by Nils Osmar. June 10, 2022. Medical disclaimer
I’ve been taking two sirtuin 6 activators, Gaia Herbs’ Black Elderberry Extract and DoNotAge’s SIRT6 Activator, for about a year.
I started taking them because of several studies showing that activating sirtuin 6 extends both the lifespan and healthspan in lab animals. Sirtuin 1 improves health span; Sirtuin 6 has been found to extend lifespan, which the sirtuin 1 gene has not.
A recent study
This 2021 paper by Dr. Vera Gorbunova and two other researchers explains the association between fucoidan and longevity. See study: Sirtuin 6: linking longevity with genome and epigenome stability From the study:
While gene knockouts often lead to various pathologies and shortened lifespan in mice, the most remarkable feature of SIRT6 is that its overexpression extends mammalian lifespan… SIRT6 overexpression improved various aspects of organismal homeostasis and promoted healthspan on multiple levels .
One of the important aspects involving SIRT6 in longevity is its remarkable ability to influence metabolic pathways. SIRT6 deficiency impairs hepatic ability to perform β-oxidation .
SIRT6 overexpression promotes β-oxidation in liver, hepatic lactate and glycerol shuttling, improves nicotinamide adenine dinucleotide (NAD+)/NADH ratio, and stimulates glycerol release from adipose tissue. In addition, overexpression of SIRT6 improves the capacity to produce glucose, which decreases with age .
Metabolic regulation is intimately connected to the development of cancer, which becomes more prevalent with age. Interestingly, SIRT6 overexpression leads to a decrease in the incidence of neoplasms in aged mice .
This effect is likely to result both from improved genome stability and from SIRT6-mediated transcriptional regulation of metabolic processes, such as repression of glycolysis and suppression of Warburg effect [24, 33]. – linking epigenetics, regulation of metabolism, cancer and aging.
The positive effects of SIRT6 on healthspan are not limited to metabolic regulation, as SIRT6 overexpression ameliorates endothelial cell dysfunction, improves adult neurogenesis, decreases infarct size and neurological deficit in a stroke model, protects from kidney injury and colitis, and helps maintain genomic stability in the brain [25, 29, 34–39]. Intriguingly, genetic polymorphisms in SIRT6 have been found to be associated with human longevity, however, the role these polymorphisms play in SIRT6 expression and function remains to be elucidated [40–43].
Moreover, a polysaccharide fucoidan, isolated from brown algae has shown robust SIRT6 activation in vitro, and has been linked to multiple health benefits in humans…
Another interesting study
Another recent study, published in Nature Communcations, was called Restoration of energy homeostasis by SIRT6 extends healthy lifespan, From the study:
SIRT6 represses glycolysis in an HIF1α-dependent manner32, thereby acting as a tumor suppressor by inhibiting the Warburg effect33. Liver-specific deletion of SIRT6 results in increased glycolysis, triglyceride synthesis, reduced β-oxidation, and fatty liver formation…
Here, we show that overexpression of SIRT6, but not SIRT1, extends lifespan in C57BL/6JOlaHsd mice in both sexes.
Overexpression of SIRT6 reduced the age-related metabolic decline in energy metabolism pathways and inhibited frailty by preserving hepatic NAD+ levels, GNG capacity, and maintenance of normoglycemia, key markers of healthy aging. These results emphasize the potential of targeting SIRT6 for maintaining energy metabolism and reducing age-related frailty…
Animal vs. human studies
The studies I cited above are intriguing, but have the common problem of being an animal study, meaninng that we have to extrapolate the results to humans, which always has an element of uncertainty. Critics have pointed out that there’s no direct proof that activating the sirtuin 6 gene will make us live years or decades longer.
This is a valid criticism, but it’s also true of every anti-aging product. The reason we test on animals is that they have relatively short lifespans; it would take longer than a typical human lifespan to “prove” beyond doubt that a supplement or other protocol extends the lifespan in human beings.
The sirtuins are promising because they’re highly evolutionarily conserved; the same anti-aging pathways exist in humans, mice and other complex organisms.
How to activate the SIRT6 gene
You can activate the sirtuin 6 gene strongly in a number of ways. One is to do a water fast for ten days or more. (Shorter fasts have other benefits but have not been shown to activate sirtuin 6.)
Another is to take a compound called fucoidan, a natural organic compound found in some types of seaweed and brown algae.
Another is to take a supplement that’s rich in cyanidin, found in berries. The berry with the largest quantity of bioavailable cyanidin is the elderberry.
When I originally became interested in SIRT6 activation, I started taking Doctor’s Best fucoidan supplement.
It’s possible that it may have been having benefits that I wasn’t aware of, but I felt nothing when taking it. I don’t mean this as a put-down of Doctor’s Best; I take some of their other products and like them; but I stopped taking their fucoidan after finishing off two two bottles, because of the lack of any noticeable effect.
