Fucoidans (SIRT6 activators) from brown algae. Where to source?

I just received a pound of powdered bladderwrack to cook with. It seems like it would be tasty in small amounts in many savory foods, though it might be challenging to achieve the doses used in many studies. I’ll try incorporating it into bread first.

The research paper, “Anti-skin glycation and collagen level stimulation of brown seaweed extracts and their compositional characteristics,” has been published in Algal Research.

Anti-skin glycation and collagen level stimulation of brown seaweed extracts and their compositional characteristics

https://doi.org/10.1016/j.algal.2023.103257

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Waiting for the product from Israel.

Longevity focused biotech SIRTLab emerges from stealth, aiming for first human trials of SIRT6-boosting therapeutic in 2024.

“Professor Zhang explains the Flinders team has found that extracts from SA’s brown seaweed not only stimulated the growth of collagen, but also inhibited a process called glycation, which leads to the deterioration of collagen and elastin.”

I like the idea of stimulating the growth of collagen. I have taken a boatload of various direct micronized collagen supplements in the past. Mainly it just ruined the taste of my coffee. There were no subjective effects from taking collagen that I could detect.
So, I just received a new Australian brown seaweed supplement. I will give it a try and see if it has any detectable effects after using it for 3 months.

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You think this will be inexpensive?

When you see the cost you will have other thought.

Review patents.

Believe it or not, buying the same product in Hong Kong is 3X more expensive than DoNotAge.

I’m surprised that no one has posted this:

Starting at 0:55, she says that she and other groups are working to find or develop SIRT6 activators. SIRT6 has two separate enzymatic activities: deacetylation and ribosylation, and to date, all the SIRT6 activators that have been reported have been deacetylation activators. While both activities are important for cellular functions, she thinks ribosylation may be particularly important for longevity because her research found human centenarians carry rare SIRT6 variants with enhanced ribosylation activity:

Characterization of this SIRT6 allele (centSIRT6) demonstrated it to be a stronger suppressor of LINE1 retrotransposons, confer enhanced stimulation of DNA double-strand break repair, and more robustly kill cancer cells compared with wild-type SIRT6. Surprisingly, centSIRT6 displayed weaker deacetylase activity, but stronger [mono-ADP ribosyl transferase (mADPr) ] activity, over a range of NAD+ concentrations and substrates. Additionally, centSIRT6 displayed a stronger interaction with Lamin A/C (LMNA), which was correlated with enhanced ribosylation of LMNA.

Her group went back and tested the reported activators to see if they also activated its robosylation activities, and found that fucoidan does. However, there are a diversity of different fucoidan molecular structures, with different backbones and degrees of sulfation, and not all fucoidan molecules work the same way: some even inhibit SIRT6. This was mentioned in the opening post by Alex:

Another naturally occurring molecule showing SIRT6 activation is fucoidan (4), a heterogeneous sulfated polysaccharide present in brown algae. Its backbone consists of repeating (1 → 3) or (1 → 3) and (1 → 4) linked α-l-fucopyranose residues, in which some hydroxyl groups form sulfated esters (Figure ​Figure55, lower panel).123 The oversulfated fucoidan subtype extracted from Fucus vesiculosus displayed a 355-fold increase of SIRT6 activity at a 100 μg/mL concentration. In addition, when tested against other SIRTs (SIRT1/2/3), it did not display significant changes in activity, suggesting a specific action toward SIRT6. 4 was also able to activate SIRT6 acetylation toward H3K9 in vitro. According to the authors of the study, sulfate esters may play a central role in SIRT6–4 interaction and hence SIRT6 activation.123 However, the heterogeneity of the mixture, the polymeric nature of the compound, and the absence of kinetic data makes it difficult to compare this macromolecule to small molecules and to devise structure–activity relationships.
Crude fucoidan content in two North Atlantic kelp species, Saccharina latissima and Laminaria digitata—seasonal variation and impact of environmental factors - PMC

Gorbunova is working with sugar chemists to identify the key chemical structures responsible for the SIRT6 activating activity. This would allow them to make a better (and presumably patentable) drug.

