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.)
Compounds which are known to activate SIRT6 include fucoidan (from some types of seaweed) and cyanidin (from black elderberry).
According to a March 2022 study, NMN is also a potent SIRT6 activator – or can be under some circumstances.
From the study:
… 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. It 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.
- 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