Resveratrol is a natural polyphenol molecule that has been shown to have anti-aging properties. It is found in plant sources such as grapes, apples, blueberries, plums, peanuts, and other oilseeds.
Many studies suggest that resveratrol is a potent activator of the Silent Mating Type Information Regulation 2 Homologue 1 (SIRT1) longevity gene, leading to a more youthful appearance and longer lifespan.
SIRT1 is an enzymatic protein found in our body. Its level decreases as we age, making us more prone to age-related diseases. Researchers contend that if SIRT1 levels can remain active and increase, lifespan can be extended.
So, does resveratrol activate SIRT1, and does it work as advertised? Let’s look at the evidence.
Some controversy suggests that resveratrol (RSV) does not activate SIRT1. This article will scrutinize the evidence to help determine what is fact and what is misinformation. For example, a YouTube video by Dr. Brad Stanfield, at 6:00, claimed in a particular experimental study a certain dye was the direct activator of SIRT1 and not resveratrol. This is the study: (Pacholec et al., 2010)(Pacholec M, Bleasdale JE, Chrunyk B, Cunningham D, Flynn D, Garofalo RS, Griffith D, Griffor M, Loulakis P, Pabst B, Qiu X, Stockman B, Thanabal V, Varghese A, Ward J, Withka J, Ahn K. SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1. J Biol Chem. 2010;285:8340–8351. [PMC free article] [PubMed] [Google Scholar]).
This article will scrutinize the evidence to help determine what is fact and what is misinformation.
Scientific Evidence Showing That Resveratrol Does Not Activate SIRT1
The study published in 2010 claims, after conducting an elaborate and detailed experiment, that resveratrol is not a direct activator of SIRT1 and has little or no effect on SIRT1 activity. But instead, it was a particular dye called “TAMRA fluorophore” that was used in the experiment with the resveratrol, that caused the SIRT1 activity.
However, later studies conclusively discredited the above study. A 2018 research report published the following:
- “An opposing model to direct SIRT1/activator binding suggested that STACs produced complexes with the substrate fluorophore in solution, leading the authors of that study to conclude that STAC effects on cells and animals may be indirect (Pacholec et al., 2010). However, extensive mechanistic and structural studies of the past five years have conclusively established that STACs directly interact with SIRT1 and other isoforms and that the FdL fluorophore actually mimics natural amino acids that occur on native Sirtuin substrates (Cao et al., 2015; Dai et al., 2015; Dai et al., 2010; Gertz et al., 2012; Hubbard et al., 2013; Lakshminarasimhan et al., 2013b).“
The 2018 study continues with this statement:
- “However, extensive mechanistic and structural studies of the past five years have conclusively established that STACs directly interact with SIRT1 and other isoforms and that the FdL fluorophore actually mimics natural amino acids that occur on native Sirtuin substrates (Cao et al., 2015; Dai et al., 2015; Dai et al., 2010; Gertz et al., 2012; Hubbard et al., 2013; Lakshminarasimhan et al., 2013b).”
Note: You will find these excerpts in Section “Pharmacological Sirtuin modulation.” Then scroll down to subsection “Mechanisms of Sirtuin activation.” Also, note that STACs stands for Sirtuin Activating Compounds. The researchers are using this abbreviation for resveratrol and several other compounds.
The bottom line is that the 2010 study that claimed TAMRA fluorophore dye was the reason for SIRT1 activation and not resveratrol was wrong in their assessment and results. It is null and void, and no other follow-up studies have ever been conducted on the dye.
Scientific Evidence Showing That Resveratrol Does Activate SIRT1
In 2003, scientists were able to extend the life of Saccharomyces cerevisiae (a type of yeast). They experimented with numerous plant polyphenols to activate SIRT1. However, the one that stood out as the king was resveratrol. It activated SIRT1 more than 10 fold, extending the yeast’s lifespan by 70%.
A study published in February 2013 conducted an experiment to ultimately determine if, in fact, RSV could activate SIRT1. The researchers contended that “resveratrol’s direct activation of SIRT1 has been refuted several times” in the past, and there was a lot of controversy among RSV’s claims as being a SIRT1 activator.
The scientists not only proved that resveratrol is a potent activator of SIRT1, but they thoroughly showed the mechanism behind it. The researchers stated, “In our recent paper, this mystery is resolved to a great extent, and a mechanistic explanation of resveratrol’s activation of SIRT1 has been provided.”
Another 2020 study published in Frontiers Pharmacology expressed the following on resveratrol:
- “RSV was shown to be involved in the activation of macrophages, T cells, and natural killer cells, as well as in the suppression processes of CD4+ CD25+ regulatory T cells (Yang et al., 2008; Svajger and Jeras, 2012). All these effects are due to its ability to remove ROS, inhibit cyclooxygenase (COX), and trigger anti-inflammatory pathways via SIRT1 activation (Miceli et al., 2014; Malaguarnera, 2019).”
A 2018 report (in section 3.5) described how a study was done on 11 people with obesity problems showed that resveratrol mimicked calorie restriction and increased the levels of SIRT1.
A May 2021 study declared that resveratrol could activate SIRT1 the same way calorie restriction does, causing an ergogenic (exercise performance enhancer) effect and improving insulin sensitivity.
Yet another study from January 2022 (Section 2) stated that RSV’s ability to activate SIRT1, it was able to relieve inflammation caused by numerous diseases.
It is evident that resveratrol can and does activate SIRT1!
The following image shows how resveratrol interacts with SIRT1 within a cell:
Resveratrol uses three different mechanisms to sneak through a cell’s outer layer (the membrane).
- Passive diffusion – the resveratrol molecule passes through the cell wall without using any energy. It travels from a high concentration area (outside the cell) to a low concentration area (inside the cell). It’s similar to you stepping out of a crowded room.
- Carrier-mediated transport (carrier protein) – specific receptors on the membrane recognize the resveratrol molecule and transport it into the cell.
- Endocytosis via lipid rafts – lipid rafts are receptors found on the cell’s membrane. They regulate cell functions and are like traffic cops, but instead of guiding cars, they guide proteins, lipids, viruses, etc. They let the resveratrol molecule by, and then it is engulfed into a vesicle (endocytosis) to be transported into the cell.
Once the resveratrol molecule is inside the cell, via any of the aforementioned mechanisms, it activates SIRT1. (See source at section 2)
Resveratrol has been nicknamed the “Miracle Molecule” and for good reason. Countless human studies support the nickname. RSV has been beneficial to people suffering from diabetes, cancer, cardiovascular disease, obesity, inflammation, and more.
But what tops all these benefits is that RSV is one of the most powerful natural SIRT1 activators in the world. Lab, animal, and human studies have proven this. SIRT1 is a longevity gene, and as such, adding resveratrol to your supplement regimen will only help increase your lifespan and health span.
Does resveratrol activate SIRT1? After you look at the evidence, how can you claim that it doesn’t!!!!!