Longevity research has identified three important signaling pathways in the body that slow down the aging process and promote health. They act as energy and nutrient sensors in the body and react to changes in our cells. Each actor has its own mechanism that regulates bodily functions and the ageing process.
All three pathways work together synergistically and are essential for our organism. Nevertheless, they have different effects on the processes that influence our longevity and on various metabolic pathways. – Longevity Lifestyle: AMPK. Sirtuine, mTOR.
Sirtuins – the switches of longevity
Sirtuins are special proteins in the body that play an important role in controlling our genes. To understand how they do this, we must first consider how our DNA is packaged in the cells.
Imagine our DNA as an incredibly long string – if you strung the DNA of all the cells in our body together, it would cover the distance from the earth to the sun a thousand times! Ultimately, this enormous length has to fit into our tiny cells. To make this possible, our body winds the DNA onto tiny “coils” called histones. The DNA packaged in this way is then neatly stowed away in the cells.
Now the sirtuins come into play. They have the ability to modify the histones, which influences which genes can be transcribed and which cannot. They act like switches that can turn certain genes on or off. This is why they are also referred to as “epigenetic regulators”.
NAD – without this coenzyme, sirtuins are powerless
However, in order to operate these switches and activate our longevity genes, the sirtuins require a special coenzyme called NAD (nicotinamide adenine dinucleotide). With increasing age, however, the amount of available NAD in the body decreases. Without this essential cofactor, the sirtuins can no longer work effectively and their activity decreases. It is thought that this is one of the reasons why we become more susceptible to illness as we get older.
AMPK – the energy conductor of the cell
Finally, adenosine monophosphate-activated protein kinase (AMPK) also plays an important role. AMPK is an enzyme in our cells that influences insulin sensitivity and glucose uptake in the cells. It is like a guardian that constantly checks whether our cells have enough energy. When energy becomes scarce, AMPK kicks into action and ensures that more energy is made available.
At the same time, AMPK inhibits the antagonist mTOR (“mechanistic target of rapamycin”), which controls energy production in our cells. If mTOR is too active, the cells use more energy to control anabolic processes. AMPK therefore ensures that our cells use their energy efficiently when food is scarce. However, AMPK does even more for our cells. It helps them to obtain energy from fats and promotes autophagy, a process in which the cells cleanse and rejuvenate themselves.
AMPK and health: the key role in metabolic processes
The activation of AMPK can be influenced by various factors, and there are several reasons why many people have difficulty activating AMPK effectively:
- Sedentary lifestyle and lack of physical activity:
An inactive lifestyle and lack of physical activity can lead to insufficient AMPK activation. AMPK is activated by muscle contractions during exercise, but people who do little or no exercise may have reduced AMPK activity.
- Unhealthy diet:
An unbalanced diet with an excess of calories, especially carbohydrates and fats, can impair AMPK activation. A high calorie intake, especially from poor sources, can lead to an increase in ATP (adenosine triphosphate) and hinder AMPK activation.
- Insulin resistance and obesity:
People with insulin resistance or obesity often have problems activating AMPK. Insulin resistance can disrupt the AMPK signaling pathway, leading to reduced AMPK activity. Being overweight can also impair the function of AMPK in fat cells.
Ageing process
The ageing process tends to lead to a decrease in AMPK activity. This may contribute to older people having difficulty activating AMPK effectively, which can have an impact on metabolism and energy homeostasis. Energy homeostasis describes the balance between supplied and released energy that the body needs for optimum performance.
Genetic factors
Individual genetic predisposition can also play a role in AMPK activation. Some people have genetic variations that can affect AMPK function. However, our DNA does not necessarily determine our health destiny: we ourselves can positively influence our genes with the new longevity lifestyle by switching them on or off!
Chronic stress
Chronic stress can disrupt the energy balance and inhibit AMPK activation. Stress hormones can influence the AMPK signaling pathways and thus disrupt normal activation.
Insufficient activation of AMPK can accelerate the ageing process and shorten the lifespan and, in particular, the health span. The diabetes drug metformin and the natural plant substance quercetin can activate the AMPK signaling pathway in the body and improve insulin sensitivity.
