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Old human cells rejuvenated in breakthrough discovery on ageing

senescent cells rejuvenation

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#121 Rocket

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Posted 27 December 2017 - 12:41 PM

 

I don't quite understand what you're trying to achieve with that combo.

 

The resveratrol to rescue and rejuvenate senescent cells, and the quercetin and dasatinib to induce apoptosis in senescent cells?  

 

Would seem to be at cross purposes.

 

The thought crossed my mind but Q goes well with R in that it will inhibit the P450 enzymes that metabolize R. Yes, part of the goal is to help R rescue senescent cells, but I don't think that necessarily means D+Q's induction of apoptosis in senescent cells is necessarily going to prevent the former.

 

Also, it'd been 6 months since my last round of D+Q, I figured I would do it differently this time, with the sublingual ethanol solution.

 

Rocket's idea above might be a better idea, but there's no evidence for or against doing it all at the same time.

 

 

I'm going to do a "blast" of D+Q for 2 days to kill off S-cells. Then a few days later start with the l-R+C to rejuvenate the S-cells that weren't wiped out by D+Q. But like on the bodybuilding forums, this is all bro science so who really knows. . . . .

 

 



#122 Nuke

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Posted 27 December 2017 - 01:42 PM

Being interested in PDE inhibitors, I read this study a few days ago.  While the article in the first post does not state it, it would not surprise me if the effect on splicing factors are also cAMP mediated. If so, there are many other, far more bioavailable options out there. 

 

A quick google found this, that seems to support the idea.  

 

My aim reading up on PDE inhibitors in currently a bit different, but if this is a possible added bonus, I won't complain. If I find anything more related to this, I'll post it. Unfortunately PDE and cAMP is a pretty complicated topic, so it may take a while.

 

 


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#123 Rocket

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Posted 27 December 2017 - 04:31 PM

Being interested in PDE inhibitors, I read this study a few days ago.  While the article in the first post does not state it, it would not surprise me if the effect on splicing factors are also cAMP mediated. If so, there are many other, far more bioavailable options out there. 

 

A quick google found this, that seems to support the idea.  

 

My aim reading up on PDE inhibitors in currently a bit different, but if this is a possible added bonus, I won't complain. If I find anything more related to this, I'll post it. Unfortunately PDE and cAMP is a pretty complicated topic, so it may take a while.

 

Does this mean we'll be getting erections all the time? I can't really read these detailed studies but if it's effecting PDE5, then....?


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#124 Nate-2004

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Posted 27 December 2017 - 06:22 PM

So Viagra basically: "Part of the physiological process of erection involves the release of nitric oxide (NO) in vasculature of the corpus cavernosum as a result of sexual stimulation. NO activates the enzyme guanylate cyclase which results in increased levels of cyclic guanosine monophosphate (cGMP), leading to smooth muscle relaxation in blood vessels supplying the corpus cavernosum, resulting in increased blood flow and an erection.

PDE5 inhibitors inhibit the degradation of cGMP by PDE5, increasing bloodflow to the penis during sexual stimulation. This mode of action means that PDE5 inhibitors are ineffective without sexual stimulation."



#125 Nuke

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Posted 27 December 2017 - 06:59 PM

Hi Rocket

 

Resveratrol seems to have no affinity for PDE5A, so sadly no erections. It does inhibit PDE1, 3 and 4 though. Rolipram mostly inhibits PDE4B and PDE4D (but the other PDE4 isoforms too). PDE4 inhibitors are not that hard to get, unfortunately they have the common side effect of nausea. That we can blame on PDE4D inhibition. Ibudilast and Roflumilast are both possibilities that comes to mind, but Ibudilast looks far more favorable. They have just finished testing it over 2 years at 60-100mg/day for MS in a phase 2 trail. https://www.medscape...warticle/887774

 

PDE5 inhibitors I find interesting for other reasons too. It may just increase both healthspan and cognition via other pathways. But as I said, I have much more to learn on this topic.


