It’s been known for a while that SIRT6 activation is associated with a significant increase in lifespan in lab animals, and that SIRT6 activation is NAD+ dependent. (It works best when NAD is available in the body when the sirtuin 6 gene is activated.) The SIRT6 gene has been found to extend the lifespan in lab animals and to have other benefits.
Compounds which are known to activate SIRT6 include fucoidan (from some types of seaweed) and cyanidin (from black elderberry), and an herb called Yin Yang Huo, or horny goat weed. Yin yang Huo is rich in a compound called icariin which also activates the sirtuin 6 gene.
In a recent study entitled Icariin Intervenes in Cardiac Inflammaging through Upregulation of SIRT6 Enzyme Activity and Inhibition of the NF-Kappa B Pathway, the authors stated::
We conclude that icariin (ICA) had a stimulatory effect on SIRT6 enzyme activity in vitro, even at very low concentrations. ICA can upregulate SIRT6 protein expression and downregulate NF-κB (p65) protein expression in murine heart tissues and in an aortic EC model.
ICA upregulated the expression of SIRT6 and had an inhibitory effect on NF-κB inflammatory signaling pathways by decreasing the mRNA levels of NF-κB downstream target genes TNF-α, ICAM-1, IL-2, and IL-6. Those effects were mediated directly or indirectly by SIRT6.
We have provided tentative evidence that inflammaging may involve a link between the effects of ICA on SIRT6 (a regulator of aging) and NF-κB (a regulator of inflammation).
Icariin Extends Lifespan in Mice
According to this study, Icariin has been found to extend the lifespan in lab animals. From the study:
We have previously reported that icariin extended the healthspan of invertebrate models. Here, we showed that long-term treatment with icariin starting at 12months of age extended healthspan and mean lifespan in C57BL/6 mice.
In all our assays associated with healthspan, such as behavioral tests and bone density analysis, we found that icariin boosted healthy features in mice… Our results indicated that icariin, a safe and widely used natural flavonol, extended healthspan and maintained genomic stability in a mammalian system.
Does NMN activate SIRT6
According to a March 2022 study, NMN is also a potent SIRT6 activator – or can be under some circumstances.
… The in vitro and in vivo results described in this study show that NMN exerts an antioxidant effect on early tendinopathy by increasing the expression of sirtuins… NMN increased the expression of SIRT1 and SIRT6 in rat tenocytes… In Achilles tendons with collagenase-induced tendinopathy, NMN increased the mRNA expression of SIRT1 and SIRT6.
From a 2017 study:
Brown seaweeds contain many bioactive compounds, including polyphenols, polysaccharides, fucosterol, and fucoxantin. These compounds have several biological activities, including anti-inflammatory, hepatoprotective, anti-tumor, anti-hypertensive, and anti-diabetic activity, although in most cases their mechanisms of action are not understood.
In this study, extracts generated from five brown algae (Fucus dichitus, Fucus vesiculosus (Linnaeus), Cytoseira tamariscofolia, Cytoseira nodacaulis, Alaria esculenta) were tested for their ability to activate SIRT6 resulting in H3K9 deacetylation.
Three of the five macroalgal extracts caused a significant increase of H3K9 deacetylation, and the effect was most pronounced for F. dichitus. The compound responsible for this in vitro activity was identified by mass spectrometry as fucoidan.
Implications for Humans?
Do these studies, taken together, prove that if we take supplements such as NMN, which increase NAD levels in the human body and also activate SIRT1 and SIRT6, we’ll live longer? Not necessarily. For one thing, we’re not lab animals. (As scientists are fond of saying, people are not just big mice.) And most people who take NMN are doing so orally, not by injection.(In the NMN study it was given by injection, not in the animals’ food or water.)
What I’m Doing
I’m more impressed by sirtuin 6 than sirtuin 1 in terms of possible life-extending benefits. I try to take SIRT6 activators along with NAD boosters every day.
My morning cocktail includes 1.5 grams of NMN; 0.5 grams of NR, 1200 mg of SIRT6 Activator (all from DoNotAge), along with a teaspoon of black elderberry extract from Gaia Herbs. (I often take them along with a “Fasting Mimicking Smoothie” which is high in oleic acid from avocado, which has also been shown to be a sirtuin activator.)
This part’s purely anecdotal, but I can report that I feel a physical and mental boost when taking them. I sometimes also take a capsule of horny goat weed at the same time. I notice a greater boost from taking them together than taking each of them separately. This could a placebo effect, but I suspect that due to the multiple sources of SIRT6 activation, and the fact that NMN itself is not only raising NAD+ levels but activating the SIRT6 gene. I’m hoping to live longer in better health as a result.
If I had to choose one
I like the “cocktail supplement” approach; it makes sense to me to reinforce longevity pathways using multiple supplements. But if I had to choose just one sirtuin 6 activator, I would take DoNotAge’s SIRT6 Activator, due to its having been vetted by Dr. Vera Gorbunova’s lab.
- Antioxidant effect of nicotinamide mononucleotide in tendinopathy
- Restoration of energy homeostasis by SIRT6 extends healthy lifespan
- The Identification of a SIRT6 Activator from Brown Algae Fucus distichus