7 replies to this topic

[Nate-2004]

As a tangential topic to the discussion in this thread I've become more curious lately about PDE and its association with age. There's not a lot of published articles looking into this but people do know that inhibition of PDE5 (Viagra) makes men like teenagers again when it comes to libido and sexual function. Why? Why do men lose libido as they age? (libido can't just be about neurotransmitters) What does it have to do with PDE? Why is PDE inhibition a big target for treating age related disease? Does PDE increase as we age, as with inflammatory cytokines, CD38, etc?

 

From Wikipedia:

 

[quote]

Methylated xanthines act as both

1. competitive nonselective phosphodiesterase inhibitors,^[5] which raise intracellular cAMP, activate PKA, inhibit TNF-alpha ^[6][7] and leukotriene ^[8] synthesis, and reduce inflammation and innate immunity ^[8] and


2. nonselective adenosine receptor antagonists ^[9]

 

[./quote]

Edited by Nate-2004, 11 January 2018 - 02:59 PM.

[ceridwen]

Can it help women too?

[Nate-2004]

That's what I am wondering. PDE5 inhibition is generally for men and ED (Viagra) but it's been rumored that Viagra also works for women.

[Dorian Grey]

Don't know about PDE5 inhibitors, but I've done a bit of research into xanthines and like them.  Jeanne Calment, the worlds longest lived human (122 years) ate a kilo of chocolate a week (theobromine = xanthine).  

 

http://www.collectiv...e-of-longevity/

 

"Jeanne Calment smoked cigarettes (started at age 21), drank port wine, and ate a couple of pounds of chocolate sweets a week until she was 119 years old."

 

I'm not sure exactly what the protective effect of xanthines is, but I suspect is has something to do with lowering the action of xanthine oxidaise (XO), which causes inflammation in part by releasing free iron from ferritin spiking hydroxyl radical formation, the most destructive form of free radical.  

 

https://www.ncbi.nlm...les/PMC1147813/

 

"Free iron is liable to catalyse the formation of the extremely reactive and damaging OH. radical."

 

One would think the body would respond to increased dietary xanthines by ramping up XO, but apparently this does not occur.  The XO most likely becomes deactivated by xanthines, reducing iron liberation from ferritin.  This might explain the beneficial effects of coffee too (caffeine=xanthine).  

 

More on XO here: http://www.sciencedi...anthine-oxidase

 

It's an interesting angle on possible simple dietary changes that may have big effects on health & longevity.  

Edited by Dorian Grey, 11 January 2018 - 10:03 PM.

[Nate-2004]

I'm talking about all PDE's not just PDE5. The viagra was just an example. I think it's something worth looking into though.

[Dorian Grey]

Xanthines (caffeine and theobromine) are both "nonselective" PDE inhibitors, not just PDE5.  

 

https://en.wikipedia...erase_inhibitor

 

Nonselective PDE inhibitors[edit]

Methylated xanthines and derivatives:^[5]

• caffeine, a minor stimulant
• aminophylline
• IBMX (3-isobutyl-1-methylxanthine), used as investigative tool in pharmacological research
• paraxanthine
• pentoxifylline, a drug that has the potential to enhance circulation and may have applicability in treatment of diabetes, fibrotic disorders, peripheral nerve damage, and microvascular injuries ^[6]
• theobromine
• theophylline, a bronchodilator

Methylated xanthines act as both

1. competitive nonselective phosphodiesterase inhibitors,^[5] which raise intracellular cAMP, activate PKA, inhibit TNF-alpha ^[6][7] and leukotriene ^[8] synthesis, and reduce inflammation and innate immunity ^[8] and
2. nonselective adenosine receptor antagonists ^[9]

But different analogues show varying potency at the numerous subtypes,

 

-----------------------

 

Thought this was what you were looking at.  

[HighDesertWizard]

"Jeanne Calment smoked cigarettes (started at age 21), drank port wine, and ate a couple of pounds of chocolate sweets a week until she was 119 years old."

 

<... snip ... >

 

I'm not sure exactly what the protective effect of xanthines is, but I suspect is has something to do with lowering the action of xanthine oxidaise (XO), which causes inflammation in part by releasing free iron from ferritin spiking hydroxyl radical formation, the most destructive form of free radical.  

 

<... snip ... >

 

 

 

Tyrosol and hydroxytyrosol, two main components of olive oil, protect N2a cells against amyloid-β-induced toxicity. Involvement of the NF-κB signaling

 

 

Xanthine oxidase-induced oxidative stress causes activation of NF-kappaB and inflammation in the liver of type I diabetic rats

[Believer]

Can it help women too?

Serotonin agonists already do. Women also have free access to estrogen and progesterone which not only fully restores libido but increases it above baseline. Not only that but estrogen and progesterone have anti-aging effects that extend to pretty much every facet of the aging process, from curing atherosclerosis and preventing it to improving skin quality to improving cognitive function and the list goes on and on.