#185

The abstract

“Autophagy is an intracellular catabolic process that responds with great sensitivity to nutrient availability, implying that certain macro- or micro-nutrients are involved. We found that retinoic acid promotes autophagosome maturation through a pathway independent from the classic nuclear retinoid receptors. Retinoic acid redistributes the cation-independent mannose-6-phosphate receptor from the trans-Golgi region to maturing autophagosomal structures inducing their acidification. Manipulation of the autophagic activity by retinoids could have enormous health implications, since they are essential dietary components and frequently used pharmaceuticals.”

What are examples of health implications?

1 Like
#186

From the paper:

"Retinoic acid redistributes the cation-independent mannose-6-phop-shate receptor from the trans-Golgi region to maturing autophagosomal structures inducing their acidification. "

Personally I would be nervous about anything that makes cells more acidic. The cellular response to this could be to deacetylate the histone in order to get back to an alkaline state.

1 Like
#187

It has nothing to do with acidification of the cell per se… mature autophagosome is acidic. It is one of cell structures that initiates autophagy of cell. It needs to be acidic to start this process. @Melih autophagy is disrupted in cancer and number of diseases (neurodegenerative diseases, metabolic disorders, infectious diseases, premature aging…). So if we take control autophagy we might find cures for these diseases.

3 Likes
#188

Sinclair: Tretinoin is accelerating skin aging, bc it triggers cell turnover.
Also Sinclair: Microneedling is a hormetic stressor and rejuvenates skin.

3 Likes
#189

Retinoids reduce wrinkles by boosting cell growth and collagen. New study shows they might actually be slowing aging (Sirt1 ➡️ mTOR). #skincare #beauty https://t.co/NgwwIGKIpc pic.twitter.com/oOStTKM3ne

— David Sinclair (@davidasinclair) May 31, 2021

All-trans retinoic acid reduces mammalian target of rapamycin via a Sirtuin1-dependent mechanism in neurons

Neuroinflammation has emerged as a key contributor in the pathogenesis of Alzheimer’s disease (AD). Mammalian target of rapamycin (mTOR) is a key regulator of metabolism, cell growth and protein synthesis. And an elevated mTOR activity has been detected in AD-affected brain areas. Previous studies have suggested that all-trans retinoic acid (at RA) and rapamycin (RAPA), an mTOR inhibitor, protect lipopolysaccharide (LPS)-induced neuronal inflammation through inhibiting nuclear import of NFκB. The aim of this study was to test the effects of at RA on mTOR expression. Here we discovered that mTOR and p-mTOR expression are elevated in LPS-treated mice or primary rat neurons, while at RA blocks the mTOR gene upregulation via a SIRT1-dependent mechanism. The results of this study demonstrated that at RA may protect LPS-induced neuronal inflammation through suppressing mTOR signaling.

4 Likes
#190

A post was split to a new topic: Haut.AI Software Company Targeting Skin Care

#191

Another interesting paper:

The 2018 paper:

https://www.nature.com/articles/s41419-018-0765-9

7 Likes
#192

If the mitochondria are less efficient the cell has less energy and does not produce enough of the longer proteins.

1 Like
#193

Have not yet checked it carefully but … The Science | One Truth 818

#194

I’ve tried this product and at least for me it made no difference whatsoever. I gave it a month. It wasn’t well formulated, sticky and not very pleasant. There is another company called IDEO that claims to have a similar product. Currently testing that and again not really seeing an substantial improvement.

1 Like
#195

There is also The Derma company with their TA65. Expensive, ouch

1 Like
#196

I’m pretty sure that all of these products are licensed out of Bill Andrews lab. I’m not really sure what to make of him. He’s a quite well known and seemingly respected scientist in aging circles, but for all of his certainty of his research and notoriety he appears to be unable to attract any serious investment- at leas that’s what he frequently says. He seems to be licensing out his discoveries to very small companies with very little reach and I’m not sure if it’s a lack of business acumen or just a sign that what he has to offer just isn’t very compelling. The prices are insane and I can’t imagine why anyone would pay for it without some seriously amazing results, and there just doesn’t seem to be any evidence of that.

2 Likes
#197

I spoke with Matt K. at the last conference and asked about these type of telomere extending products such as from Sierra Sciences. Matt said many of these compounds have been around for many years but the fact that there is very little positive science being published on them and very few of them are duplicated by independent labs seems to suggest that there isn’t much there. If there was something there, the science should be there (at least that is is what Matt’s argument was, and I can see the case he’s making).

Personally I’m a fan of Carl Sagan. He had a saying… Extraordinary claims require extraordinary evidence"… and I tend to agree with that.

12 Likes
#198

I totally agree on this. Although some of the telomere gene therapy is quite interesting, but I’m not really convinced by any of these products that purport to extend telomere length. If there was anything in it, we’d know already.
I think Carl Sagan hit the telomere on the head there.

3 Likes
#199

Yes, if something truly works, it soon becomes a big thing because the results are seen. I am going to try Korean rejuran heal this Spring or Summer. Different mechanisms of action, not affecting telomeres but there are quite a few papers on Salmon PDRN as for a very new product and it becomes a hype in Asia. I will report to you here what my experiences are.

3 Likes
#200

Thank you. Please keep us posted.

2 Likes
#201

Are you going to do the Rejuran injections? I was confused for a while, since Rejuran makes a variety of products, both topical and injectable.

Here are a couple of good links I found

https://www.drrachelho.com/blog/rejuran-healer-pdrn-singapore/

Dr Rachel Ho | Salmon DNA in Skincare and Needleless Rejuran Healer Explained.

1 Like
#202

Skin booster. So yes, injections. Instead of HA based ones like Profhilo or teoxane which make my skin really rehydrated and nice but do not do too much for the fine lines on my décolleté. So lets’s see how salmon DNA will fare. By the way, there is also new, more concentrated HA skin booster from Korea, seventy hyal. Have not tried it yet. May do.

4 Likes
#203

FYI, there is a company offering topical rapamycin for the skin:

4 Likes
#204

Sometimes I wish I were in US….(until I watch news, that is)

6 Likes