The Nitric Oxide (NO) Theory Of Aging

benaoao

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it's the DHT causing hair loss via its metabolite 3alpha diol

like I posted elsewhere today, the problem is the metabolism of DHT in 3alpha instead of 3beta diol predominantly. NO is androgen-mediated, as said in your quote. No "pre-procarcinogen" (or dedifferentiating) DHT no problem.

People who "don't believe in DHT = hair loss" only miss one step in DHT metabolism.

DHT makes more 3beta diol in healthy thyroid subjects, which is anti inflammatory and differentiating (= no hair loss)

explained here in detail: The Anticancer Testosterone Metabolite 3β-Adiol - Meridian Valley Lab
 

Curiousman

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Ascorbate stimulates endothelial nitric oxide synthase enzyme activity by rapid modulation of its phosphorylation status

Abstract
Long-term exposure to ascorbate is known to enhance endothelial nitric oxide synthase (eNOS) activity by stabilizing the eNOS cofactor tetrahydrobiopterin (BH4). We investigated acute effects of ascorbate on eNOS function in primary (HUVEC) and immortalized human endothelial cells (EA.hy926), aiming to provide a molecular explanation for the rapid vasodilatation seen in vivo upon administration of ascorbate. Enzymatic activity of eNOS and intracellular BH4 levels were assessed by means of an arginine–citrulline conversion assay and HPLC analysis, respectively. Over a period of 4 h, ascorbate steadily increased eNOS activity, although endothelial BH4 levels remained unchanged compared to untreated control cells. Immunoblot analyses revealed that as early as 5 min after treatment ascorbate dose-dependently increased phosphorylation at eNOS-Ser1177 and concomitantly decreased phosphorylation at eNOS-Thr495, a phosphorylation pattern indicative of increased eNOS activity. By employing pharmacological inhibitors, siRNA-mediated knockdown approaches, and overexpression of the catalytic subunit of protein phosphatase 2A (PP2A), we show that this effect was at least partly owing to reduction of PP2A activity and subsequent activation of AMP-activated kinase. In this report, we unravel a novel mechanism for how ascorbate rapidly activates eNOS independent of its effects on BH4 stabilization.
 

ddjd

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Ascorbate stimulates endothelial nitric oxide synthase enzyme activity by rapid modulation of its phosphorylation status

Abstract
Long-term exposure to ascorbate is known to enhance endothelial nitric oxide synthase (eNOS) activity by stabilizing the eNOS cofactor tetrahydrobiopterin (BH4). We investigated acute effects of ascorbate on eNOS function in primary (HUVEC) and immortalized human endothelial cells (EA.hy926), aiming to provide a molecular explanation for the rapid vasodilatation seen in vivo upon administration of ascorbate. Enzymatic activity of eNOS and intracellular BH4 levels were assessed by means of an arginine–citrulline conversion assay and HPLC analysis, respectively. Over a period of 4 h, ascorbate steadily increased eNOS activity, although endothelial BH4 levels remained unchanged compared to untreated control cells. Immunoblot analyses revealed that as early as 5 min after treatment ascorbate dose-dependently increased phosphorylation at eNOS-Ser1177 and concomitantly decreased phosphorylation at eNOS-Thr495, a phosphorylation pattern indicative of increased eNOS activity. By employing pharmacological inhibitors, siRNA-mediated knockdown approaches, and overexpression of the catalytic subunit of protein phosphatase 2A (PP2A), we show that this effect was at least partly owing to reduction of PP2A activity and subsequent activation of AMP-activated kinase. In this report, we unravel a novel mechanism for how ascorbate rapidly activates eNOS independent of its effects on BH4 stabilization.
Are you suggesting eNOS is good?
 

ddjd

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it's the DHT causing hair loss via its metabolite 3alpha diol

like I posted elsewhere today, the problem is the metabolism of DHT in 3alpha instead of 3beta diol predominantly. NO is androgen-mediated, as said in your quote. No "pre-procarcinogen" (or dedifferentiating) DHT no problem.

People who "don't believe in DHT = hair loss" only miss one step in DHT metabolism.

