Humanity has striven for longevity since Lucas Cranach the Elder's "Fountain of Youth" in 1546, but since its very existence. Over time, quacks became scientists and hidden mysticism became visible and verifiable facts. With the technological evolution, research was given the tools it needed to approach the complexity of the changes in the human body over time. Science has been able to identify some of the dials at the cellular level in experiments, sometimes consciously, sometimes just by chance.
Communication or the exchange of information between cells takes place mainly via small molecules and proteins. As with cell phone signals, there are one or more transmittercells and one or more Recipientcells. If the receiving cell registers the signal, chemical messengers pass the "information" along special "paths" within the cell, thereby leading to a change in the cell's activity. This change in activity can mean, for example, an acceleration or slowing down of work, but it can also lead to the cell suddenly producing completely different products.
Four Paths to Longevity
Regarding the aging and longevity, four “paths” have emerged on the molecular playground:
- mTOR
- AMPK
- sirtuins
- NF-kB
By discovering these four pathways, scientists have managed to fundamentally change our understanding of aging. The representation of these signaling pathways as pathways suggests that they are independent routes through the fountain of youth. However, this is a mistake due to the wording. mTOR, AMPK, sirtuins and NF-kB are connected to each other in many ways and sometimes depend on each other. Nevertheless, for the sake of easier understanding, we want to explore the paths towards longevity one by one. Let's get started.
mTOR – Rapamycin, mice and fasting
mTOR (mechanistic target of rapamycin) is a protein found in all mammals, including humans, that functions as a signaling hub in the cell. This means that mTOR detects and integrates many signals to control reactions such as cell growth and division, cell death, and inflammation. If mTOR is not regulated properly, this can have a negative impact on longevity and health.
Both too much activity and too little of it have been shown to be detrimental. An overactive mTOR pathway has been found in cardiovascular disease, cancer, obesity and diabetes. Too little mTOR function weakens our immune system. This can also be used medically with drugs such as rapamycin, which inhibit mTOR. If someone receives a liver transplant, for example, the immune system must be weakened so that it does not reject the new "foreign" liver.
In addition, rapamycin is the only drug to date that has consistently led to an extension of life in studies on mice. However, these mice were kept in a germ-free environment and therefore did not need a strong immune system.Nevertheless, the results are encouraging, as inhibiting mTOR activity reduced the incidence of age-related diseases such as diabetes, cancer and heart disease. Research has already taken up this interesting approach and possible anti-aging therapies based on mTOR have moved from the distant horizon into the near future.
We can also contribute to the balance of the signaling pathways independently of possible medications. The golden mean of mTOR function can be achieved by:
- a healthy lifestyle with sufficient exercise,
- occasional fasting episodes
- and the reduction of animal proteins supported in our meals.
AMPK – Metformin, free radicals and mTOR inhibition
What applies to coexistence also applies to the cell on a smaller scale. energy metabolism in balance, an improved stress resistance and one qualified housekeeping are all hallmarks of improved health span and extended lifespan. The AMPK signaling pathway (adenosine monophosphate-activated protein kinase) is involved in the regulation of all these properties and can also inhibit the mTOR signaling pathway we discussed earlier. As we know, this can have positive effects for us.
For example, AMPK ensures that the glucose from our food is converted into energy in the body and does not end up as fat on our hips or bellies. Researchers are using this mechanism to treat diabetes. metformin is approved as a diabetes medication and acts as an AMPK activator in the body. Due to the broad effectiveness of AMPK, the drug is said to have an impact far beyond diabetes. Its potential is currently being investigated in several studies.
We know from various research efforts that the reactivity of AMPK decreases with age - unfortunately. This loss impairs metabolic regulation and increases the number of free radicals in the body. These age-related changes then cause metabolic disorders and mild inflammation in the body's cells. The result: we are more likely to develop diabetes or cardiovascular disease.
Fortunately, each of us can contribute to longevity through AMPK to better preserve AMPK's functionality: Intermittent fasting, regular physical exercise and a possible weight loss.
Did you know?
Not only the diabetes drug Metformin activates the AMPK pathway, but also the naturally occurring berberine. Berberine increases natural insulin sensitivity and ensures a steady blood sugar level. This makes berberine an interesting molecule in longevity research, as it can, among other things, protect against impending insulin resistance can be useful.
Sirtuins – genes of longevity and NAD+
Sirtuins is a collective term for a family of seven proteins (SIRT 1 – SIRT 7). We can imagine this protein family as being like politicians.They determine when a project is implemented, what it should look like, whether several projects are running at the same time or whether projects are canceled. These decisions are always made, at least in theory, by politicians for the good of society or, in the case of sirtuins, for the good of the cell and the entire organism.
Due to their important role in the aging process, they are sometimes referred to as genes of longevity They are involved in cell metabolism and can regulate many cell functions, including DNA repair, inflammatory response, cell cycle or cell death.
However, just as a politician needs voters to put him in the position of making decisions, need sirtuins NAD+ to functionThis molecule is found in every cell of the human body and is an important metabolic regulator. Without NAD+ we would die - that's how important NAD+ is.
A healthy lifestyle with physical activity, sufficient Sleep and fasting episodes can support the integrity of sirtuin function. In addition, molecules have been discovered that increase NAD+ levels and thus provide fuel for the function of the sirtuins.
NF-kB – Inflammaging
Nuclear Factor kappa-B (NF-kB) is involved in the regulation of inflammatory processes. Similar to mTOR, the dose makes the poison. Inflammation is basically a good thing because it helps to fight off pathogens and protect us from harmful stimuli. Too low NF-kB functionality has negative consequences because our protective shield is weakened. Overactivation, as is often found in old age, leads to chronic inflammation, the so-called InflammagingThis hip term stands for inflammatory aging and is one of the Hallmarks of Aging.
When we think of a classic, local inflammation (mouth ulcers or joint inflammation), we usually associate it with pain and a reduction in our well-being. Inflammaging does not show these noticeable signs. Instead, a subliminal inflammation develops in many cells throughout the body, which permanently damages cell function in general. The therapeutic goal is therefore to slow down the age-related overactivity of NF-kB. A healthy lifestyle with little stress and sufficient rest proved to be beneficial.
Quo vadis?
While the chronological age is practically unchangeable, except for forgery, the same applies to the biological age different. On the one hand, age is a constantly increasing number, on the biological side it is mostly a decrease in the body's ability to adapt. This decrease can now be counteracted - if one follows the right path to longevity.