Starting at 5:38, Gorbunova has done experiments with their specific “crude extract” of fucoidan extract (“not just ground up seaweed”) as a SIRT6 activator. From what she says later on, it appears this is the extract used by DoNotAge. (No, I have no affiliation or conflict of interest). The mice were given the fucoidan extract in their chow, and “there was clear benefit:” it lowered frailty scores and inflammatory cytokines, improved physical activity, and increased lifespan. She estimates the human-equivalent dose would be 4 g of extract (which would be TEN of DoNotAge’s capsules).

She has tested DNA’s extract and confirmed that it activates SIRT6.

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If you search for “Gorbunova”, it will show that her work has been discussed; maybe not this particular video, but her work on Sirt6 and fucoidans.

Thanks. Clearly many people in this thread aren’t aware of those discussions, since people are talking about using plain bladderwrack powder, random fucoidan extracts, and questioning whether DNA does any testing of their SIRT6 activator.

This video is more detailed about Gorbunova’s testing every batch of the DNA product:

She says that only 3 out of 10 batches of brown seaweed activate SIRT6.

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. There are quite a few other substances that are said to activate sirt6. Black elderberry looks promising.

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Yes, but (as I cited Gorbunova saying in my first post) all of these activate its deacetylase activity, but only (some) fucoidan extracts activate the ribosylation activity which seems to be the activity relevant to human longevity.

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fucoidan extended lifespan of mice only by 6.8% while transgenic SIRT6 overexpression mice led to 27% extension, I wonder why.

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Thats easy… in a transgenic mouse they are modifying the level of SIRT6 over expression in every cell in the mouse’s body, so its basically the best and most potent case.

In a situation where a mouse is consuming something - much of it gets broken down in the gut, and little of it penetrates a significant portion of the cells of the body.

They are two very different situations. A consumed compound will never, I suspect, get close to the efficacy of a transgenic model organism.

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The transgenics also have elevated SIRT6 activity in their cells 24 hours a day from the time they’re conceived until the day they die. Gorbunova only started her mice on fucoidan at age 14 months (middle age), and the ‘drug’ is presumably only active for a few hours after they eat. So the fucoidan mice lost the equivalent of decades of slower aging.

It’s a cumulative thing — like the difference between people with loss-of-function PCSK9 mutations versus people who start on a PCSK9 inhibitor in their 50s or 60s after decades of accumulating atherosclerotic disease.

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I wonder if buying and consuming brown algae directly might be an easier approach. With this mind…

  1. Has anyone been able to figure out which 3 of 10 algae tested actually increased fucoidan? I’m assuming bladderwrack is one of them as that’s what they put into DoNotAge supplement. But there is also Mozuku, Kombu, Wakame, etc.

  2. Has anyone been able to find a good place to buy them in the US? I see that bladderwrack is available on Amazon, but I haven’t tried it yet.

Another relevant video:

The study evaluated senolytic effects and compared Fucoidan to Rapamycin.

DoNotAge has a good Sirt6 Activator product. It’s good but pricey.

I am thinking of just reaching out to Vera G. and the authors of this study for suggestions on what species of seaweed may be best:

FWIW, Mozuku is commonly consumed in Okinawa. There is also this study on traditional foods of Ogimi, Okinawa. The authors list multiple types of seaweed:

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I just bought some random fucoidan off amazon. Had no idea there was such a large family to choose from. Mine came from Patagonian Undaria Pinnatifida algae extract. Interested to see what you find out.

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I’ve just tried Wakame (Undaria Pinnatifida), Wel-Pac brand (available in HMart and on Amazon) and found it a surprisingly good addition to my meals. I can see myself eating it regularly, so can recommend that others give it a try too. I just mix it with kale, EVOO, mustard seeds, balsamic vinegar, capers, and olives in sort of a fusion cuisine type of salad.

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