DHT makes more 3beta diol in healthy thyroid subjects, which is anti inflammatory and differentiating (= no hair loss)

explained here in detail: The Anticancer Testosterone Metabolite 3β-Adiol - Meridian Valley Lab
I asked danny roddy about this, he said

"It would be interesting to see if that person had more evidence to support what they were saying in relation to baldness (i.e., 3a-Adiol being higher in baldness)."
 

benaoao

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That’s a tough question, the article above precisely says there’s a lack of testing available for those testosterone metabolites

I’m sure Danny Roddy knows about the enzymes implied in DHT conversion in to 3B diol, and what impacts their activity:
- I’ve seen 3 variants of the HSD enzyme being involved
- I’ve seen a hypothyroid slowing the enzymes activity, as well as strong androgens
- conversely coconut oil, olive oil, zinc and t3 increase the enzymes activity thus DHT is converted into more 3B diol

So hypothyroidism/deficiencies or strong androgens would mean an unfavorable ratio of (3aDiol+DHT)/3bDiol. I’ll look up “hypothyroid” and “3a/3B diol” ratios... may yield more results than baldness

I’m only rephrasing the article though. I think if someone like Roddy could read it up fully and think it through that’d be interesting for his work.
 
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ddjd

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ddjd

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it's the DHT causing hair loss via its metabolite 3alpha diol

like I posted elsewhere today, the problem is the metabolism of DHT in 3alpha instead of 3beta diol predominantly. NO is androgen-mediated, as said in your quote. No "pre-procarcinogen" (or dedifferentiating) DHT no problem.

People who "don't believe in DHT = hair loss" only miss one step in DHT metabolism.

DHT makes more 3beta diol in healthy thyroid subjects, which is anti inflammatory and differentiating (= no hair loss)

explained here in detail: The Anticancer Testosterone Metabolite 3β-Adiol - Meridian Valley Lab
so 3beta diol is good? and just 3alpha causes HL?
 

revenant

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This is pretty confusing... so if increased NO is bad, why do so many things that increase NO seem to be good for longevity/aging in studies? For example l-arginine and aspirin, even vitamin D. Also, NO decreases with aging.

Are there any libido enhancers that *don't* rely on increased NO? It seems that anything that actually works increases NO one way or another.
 

Orangeyouglad

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it's the DHT causing hair loss via its metabolite 3alpha diol

like I posted elsewhere today, the problem is the metabolism of DHT in 3alpha instead of 3beta diol predominantly. NO is androgen-mediated, as said in your quote. No "pre-procarcinogen" (or dedifferentiating) DHT no problem.

People who "don't believe in DHT = hair loss" only miss one step in DHT metabolism.

DHT makes more 3beta diol in healthy thyroid subjects, which is anti inflammatory and differentiating (= no hair loss)

explained here in detail: The Anticancer Testosterone Metabolite 3β-Adiol - Meridian Valley Lab

So dHT to 3a-adiol and 3β-adiol. 3a is gets converted largely back into DHT and is responsible for body hair, acne, and I would imagine, hair loss. 3b is anti-cancer, anti-inflammatory and has no androgenic effects. We shouldn't be trying to block DHT, we should be trying to figure out how to funnel it all into 3β-adiol.

How can we funnel DHT into 3β rather than 3a?
 

Jam

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So dHT to 3a-adiol and 3β-adiol. 3a is gets converted largely back into DHT and is responsible for body hair, acne, and I would imagine, hair loss. 3b is anti-cancer, anti-inflammatory and has no androgenic effects. We shouldn't be trying to block DHT, we should be trying to figure out how to funnel it all into 3β-adiol.

How can we funnel DHT into 3β rather than 3a?

The anticancer testosterone metabolite 3[beta] - Adiol.

Fortunately, researchers are reporting possibilities for stimulating the natural endogenous biosynthesis of 3 [beta] -Adiol with natural substances which stimulate 3 [beta] -HSD and/or 17 [beta] -HSD, the enzymes that convert 5 [alpha] -DHT into 3 [beta] -Adiol. But there's a caution: Although these studies are theoretically promising, none of them have as yet actually measured "before and after" quantities of 3 [beta] -Adiol itself, but rather activity and/or quantity of the enzymes that "lead to" 3 [beta] -Adiol. Until this research has been done, the best alternative is measuring the "before and after" levels in individuals, especially individuals found to personally have low 3 [beta] -Adiol levels. (In my own practice, I've observed that several of the items below have been associated with improved 3 [beta] -Adiol levels in individuals, but it's too early to report that any one is reliably associated with improvement in low 3 [beta] -Adiol levels.)