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#126 Rocket

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Posted 30 December 2017 - 01:50 AM

Good stuff, Nuke.

Well my order came this afternoon and my experiment is underway. I only got in 375mg of R because of the time. It looks like it has to be kept refrigerated which will make it difficult to dose during business hours... The bottle is huge and this will last a very long time.

Edited by Rocket, 30 December 2017 - 01:52 AM.


#127 recon

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Posted 30 December 2017 - 04:26 PM

There seems to be some negative effects of high resveratrol doses such as increased LDL and the sorts. Have to check back the literature for the list of negative effects of high dosing.

Then if you self-experimenters will take consistent blood checkups throughout this experiment we can search for those negative effects as “biomarkers” that we can use evaluate whether to lower the dosage. That way we can, in a way, evaluate the actual dosage that subsist in the bloodstream.
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#128 Rocket

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Posted 30 December 2017 - 06:35 PM

There seems to be some negative effects of high resveratrol doses such as increased LDL and the sorts. Have to check back the literature for the list of negative effects of high dosing.

Then if you self-experimenters will take consistent blood checkups throughout this experiment we can search for those negative effects as “biomarkers” that we can use evaluate whether to lower the dosage. That way we can, in a way, evaluate the actual dosage that subsist in the bloodstream.

 

I have read the opposite, that R decreases low density lipoprotein.



#129 DrowArcher

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Posted 31 December 2017 - 03:08 PM

Hm, anyone came across any articles linking resveratrol to epigenetics? As I found on the bodybuilding forums, some folks talk about losing long-term muscle adaptations after injecting resveratrol. Again, if my understanding is correct, these are stored epigenetically. What I can't piece together, is that if it's dna methylation - why don't the cells revert all the way back to plurepotency.



#130 greenwich

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Posted 31 December 2017 - 11:57 PM

After you guys get done with 10 of those all-day resveratrol blasts, I'll be interested to hear if you have any palpable improvements in health or vitality -- 



#131 Rocket

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Posted 01 January 2018 - 01:14 AM

I definitely have some good anti-inflammatory effects that were noticeable after the first day.



#132 Nate-2004

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Posted 01 January 2018 - 06:49 PM

Considerable and lasting positive differences in skin and energy for sure so far. Like maybe 15-20% difference.


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#133 Rocket

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Posted 01 January 2018 - 07:53 PM

I've been megadosing since my product was delivered. I have noticed energy improvements as well but that seems like it could be placebo so I didn't report that. I'm glad that someone else posted that they noticed that too. I'm going to hold off on skin comments.



#134 Oakman

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Posted 03 January 2018 - 01:24 AM

As a placeholder, 12/30 & 1/1 I completed my 36 hr protocol with a total of  900 mg R (sublingual, micronized, liosomal), 311 mg Curcumin, 150 mg Forskolin, 10 grams D-Ribose. After 4 wks of 1/wkly dosing, I'll be able to report any noticeable effects with more confidence.



#135 Rocket

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Posted 03 January 2018 - 01:55 AM

What are all those supps for? You took that once weekly?

#136 Oakman

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Posted 03 January 2018 - 03:01 AM

What are all those supps for? You took that once weekly?

 

D-Ribose & Curcumin for R solubility & bioavailability, Forskolin to raise cAMP levels, D-Ribose for RNA. Taken over a 24 hr period (effective ~36 hrs), once each week.



#137 RIURAO

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Posted 03 January 2018 - 01:32 PM

 

What are all those supps for? You took that once weekly?

 

D-Ribose & Curcumin for R solubility & bioavailability, Forskolin to raise cAMP levels, D-Ribose for RNA. Taken over a 24 hr period (effective ~36 hrs), once each week.

 

What kind exactly of Curcumin are you using? . D-Ribose you are using, is only for recovery after workouts, or does it have any other purpose?



#138 Nate-2004

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Posted 03 January 2018 - 03:42 PM

If R is soluble in alcohols like ethanol, DMSO and methanol, I wonder how soluble it is in something like EVOO.