How you can activate AMPK
Activation of adenosine monophosphate-activated protein kinase (AMPK) can be achieved in various ways, such as through lifestyle changes, diet, exercise and certain medications. Our BIOCOACH offers this Longevity Lifestyle as a compact program.
Here are some strategies to activate AMPK:
1. regular physical activity
- Aerobic training: Endurance training such as running, cycling and swimming can activate AMPK as it affects ATP and AMP levels
- Resistance training: Strength training can activate AMPK, especially in the muscular system
2. calorie restriction and intermittent fasting
Reduced calorie intake and intermittent fasting can activate the AMPK signaling pathway, as they lead to an increase in AMP in relation to ATP.
3. healthy diet
- A low-fat, high-fiber diet, low in saturated fat and rich in fiber, can support AMPK activation
- Foods that promote AMPK: Green tea, curcumin (in turmeric), resveratrol (in red grapes) and omega-3 fatty acids (in fish) can activate AMPK
4. metabolic stressors
Cold or heat therapy and sauna visits can generate metabolic stress and activate AMPK.
5. food supplements
Certain dietary supplements can support AMPK, e.g. berberine, alpha-lipoic acid and quercetin.
According to German and European law, NMN (nicotinamide mononucleotide) is a chemical that is suitable for human consumption.
6. medication
Some medications, such as metformin (a diabetes medication) and AICAR (an AMPK activator), can support AMPK activation.
However, it is important to mention in this context that any lifestyle changes, such as the intake of dietary supplements or medication, should always be made in consultation with a doctor. The individual response to these interventions can vary from person to person and is always dependent on various factors such as state of health, genetic predisposition and current medication.
Is mTOR evil? Longevity requires a fine balance
mTOR, or “mechanistic Target of Rapamycin”, is a key player in our body when it comes to cell division and growth. When our body has plenty of energy, mTOR is activated and uses this excess energy to promote the development of muscles and tissue. An example of the effect of mTOR can be found in people who regularly do strength training and consume a lot of animal protein. Through their diet and exercise habits, they increase the activity of mTOR in their bodies, which leads to an increase in muscle mass.
This is particularly important in old age, as maintaining and building muscle mass can protect against sarcopenia, the age-related loss of muscle mass, and general frailty. But as with many things in life, there is a downside. Excessive activity of mTOR can suppress the activity of our longevity genes. From an evolutionary point of view, this makes sense: if there is enough food and therefore energy available, the body concentrates on growth and reproduction rather than on prolonging life: in evolutionary terms, it is mainly about survival and reproduction and less about the individual living as long as possible. It is therefore important to find a balance in mTOR activity to support our health and fitness as well as our longevity.
Plant-based proteins and intermittent fasting: finding the balance with mTOR and taking advantage of its benefits
We all need mTOR to form new cells and maintain our muscle mass. But: excessive mTOR activity has a negative effect on our longevity. An effective way to regulate mTOR activity is to practice moderate calorie restriction or intermittent fasting.
Both strategies can help to temporarily inhibit mTOR and thus maintain the balance in the body. It is also important to pay attention to our diet. Animal protein from meat, fish and dairy products can stimulate mTOR and thus promote cell growth and ageing. A healthier alternative is plant-based proteins, which are found in foods such as lentils, beans and pseudocereals like quinoa. They stimulate mTOR less strongly and should therefore be the preferred main source of protein in our diet.
Summary – Longevity Lifestyle: AMPK, Sirtuins, mTOR
AMPK, sirtuins and mTOR are the three most important longevity players. On a cellular level, their interaction determines whether our body is geared towards longevity or not. Sirtuins are important longevity switches in our cells. They work together with NAD and help to activate our longevity genes.
AMPK and mTOR are two enzymes in the body that work as antagonists. Studies have shown that increased AMPK activity leads to an increased lifespan and healthspan, promotes autophagy and improves insulin sensitivity. Its counterpart mTOR, on the other hand, is active when there is an energy surplus and uses this to initiate anabolic processes such as muscle building. Although mTOR is essential for the body, a permanently increased mTOR activity is associated with an inhibition of the longevity genes.
To promote a balance of AMPK and mTOR, moderate calorie restriction, intermittent fasting or the consumption of plant protein instead of animal protein is suitable. Micronutrients such as quercetin also help to activate the AMPK pathway, inhibit mTOR and boost longevity processes.