Let's start with (no kidding) coconut oil and olive oil. In 2008 and 2009, researchers reported that these two oils, used separately, significantly stimulated the activity of 3 [beta] -HSD and 17 [beta] -HSD, as well as significantly raising testosterone levels in experimental animals, while grapeseed oil and soy oil did not have any significant effect. (15), (16)

Then there's our old "male health" standby, zinc. Studies in male rats demonstrated that zinc deficiency decreased 3 [beta] -HSD activity. Zinc deficiency also was associated with a very significant reduction in testosterone itself. (17)

Hypothyroidism and "subclinical" hypothyroidism are relatively common. Here's another reason to be ever-vigilant for these problems: T3 stimulates 3 [beta] -HSD type 2. (18) Although this might suggest that T3 may stimulate 3 [beta] -Adiol, there are as yet no publications exploring this possibility. However, it's easy enough to check in any one individual with lower than desirable 3 [beta] -Adiol.

3 [beta] -HSD also requires NAD (niacinamide adenine dinucleotide), but once again there are no studies yet linking NADH supplementation with improved levels of 3 [beta] -Adiol. (19)

In a study of adrenal cell activity, lithium was reported to increase synthesis of 3p-HSD type 2. (Obviously the adrenals and testes are entirely different, but the 3 [beta] -HSD enzyme is the same enzyme in both areas).

Lastly (for now) all-trans retinoic acid (ATRA) has been shown to increase 3 [beta] -HSD type 2. (20) As too much ATRA can become toxic, this one is available only by prescription.
 
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Orangeyouglad

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Thanks for posting @Jam. I read this one already. I can’t remember if it’s later in this article or another one on the same site, but they essentially say that everything listed that works to stimulate 3b also stimulate 3a. If I remember correctly @haidut posted something awhile back saying that it was hard to target a single metabolite.

The anticancer testosterone metabolite 3[beta] - Adiol.

Fortunately, researchers are reporting possibilities for stimulating the natural endogenous biosynthesis of 3 [beta] -Adiol with natural substances which stimulate 3 [beta] -HSD and/or 17 [beta] -HSD, the enzymes that convert 5 [alpha] -DHT into 3 [beta] -Adiol. But there's a caution: Although these studies are theoretically promising, none of them have as yet actually measured "before and after" quantities of 3 [beta] -Adiol itself, but rather activity and/or quantity of the enzymes that "lead to" 3 [beta] -Adiol. Until this research has been done, the best alternative is measuring the "before and after" levels in individuals, especially individuals found to personally have low 3 [beta] -Adiol levels. (In my own practice, I've observed that several of the items below have been associated with improved 3 [beta] -Adiol levels in individuals, but it's too early to report that any one is reliably associated with improvement in low 3 [beta] -Adiol levels.)

Let's start with (no kidding) coconut oil and olive oil. In 2008 and 2009, researchers reported that these two oils, used separately, significantly stimulated the activity of 3 [beta] -HSD and 17 [beta] -HSD, as well as significantly raising testosterone levels in experimental animals, while grapeseed oil and soy oil did not have any significant effect. (15), (16)

Then there's our old "male health" standby, zinc. Studies in male rats demonstrated that zinc deficiency decreased 3 [beta] -HSD activity. Zinc deficiency also was associated with a very significant reduction in testosterone itself. (17)

Hypothyroidism and "subclinical" hypothyroidism are relatively common. Here's another reason to be ever-vigilant for these problems: T3 stimulates 3 [beta] -HSD type 2. (18) Although this might suggest that T3 may stimulate 3 [beta] -Adiol, there are as yet no publications exploring this possibility. However, it's easy enough to check in any one individual with lower than desirable 3 [beta] -Adiol.

3 [beta] -HSD also requires NAD (niacinamide adenine dinucleotide), but once again there are no studies yet linking NADH supplementation with improved levels of 3 [beta] -Adiol. (19)

In a study of adrenal cell activity, lithium was reported to increase synthesis of 3p-HSD type 2. (Obviously the adrenals and testes are entirely different, but the 3 [beta] -HSD enzyme is the same enzyme in both areas).

Lastly (for now) all-trans retinoic acid (ATRA) has been shown to increase 3 [beta] -HSD type 2. (20) As too much ATRA can become toxic, this one is available only by prescription.
 

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