#139 Oakman

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Posted 03 January 2018 - 04:08 PM

 

 

What are all those supps for? You took that once weekly?

 

D-Ribose & Curcumin for R solubility & bioavailability, Forskolin to raise cAMP levels, D-Ribose for RNA. Taken over a 24 hr period (effective ~36 hrs), once each week.

 

What kind exactly of Curcumin are you using? . D-Ribose you are using, is only for recovery after workouts, or does it have any other purpose?

 

Curcumin

    UltraCUR - a protein bound curcumin for improved absorption

    Liposomal Curcumin - with liposomal resveratrol to enhance absorption (see graphs in an earlier post)

D-Ribose - use as a solution for Micronized trans-Resveratrol to enhance solubility, which is virtually nonexistent for H20 and R

    "Solubility of tRES in water and across the 2.0M concentrations of the dextrose, fructose, Ribose, sucrose, and Xylitol solutions are presented in TABLE 1. The solubility of tRES was significantly enhanced in the 2.0M ribose solution (p = 0.0013), but not in fructose (p = 0.0950), dextrose (p = 0.2284), sucrose (p = 0.5824), or xylitol (p = 0.3330)."

D-Ribose - while increasing R solubility, "The ribose β-D-ribofuranose (59% of D-Ribose) forms part of the backbone of RNA. It is related to deoxyribose, which is found in DNAPhosphorylated derivatives of ribose such as ATP and NADH play central roles in metabolismcAMP and cGMP, formed from ATP and GTP, serve as secondary messengers in some signalling pathways."


Edited by Oakman, 03 January 2018 - 04:10 PM.

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#140 Rocket

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Posted 04 January 2018 - 04:07 PM

I will say again that the anti-inflammatory properties are amazing when mega-dosing. For about the last 6 weeks I have had a case of mild carpal tunnel in one of my wrists. Since starting on the l-R + l-C the carpal tunnel is 98% gone. Prescription oral steroids didn't do a thing for my condition... But the over the counter liposomal formulation of L+C has beaten established medical science!

 

One disturbing thing is that I have lost some weight. I lift weights, which means my goal is to put weight on, not  get skinnier. I am down about 2 pounds since starting this 4 or 5 days ago. I lifted weights yesterday and didn't feel like I have lost strength, but definitely I have lost body mass.

 

My dose is running around 0.7g/day of the l-R (the l-C is WAY higher) taken in doses in the morning, afternoon, and night.


Edited by Rocket, 04 January 2018 - 04:13 PM.

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#141 mikela

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Posted 04 January 2018 - 07:37 PM

I will say again that the anti-inflammatory properties are amazing when mega-dosing. For about the last 6 weeks I have had a case of mild carpal tunnel in one of my wrists. Since starting on the l-R + l-C the carpal tunnel is 98% gone. Prescription oral steroids didn't do a thing for my condition... But the over the counter liposomal formulation of L+C has beaten established medical science!

 

One disturbing thing is that I have lost some weight. I lift weights, which means my goal is to put weight on, not  get skinnier. I am down about 2 pounds since starting this 4 or 5 days ago. I lifted weights yesterday and didn't feel like I have lost strength, but definitely I have lost body mass.

 

My dose is running around 0.7g/day of the l-R (the l-C is WAY higher) taken in doses in the morning, afternoon, and night.

 

Which formulation are you using?



#142 Rocket

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Posted 04 January 2018 - 08:42 PM

I'll let you know when I get back home. I bought a very large bottle thinking that it would last me about a month.... Nope! 5 days in and it's half gone. I take about 12 doses each day (I would love to take 20 each day) . So far I am loving this stuff. Aches and pains are disappearing and I have more energy and I am not sure but my skin looks brighter and healthier to me.

 

I hope this weight loss stops or else I'll go back onto PEDs to regain.


Edited by Rocket, 04 January 2018 - 08:43 PM.