I next tried Gaia Herbs’ Black Elderberry Extract. This is anecdotal of course, but I would say that I got a slight energy boost from taking it. (This may have been, though, because there are four grams of sugar in a teaspoonful of the product.)
I then added DoNotAge’s SIRT6 Activator, taking it along with the elderberry product and also adding 1 gram of NMN (also from DoNotAge). My reason for taking SIRT6 and NMN together is that the sirtuin genes are NAD+ dependent; they’re most effective if NAD levels are high in the body.
Taking them together, I felt an immediate improvement in both my physical and mental energy. It went beyond the slight energy boost that I’d felt from taking the elderberry alone. I feel a boost within a half hour of taking NMN and SIRT6 activator, both in my mental energy and alertness, and in my sexual energy.
As weeks went by
Some supplements bother me and I stop taking them; others seem to have no effect at all (at least that I can feel); others have positive effects and I keep taking them.
As I mentioned, I felt an improvement in my physical and mental energy after starting the above supplements (along with an array of other supplements I’d already been taking). (For a full list of my current supplements and when I take them, see this article.)
I had been taking DoNotAge’s SIRT 6 Activator along with Gaia’s Black Elderberry Extract for about two months when I noticed some changes in my body.
- One change was that the hair on my arms, chest and torso, which had gotten kind of white and wispy… my chest hair was looking a bit like the fly-away hair on Bernie Sanders’ head… had gone dark again, and was much more lush and thick than it was previously. Another was was that my sex drive increased during this period, and has stayed high.
I discuss some of these changes in this video:
A more recent change is that I have fewer, as in almost zero, aches and pains after hitting the gym. I had DOMS (delayed onset muscle soreness) for the first few months after I started working out; it went away shortly after I started taking SIRT6 Activator.
I don’t know whether this is cause and effect, but it’s consistent with the known anti-inflammatory effects of fucoidan. See article: Fucoidan as bio-functional molecule: Insights into the anti-inflammatory potential and associated molecular mechanisms,
I do notice when I take SIRT6 activator by itself that it’s mentally stimulating, kind of like having drunk or four cups of coffee. I’ll often take it before or shortly after taking a cold shower, as cold exposure is another way of activating the sirtuin (survival) genes.
Can sirtuin gene activators make you sick?
In terms of the specifics of sirtuin 6 activators, elderberries (fresh from the plant) contain small amounts of cyanide. Are they still in elderberry syrup? According to this Healthline article, the answer is no. The author states:
However, commercial preparations and cooked berries do not contain cyanide, so there are no reports of fatalities from eating these. Symptoms of eating uncooked berries, leaves, bark, or roots of the elderberry include nausea, vomiting, and diarrhea (2).
Fucoidan supplements are derived from seaweed and brown algae. Some people have raised concerns that taking them could increase iodine levels in the body, and could in theory result in thyroid problems.
Iodine is beneficial in proper amounts, but it’s true that too much can be problematic. I don’t know of any studies showing that fucoidan supplements contain enough iodine to cause problems. (I’ve searched but have not found any studies validating that concern.) I eat a lot of Wakame (seaweed), use a naturally iodized sea salt, and take 2 capules of SIRT 6 activators a day; I plan to have my iodine checked in a few months; if it’s high I’ll cut back on the seaweed. DoNotAge has had their product analyzed and published the results; it has just a trace amount of iodine.
Why Gaia Herbs and DoNotAge?
Gaia Herbs has been around for decades, and has an excellent reputation for quality. I’ve had good experiences taking their supplements. One interesting thing about their approach is that they track every plant the goes into every bottle of their supplements.
What interested me about DoNotAge’s approach was that they had wild-sourced the seaweed it was derived from, and that, according to several statements made by their CEO, they test every new strain of seaweed or algae in Vera Gorbunova’s laboratory to make sure that it actually is activating the sirtuin 6 gene before including it in their product. (This was actually what made me switch over to DoNotAge.) If the strain they’re testing doesn’t activate the sirtuin 1 gene, according to their public statements, they throw it out it and try again.
The world of supplements is a kind of wild west in which quality varies widely. I’d be delighted to see every company follow suit and start testing all of their products to verify that (1) their supplements contain what they list on the label; (2) that the ingredients are pure, fresh and potent; and (3) that they’re effective for their intended purpose.
The cost of supplements
Supplements cost a lot of money. For those taking, or considering taking, DoNotAge’s SIRT6 Activator or their other products, their discount code is the word PATHWAYS in all caps.. Unfortunately I don’t have a discount code for Gaia at this time.
If I were in a financial crunch, I might try taking the supplements every other day instead of every day. I currently take most weekends off from supplementing, partly to save some money; partly because I think it’s good to cycle supplements; and partly because when I start taking them again on Monday, I feel a definite boost from doing so.