Natural Sirtuin Activators

As someone who values their health and wellbeing you are no doubt familiar with NAD+ and likely how they exert their beneficial effects via sirtuins. If not don’t worry you are in the right place to get all that information. However, if you want to know the best compounds to take or include in your diet to increase sirtuin activation and reap the numerous benefits associated with that then continue reading to get the latest scientific information.

Sirtuins activate Longevity Pathways

Sirtuins are the family of proteins that elicit the body’s response to calorie restriction and exercise. In addition to mediating repair pathways that protect cells from oxidative and DNA damage. There are seven sirtuins (SIRT1-7), the most studied being SIRT1. They have become a focus of research as they help prevent age-related diseases such as cancer, cardiovascular disease, osteoporosis, and diabetes. Sirtuin activity is innately linked to NAD+ levels within the cell, only being activated when NAD+ is bound to them. Therefore, as NAD+ levels decline with age so does sirtuin activity.

The health benefits of sirtuins include antioxidant, anti-inflammatory, cardioprotective, neuroprotective and anti-tumor. As a result, identifying compounds both natural and synthetic which activate sirtuins is of great interest. This article will detail the most common natural compounds that can boost your sirtuin activity.

There are several natural compounds found in food that are extremely effective at activating sirtuins in our cells. The most well studied and characterized include:

• Pterostilbene

• Resveratrol

• Metformin

Resveratrol has Low Bioavailability

Within the literature you may see reference to STACs, these are simply sirtuin activating compounds. The first generation of STACs were discovered by drug screening panels. Although the specific methods of the screen were later called into question the results were not. The initial screens identified the compound resveratrol which increased SIRT1 activation by more than 10-fold. Resveratrol is a stilbene polyphenol, a natural compound found in grapes, blueberries and peanuts.

Unfortunately, further studies highlighted that it had very low bioavailability, with most of the active compound being excreted during metabolism. However, there are other natural compounds in the polyphenol family which also have potent activity. These include chalcones (e.g. butein) and flavones (e.g. quercetin). All these compounds share a backbone structure of phenol rings with hydroxyl groups attached.

 Pterostilbene: the upgraded resveratrol

Pterostilbene is resveratrol’s cousin, another member of the polyphenol stilbene family. The difference in structure is minimal but this change makes all the difference. Pterostilbene has a better bioavailability (the amount of the compound that is available to the cell after metabolism) as it is better at entering the cells. It can do this because it has better lipophilicity. This simply means it can dissolve better than resveratrol in fats, oils, and lipids. The improved bioavailability and ability to cross the blood brain barrier has earned pterostilbene the title of the upgraded resveratrol.

Pterostilbene has gained notoriety for its ability to improve memory, cognition and learning. It increases levels of dopamine and repairs neurons in the memory centers of your brain (the hippocampus). It activates the same pathways as calorie restriction to change gene expression and provide neuroprotection. 

Metformin

Metformin is a biguanide drug used to treat type 2 diabetes. It lowers blood glucose, promotes glucose uptake in peripheral tissues and promotes the breakdown of fatty acids to reduce weight. Metformin has been used clinically for ~60 years yet only now are we appreciating the variety of beneficially effects it has on health and aging. It has been shown to delay aging in animal model as it targets the insulin/IGF-1 pathway in addition to the AMPK/mTOR pathway. It is the latter which involved SIRT1. Metformin indirectly activates SIRT via AMPK activation. However, it could also act as a direct SIRT1 activator, but further research is required to determine the details.

Currently, there is growing interest in the anti-aging potential of metformin with the TAME (targeting aging with metformin) clinical trial being established. This trial aims to establish aging as a disease and demonstrate it can be treated as such.

These are just a few of the most common SIRT activators. They either activate SIRT directly or activate the upstream pathway to exert the plethora of health benefits. No matter how you chose to tackle sirtuin activation whether supplements, diet, exercise the benefits are undeniable.

Learn more about Sirtuin activation and NAD.

Learn more about the mitochondria: the key component to aging.

References;

• Amidfar, M., de Oliveira, J., Kucharska, E., Budni, J., & Kim, Y. K. (2020). CREB and BDNF: Neurobiology and treatment of Alzheimer's disease. Life sciences, 118020.

• Bonkowski, Michael S, and David A Sinclair. (2016) Slowing ageing by design: the rise of NAD+ and sirtuin-activating compounds. Nature reviews. Molecular cell biology. 17,11: 679-690.

• Salehi, B., Mishra, A.P., Nigam, M., Sener, B., Kilic, M., Sharifi-Rad, M., Fokou, P.V.T., Martins, N. and Sharifi-Rad, J., (2018). Resveratrol: A double-edged sword in health benefits. Biomedicines, 6(3): 91.