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#143 rarefried

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Posted 04 January 2018 - 09:12 PM

I'll let you know when I get back home. I bought a very large bottle thinking that it would last me about a month.... Nope! 5 days in and it's half gone. I take about 12 doses each day (I would love to take 20 each day) . So far I am loving this stuff. Aches and pains are disappearing and I have more energy and I am not sure but my skin looks brighter and healthier to me.

 

I hope this weight loss stops or else I'll go back onto PEDs to regain.

With the addition to my supplement regime of .75g/day of R (mostly powder from Mega Resveratrol;  I was taking Curcumin already at the time without knowing it might enhance the bioavailability of R) and without any changes in my diet I lost about 10 pounds over the course of several months.  The weight loss stopped there for me.  I wasn't concerned about it because at the time I attributed it to working out more frequently because of quicker recovery time between workouts.  However, I haven't gained any of it back, even during relatively sedentary spells when I haven't reduced calorie intake.  In fact, not only did the weight loss not concern me, but I took this as evidence that the R I was taking was 'bioavailable' as opposed to causing a beneficial placebo effect.  I was about 45 years old when I started, I'm 53 now, have increased my dosage just slightly, and the situation is the same.  My brother introduced .5g R (and C) to his supplements about a year ago and lost about the same amount of weight over roughly the same period of time (again without making any other changes to diet or supplement intake other than those two) and stopped there.  



#144 Jon-a-thon

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Posted 06 January 2018 - 11:32 PM

Hey folks. I'm new here. I too have been interested in resveratrol since this study came out. It seems perfectly logical that sublingual R dosed throughout the day could potentially be the key (short of blocking the liver enzymes or doing an IV infusion). If it doesn't work, I'm not sure why. We know that sublingual resveratrol delivers a higher concentration of R to the bloodstream faster based on the ribose lozenge study. We know that the liver doesn't get a chance to kill it all immediately when given by sublingual. We know that 24h exposure to R rejuvenates human cells based on the original study in this thread. Is anyone trying the continuous sublingual approach right now and if so, what are you seeing?!

#145 Rocket

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Posted 07 January 2018 - 02:06 AM

Hey folks. I'm new here. I too have been interested in resveratrol since this study came out. It seems perfectly logical that sublingual R dosed throughout the day could potentially be the key (short of blocking the liver enzymes or doing an IV infusion). If it doesn't work, I'm not sure why. We know that sublingual resveratrol delivers a higher concentration of R to the bloodstream faster based on the ribose lozenge study. We know that the liver doesn't get a chance to kill it all immediately when given by sublingual. We know that 24h exposure to R rejuvenates human cells based on the original study in this thread. Is anyone trying the continuous sublingual approach right now and if so, what are you seeing?!

Megadosing l-R with curcumin for a week now. FANTASTIC anti inflammatory results! I don't know about rejuvenation... Blood tests coming very soon. My skin looks brighter for lack of a more descriptive word. If the area under my eyes could improve I could pass for many years younger. I am about the same age as Nate. I use minoxidil which I understand affects the under eye area... Who knows! This stuff ain't cheap so I can't run it 365 a year. But yeah I can tell something positive is happening.

Can't wait for longer term results. I will be doing the foxo4 peptides once I get in on a group buy to mop up whatever cells aren't responding to the l-R.

Edited by Rocket, 07 January 2018 - 02:08 AM.

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#146 Nate-2004

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Posted 07 January 2018 - 03:42 PM

Just be sure to avoid sulforaphane (broccoli sprouts) or broccomax or anything of the sort on these R days. It significantly boosts the very enzymes we're trying to inhibit.


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#147 Rocket

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Posted 07 January 2018 - 09:25 PM

That's my favorite veggie. Good to know

 

My large bottle of l-R+C runs out tomorrow. Wow, that stuff goes fast when megadosing. It's been so very worth it however, just for what it did to my mild carpal tunnel syndrome which is now totally gone after about 7 weeks of conservative treatment that did nothing.


