A lot of people in this forum don't believe DHT is the reason for hairloss. People with lots of hair on their heads also have high DHT levels, as well as bald people, so it doesn't quite make sense. But i definitely think overproduction of NO is the most likely cause of hair loss/thinning