#1

SIRT6 is a protein deacylase, deacetylase, and mono-ADP-ribosylase (mADPr) regulating biological pathways important for longevity including DNA repair and silencing of LINE1 retrotransposons. SIRT6 knockout mice die by 30 days of age, whereas SIRT6 overexpression increases lifespan in male mice. Finding safe pharmacological activators of SIRT6 would have clinical benefits. Fucoidan, a polysaccharide purified from brown seaweed, has been identified as an activator of SIRT6 deacetylation activity. Here, we show that fucoidan also activates SIRT6 mADPr activity, which was shown to be elevated in certain human centenarians. Administering fucoidan to aged mice led to a significant increase in median lifespan in male mice. Both male and female mice demonstrated a marked reduction in frailty and epigenetic age. Fucoidan-treated mice showed repression of LINE1 elements suggesting that the beneficial effects of fucoidan are mediated, at least in part, by SIRT6. As brown seaweed rich in fucoidan is a popular food item in South Korea and Japan, countries with the highest life expectancy, we propose that fucoidan supplementation should be explored as a safe strategy for activating SIRT6 and improving human healthspan and lifespan.

Full paper here:

6 Likes
#2

Interestingly, I just read this:

2 Likes
#3

Interesting. I just started taking fucodian to improve the health of my endothelial glycocalyx (I have plaque).

Here’s a study that led me down this path:

Fucodian isn’t expensive, and I’ll do a repeat endoPAT in a couple of months to assess.

2 Likes
#4

Reading that study, they say:

“Our findings suggest that fucoidan may be an essential component responsible for protecting the eGC in acute settings.”

What reason is there to suspect that fucoidan is beneficial for endothelial glycocalyx (eGC) in people who do not have CKD? If this were true of eGC in general, outside of the action of uremic toxins specifically (originating in the diseased kidney), wouldn’t they generalize it to eGC globally, rather than focusing on uremic toxins and furthermore, in acute settings, i.e. not slow deterioration as in plaque formation?

It’s interesting, but uncertain to me (who doesn’t have CKD) if it’s applicable outside of this specific setting.

2 Likes
#5

Survival

IMG_1976
IMG_19762041×940 122 KB

2 Likes
#6

It depends on a brand. High purity from Japan $760 for 750 ml ($30/1 fl oz)
https://a.co/d/hNlNL4g

2 Likes
#7

I took endocalyx for a while and it’s not cheap even by my standards.

#8

Unfortunately, on top of the lack of effect on maximum lifespan or either parameter in females, the males appear to be short-lived (median 750-775 days based on the survival curve), so this seems likely to be noise.

3 Likes
#9

@Bicep That’s why I’m giving fucodian a go. Hoping for a benefit at a lower cost.

1 Like
#10

@CronosTempi Indeed, I found no studies looking at the effect of fucodian on arterial plaque. I’m basing my trial entirely on some admittedly weak signals that it may improve the health of the endothelial glycocalyx in non acute situations. I’ll report back in a couple months, after a repeat endoPAT.

1 Like
#11

This was my initial thought too, per the 900 day rule, but I was looking at some ITP data and ~800 day median seems normal for control males, while female controls tend to have the 900 median.

And indeed the 900 day rule paper confirms ~800 is pretty normal for het males, while females tend to make it to 900 https://www.biorxiv.org/content/biorxiv/early/2023/10/10/2023.10.08.561459/F4.large.jpg

2 Likes
#12

Which means they’re still short lived and so should be skeptical. Doesn’t look like a big effect if any.

#13

A few things here. First, while it is indeed common for male mice (these weren’t HET3 mice: they were C57Bl6 —but it’s true for both) to have a median LS of 800 days, the point of the 900 day rule is not to say what’s common, but what level of control health is needed for results to be reproducible. The further you fall below 900 days, the less likely it is.

Second, in this study, the median LS of the controls was not even 800 days, but 750-775, which is well short of the standard.

Third, most of the LS studies done in HET3 are done by ITP, and (a) ITP results have the built-in advantage that the studies are run independently in three different labs, so you can see whether it’s reproducible from the get go, and (b) when you look into the details of the ITP winners, usually the controls from at least one of the 3 sites has a much shorter median LS than the other labs, which drags down the overall median and inflates the overall effect size, whereas you’re usually getting two centers finding the drug works more modestly but with greater confidence with longer-lived controls. (In the early days, it seemed like UT Austin had a problem, whereas these days it seems less consistent). See for instance Supplemental Table S1 from this paper.

2 Likes
#14

Now I don’t feel too bad having just reordered my years supply of Sirt6 activator from Do Not Age for £400

#15

This resonated with me. I take the Matakana fucoidan brand almost every day (I live in Australia and struggle to find fucoidan) . I chatted to Prof Maruto on this as he spent about three decades researching fucoidan and he recomended it to me as I am trying to inhibit the PI3K-AKT-mTOR pathway as I have an acoustic neuroma.

2 Likes
#16

Tnx for the nudge re adding fucoidan. hansensuppliments.com, IMHO a reliable and pure suppliment supplier added fucoidan powder.$109 (euro) for 50g powder. I get my apigenin, fisetin, luteolin, from hansen too.

Take care all, curt

1 Like