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#148 Rocket

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Posted 08 January 2018 - 02:36 AM

I ordered from a new supplier that I found that offers pure liposomal R at 120mg per dose with 96 doses per bottle. I am definitely going to keep this trial going for at least about another week. The inflammation effect has been amazing, so I don't know if that was the R or the C. Energy levels are better. Every time I shave, I think my skin looks different. That could be placebo but who knows. I have increased calories with a small protein meal with fruit for carbs before bed to stop the weight loss I saw. Its no secret that I have a bad back injury going on for over 15 years and I am a hobbyist weight lifter. So my back normally feels "creaky" throwing around weights... My back feels noticeably better since starting this experiment. Must be inflammation reductions. I also hit a PR benching 275 this week. I don't think l-R is anabolic but the good news is that it doesn't negatively affect muscle as I feared. I haven't had time to do pure cardio to see if that is improved at all.

I have ordered full blood tests to see what's going on with lipids, liver, kidneys, and thyroid and hormones.

One other thing that worried me was i was experiencing itchy nipples for the first few days. Like a steroid cycle without appropriate anti estrogen meds. I started taking some leftovers of arimidex that I have. It couldn't be prolactin because I normally run a little pramipexole at night for dopamine reasons.

Edited by Rocket, 08 January 2018 - 02:46 AM.

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#149 Oakman

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Posted 26 January 2018 - 06:50 PM

As a placeholder, 12/30 & 1/1 I completed my 36 hr protocol with a total of  900 mg R (sublingual, micronized, liosomal), 311 mg Curcumin, 150 mg Forskolin, 10 grams D-Ribose. After 4 wks of 1/wkly dosing, I'll be able to report any noticeable effects with more confidence.

 

Four weeks in, here's what I've experienced as taken from the log I kept. Although I normally take multiple supplements daily, on days dosing R+C I stopped all except melatonin and NR.

 

End 1/1/18  Took 36 hr protocol (as above) Sunday/Monday. Felt invincible 1/1 (meaning I felt strong, positive, mentally sharp).

 

End 1/7/18  Increased to 48 hr full 2 day protocol. Increased R+C totals to 1725mg R + 622mg C. Felt a little nausea at end. Slept next day until noon. By Thursday (1/11) felt really good and invincible. Gym was done at 10% higher level/weight.

 

End 1/14/18  This week I mixed the micronized Resveratrol and D-Ribose with a couple ounces OJ, Brain Fuel (1 tsp), soy lecithin (¼ tsp), 10 g whey concentrate. After power mixing, add liposomal R-C, stir. Feeling foggy and tired Mon/Tue, by Wednesday (1/17), that invincible feeling has come on again.

 

End 1/21/18  After 36 hrs I got a small background headache, so I stopped dosing after Sunday morning. Headache stayed until Thursday afternoon (1/25), plus I did a lot of napping thru Thursday. Friday I feel great.

 

At this point I'm taking a break to see what effects are long term. Although I felt almost nothing different while taking R+C each time, later tiredness predominated, followed days later by a sense of well being and strength. For the purported in-body processes to produce effects, these time-delayed results seem to make sense. But there also indicate a limit to what can be done repeatedly.

 

But was this the rejuvenation depicted in the original study?  Perhaps, but without blood work, I don't even know what serum levels of R+C may have been, so I have only anecdotal experience to gauge results by. Ideally, my telomeres are lengthened, some genes are reactivated, and some inactive senescence cells have new life.  However, with this level of overdosing, cycling seems wise.  Next time I try this protocol I'll likely decrease dosing see if I can limit the side effects. But overall, I feel it was worthwhile.



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#150 Nate-2004

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Posted 26 January 2018 - 07:34 PM

I would probably stick with that first protocol of 36 hrs with 900mg. I am only going once a week since any more than that seems too much. I feel great with the once a week. The only time I'm getting any D-Ribose is with NAM before workouts.







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