LONGECITY

Hsu SC et al., Resveratrol increases anti-aging Klotho gene expression via the activating transcription factor 3/c-Jun complex-mediated signaling pathway, Int J Biochem Cell Biol. 2014 Jun 6.

 

Abstract

 

The Klotho gene functions as an aging suppressor gene. Evidence from animal models suggests that induction of Klotho expression may be a potential treatment for age-associated diseases. However, the molecular mechanism involved in regulating renal Klotho gene expression remains unclear. In this study, we determined that resveratrol, a natural polyphenol, induced renal Klotho expression both in vivo and in vitro. In the mouse kidney, resveratrol administration markedly increased both Klotho mRNA and protein expression. In resveratrol-treated NRK-52E cells, increased Klotho expression was accompanied by the upregulation and nuclear translocation of activating transcription factor 3 (ATF3) and c-Jun. ATF3 or c-Jun overexpression enhanced the transcriptional activation of Klotho. Conversely, resveratrol-induced Klotho expression was attenuated in the presence of dominant-negative ATF3 or c-Jun. Coimmunoprecipitation and a chromatin immunoprecipitation assay revealed that ATF3 physically interacted with c-Jun and that the ATF3/c-Jun complex directly bound to the Klotho promoter through ATF3- and AP-1-binding elements. c-Jun cotransfection augmented the effects of ATF3 on Klotho transcription in vitro. Although Sirtuin 1 mRNA expression was induced by resveratrol and involved in regulating Klotho mRNA expression, it was not the primary cause for the aforementioned ATF3/c-Jun pathway. In summary, resveratrol enhances the renal expression of the anti-aging Klotho gene, and the transcriptional factors ATF3 and c-Jun functionally interact and coordinately regulate the resveratrol-mediated transcriptional activation of Klotho. Copyright © 2014. Published by Elsevier Ltd.

FULL TEXT:  Resveratrol increases anti-aging Klotho gene expression via the activating transcription factor 3/c-Jun complex-mediated signaling pathway

FULL TEXT:  Resveratrol increases anti-aging Klotho gene expression via the activating transcription factor 3/c-Jun complex-mediated signaling pathway

 

Do you have any up-to-date formulation/brand recommendations? 

Currently I am using RevGenetics Nitro 250 Micronized Resveratrol one cap upon rising.

 klotho-res.png   95.71KB   1 downloads

 

Cells (renal epithelial, rat) were treated to

1) 2.5, 5, 10, 20 or 40 uM resveratrol for a 24-hour period, or

2) 40 uM resveratrol for a duration of 0, 3, 6, 12 or 24 hours

 

Can the above can be achieved in a person taking a resveratrol supplement?

 

A user called Jz99 posted something interesting about this on .anti-agingfirewalls.com - 

 

"To add to the complexity of the resveratrol picture as an anti-oxidant: It’s now implicated in increasing klotho levels in the kidney.

 

Edited by Phoenicis, 23 June 2014 - 02:34 PM.

A recent study was published where subjects took 10,000 IU of Vitamin D3 daily and it upregulated Klotho expression.  Unfortunately I'm not allowed to post links yet.  You can search for the study.

this? http://www.nature.co...ki2012338a.html

 

I wonder how safe 10,000iu Calcitriol / day is?

I have heard of experiments where human parkinson subjects received up towards 125.000 IE vitamin D3/day with no toxicity. It seems well tolerated.

Edited by Cosmicalstorm, 11 July 2014 - 08:42 AM.

Here is an interesting review on the roll of Klotho in aging and it's mediation with exercise.
" Skeletal muscle as a regulator of the longevity protein, Klotho "

http://www.ncbi.nlm....56/#!po=51.9231

Surely 5,000 iu mediate Klotho as well then? I could not tell from the vague results in that study.

A recent study was published where subjects took 10,000 IU of Vitamin D3 daily and it upregulated Klotho expression.  Unfortunately I'm not allowed to post links yet.  You can search for the study.

 

 

this? http://www.nature.co...ki2012338a.html

 

I wonder how safe 10,000iu Calcitriol / day is?

 

that's not the study.  this is it here: http://online.lieber...4.5238.abstract

 

For dosage safety, I love mayo clinic's feature where it harvests historical dosages used in published research studies (as well as which ailment was being treated), so you can get a rough idea as to risk:benefits safety in dosing.  In the case of vitamin D3, here's the link for that: http://www.mayoclini...ng/hrb-20060400

Surely 5,000 iu mediate Klotho as well then? I could not tell from the vague results in that study.

 

yes I personally advocate 5,000 IU daily unless one is an outdoors person where one gets enough sun, in which case one should only take 1,000 IU daily.  the body can biosynth surprisingly large amounts of vitamin D3 upon exposure to UV rays.  but yeah people who stay indoors all the time should go for 5,000 IU daily.  it's pretty safe because the liver will only convert a certain amount into activated vitamin D3 (1,25-dihydroxyvitamin D3).  The D3:activated D3 ratio is influenced in an exponential curve, which means that once you take a large amount of D3 for your dose, there is no sense in taking much more because you will not be forcing your liver to activate equally that much more.  it will only activate just a little bit more.  it's a rate-limited metabolism I guess from the overwhelming of the P450 enzymes such as CYP27A1.

Edited by holdout, 11 July 2014 - 07:21 PM.

this? http://www.nature.co...ki2012338a.html

 

I wonder how safe 10,000iu Calcitriol / day is?

 

 

I'm not speaking for the safety of that but, my last vitamin D, 25-hydroxy test result (two weeks ago) was 49.8 ng/mL.  To achieve that level, I take 12,000 IU of D3 (as soft gels) six days a week.  And have done so for several years. 

Everyone is different.... Even an outdoors person, if living north of the latitude of Washington, DC, will simply not get enough UV sunlight in winter due to the low angle of the sun.  I change my dose between 2000 and 4000 at the solstices, which maintains a level around 42.  My wife, on the other hand, is not outdoors as much, but needs half as much to maintain the same levels.  She is slightly fairer than me, which might account for it.