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3 Pathways of Aging: AMPK, sirtuins, mTOR, which is the best to maximize longevity and lifespan?

longevity Pathways of Aging AMPK, sirtuins, mTOR

Over the past decades, many studies and researches have been done to discover the best way to maximize longevity. Therefore, there are several different approaches that prove the improvement and extension of longevity and lifespan. Various methods have shown success in different model organisms. Scientists went a step further and believe they have found several ways to activate anti-aging processes within the body. AMPK, sirtuin, and mTOR are the main pathways we are going to explain. In this article, we will get across these pathways, why they are important, and which one is the best to live better and longer.

The 3 key pathways that regulate the process of aging

Aging has been considered an inevitable, unstoppable, and natural cycle. ‘Natural causes’ are the leading cause of death in the elderly, even when they die from a variety of pathological conditions. But not everyone thinks so. David Sinclair, a biologist at Harvard, argues that aging should not be seen as a natural consequence of the life cycle but as a condition. Aging, he says, is a pathology and as such can be treated. In his book ‘Lifespan’, he claims that the key is in epigenetics. He talks about the main 3 pathways including AMPK, sirtuin, and mTOR.

AMPK (AMP-activated protein kinase) helps the cells to restore energy. It is activated whiting the body during exercise or calorie restriction. Sirtuins are proteins that are capable of delaying the aging process. mTOR is a key for cell growth, stimulated by growth factors and nutrients. Let’s dig a little deeper.


AMPK stands for 5′ adenosine monophosphate-activated protein kinase. It is an enzyme that regulates energy metabolism, increases fat burning, lowers blood sugar, and blocks fat and cholesterol synthesis. AMPK is one of the ways to increase longevity because actually can increase the number of new and healthy mitochondria.

Through its activation, it will support autophagy and put chronic inflammations aside. AMPK is activated by increasing levels of AMP (adenosine monophosphate) and decreasing levels of ATP (adenosine triphosphate). When AMPK is activated, cells do not make or store fat, but rather they burn fat for energy. Activated AMPK promotes efficient, rapid release of energy, resulting in low blood sugar and fat levels, increased insulin sensitivity, and a low risk of heart disease and other metabolic disorders. AMPK activation promotes autophagy as well. Autophagy is a process that eliminates damaged DNA, which is another cause of aging.

High levels of inflammation inhibit AMPK activation. Foods rich in omega3s like fish, fruits, vegetables rich in polyphenols, green tea, hesperidin reduce inflammation and help in AMPK activation. Also, omega3s fatty acids can increase the adiponectin hormone which activates AMPK. Another way to activate AMPK is by pharmaceutical medication. While most people are skeptical about taking drugs, there are some benefits from them. Metformin might be one of the medications that can activate AMPK.


The sirtuin genes, also known as “longevity genes”, are proteins that affect the quality of health and life. In humans, the most important are Sirtuin-1 and Sirtuin-3, because it has been determined that we can influence on them through diet and exercise. Sirtuin-1 affects fat cells by accelerating fat metabolism, preventing their storage, and inserting them into further energy consumption according to the body’s needs. It also affects muscle fibers and mimics the effects of muscle exercise. Sirtuin-3 is located in the mitochondria, where stimulates and maintains mitochondrial functions.

Sirtuins can’t work properly without a molecule called NAD+. As we age, the NAD+ levels are decreasing. Thus taking NAD+ precursors, such as NNM and NR, will boost NAD+ levels which will automatically activate the sirtuins. NAD+ is like fuel for sirtuins to work. Another and more optimal way in which we can influence sirtuin genes is through diet. All plant foods are important in the human diet because of their content of vitamins, minerals, and antioxidants.

However, we cannot stimulate these genes with any fruit or vegetable, but only with specific plant foods that have a high content of different types of polyphenols – compounds that are the main activators of the sirtuin genes. Some of them are onion, parsley, kale, green tea, cocoa, olives, dates, tofu, and many more. This way of stimulating the sirtuins is far more effective because it has the same effect on these genes and is not stressful for the body, such as calorie restriction (starvation) and exercise.

Another ingredient that can significantly activate the sirtuins genes is resveratrol. Resveratrol is a phytochemical that has been shown to activate sirtuin genes with consequent beneficial effects on aging and ease metabolic diseases.


The mammalian target of rapamycin (mTOR), plays an important role in human growth. It regulates proliferation, growth, and survival,  by stimulating growth factors and nutrients.

The best way to activate mTOR is by exercise because it can repair damaged cells and promote muscle growth. mTOR is also activated by IGF-1 (insulin-like growth factor 1), which is primarily found in animal products and amino acids. Too much mTOR activation may lead to certain diseases like cancer, Alzheimer’s, cardiovascular diseases, and other age-related conditions. Inhibition of mTOR follows increased longevity. Rapamycin in mTOR is a compound that inhibits mTOR. One study shows that 3 months of treatment with rapamycin in middle-aged mice has increased healthspan by 60%.

The keto diet and fasting, inhibit mTOR, on the other hand, heavy lifting and protein intake can activate mTOR. Dietary compounds can also inhibit mTOR, such as curcumin, soy, broccoli, kale, cabbage, caffeine, and resveratrol found in grape and red wine.

Which is the best pathway for anti-aging?

The best way for healthy slow down the aging process is by activation of the sirtuins genes. Exercise naturally increases NAD+ levels, which activates the sirtuins. It is the best and most natural approach because you can maximize longevity without taking supplementation, like rapamycin, because it can cause several adverse effects. Sirtuin genes play a key role in anti-aging. No matter which pathway you will choose, simple lifestyle changes, such as exercising and a balanced diet are key to healthy aging and prolonged lifespan.

About us

As a professional manufacturer, Hygieia Biotechnology offers from a full formula development, dosage analysis, to formula evaluation and testing, resulting in a pure raw ingredient. All products are with a high purity level of 99%. This means that has higher absorption and bioavailability for the cells, longevity, and anti-aging. As raw materials, they have passed the toxicity test and were found to be non-toxic compounds that meet all the requirements of national standards.

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