The mitochondrial dysfunction is a central point in aging research. Often referred to as the “powerhouses of the cells”, the strength and efficiency of our mitochondria diminishes with ageTo make matters worse, old mitochondria can no longer be broken down properly and clog the cells until they lose their function. Many of the metabolic pathways associated with age take place in the mitochondria or are involved in them. An example would be the NAD.
Here we show you what happens in our mitochondria, how age affects our cell organelles and what we can do to possibly reverse this hallmark of aging.
The mitochondria – a small miracle of nature
Mitochondria are found in varying numbers in the body's cells and are one of many structures that contribute to proper cell function. Muscle cells, sensory cells or egg cells are cells with a high energy requirementAccordingly, there are an above-average number of mitochondria in these cells. In a heart muscle cell, the volume share even reaches an extraordinary 36%. This is already an indication of the great importance of these cell organelles.
The body’s own power plants have a special feature: They have their own DNA, the so-called mtDNA (from English mitochondrial DNA), which floats around in a ring-like manner inside the mitochondrion. However, this does not allow for independent reproduction. Only 37 genes includes the mitochondrial genome in humansFor comparison: the DNA in the cell nucleus contains the information for 20,000-25,000 genes.
Did you know? In contrast to our DNA in the cell nuclei, mtDNA lies unprotected in the cytoplasm of the mitochondria. This makes them particularly vulnerable to oxidative stress. Our body’s own protective glutathione and antioxidants, which we find mainly in secondary plant substances find.
respiratory chain, energy supply and NAD+
As is well known, energy is produced and provided in the mitochondrion. This process is called cellular respiration and takes place via the respiratory chain – an interaction of 5 protein complexes that form an electron transport chain. electrons (negatively charged particles) play an important role in the energy production process. At the beginning of the respiratory chain is the molecule NADH, which can release two electrons in the process of generating energy. This ultimately creates ATP and the "waste product" NAD+. NAD+ is nothing other than the molecule NADH, only one proton (positively charged particle) and two electrons poorer.
Long story short: The energy production in our cells consists of splitting off the electrons contained in food. During this process, energy is released. High NAD+ levels This means that a lot of NADH is converted to ATP, meaning that the cell can produce a lot of energy. This is a good sign.NAD+ subsequently activates sirtuins, a group of genes associated with longevity. More on that later.
Did you know? NAD levels decrease with age. This can be easily measured with a NAD test The reasons for this are varied, from reduced production to increased mining. We have provided you with a detailed presentation of the current research in our overview article “What is NAD“ summarized for you.
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Free radicals – reactive oxygen species (ROS)
A selected theory of aging proposes that the progressive mitochondrial dysfunction that occurs with aging leads to increased production of free radicals (= reactive oxygen species, ROS) reactive oxygen species). This further damages the mitochondria and thus leads to general cell damage. antioxidants are of interest.
Numerous studies support this connection, but in recent years there has been increasingly controversial research results. For example, increased free radicals could extend the lifespan of yeast and nematodes. In addition, genetic manipulations that caused oxidative damage did not accelerate aging in mice. Nor did manipulations that improved antioxidant protection mechanisms extend the lifespan of mice.
At the same time, basic research provided solid evidence for the Role of free radicals in triggering of cell division and survival signals in response to stressIn view of these and many other surprising results, the theory began to falter - a reassessment became necessary. Similar to the IGF-1 signaling pathway Here too, it was possible to harmonize the, at first glance, contradictory results under a common roof.
Accordingly are ROS is a stress-related survival signal to compensate for the deterioration associated with agingThe number of free radicals increases to ensure the survival of cells. At least until they betray their original purpose and worsen rather than alleviate the age-related damage due to the massive increase. It could also be summed up differently:
We need ROS, they can act like training partners for our cells. But if there are too many of them, they cause damage to our cells.
Mitochondrial Dysfunction and Biogenesis
However, aging due to mitochondrial dysfunction is not only mediated by free radicals (ROS). We will take a closer look at a number of other factors. As with so many processes in the body, the gene family of sirtuins also important here. SIRT1 modulates biogenesis via a protein called PGC-1α.This protein is the master regulator of mitochondrial biogenesis and a direct link between external physiological stimuli (such as exercise) and mitochondrial regulation.
A more tangible Example: If young children participate in sports that require endurance, then fast muscle fibers (for sprints) are reprogrammed into slow muscle fibers (for endurance). These muscle fibers have a lot of mitochondria to ensure sustained energy supply.
The amount of mitochondria is determined by PGC-1α – a high level ensures increased mitochondrial production. However, a certain basic distribution of muscle fibers is genetically determinedThe smaller variable part, however, is controlled by physical demands via PGC-1α. Parents can therefore indirectly influence the muscular development of their children by choosing the type of sport.
Did you know? While exercise can increase PGC-1α levels, care for inflammations that PGC-1α decreasesTypically, NF-kB is activated during inflammatory processes in the body and this can have a direct negative effect on PGC-1α. This shows once again that the various Hallmarks of Aging interact with each other and are difficult to separate. Inflammaging, the tenth Hallmark, therefore directly contributes to mitochondrial dysfunction.
Back to the longevity pathways. SIRT1 also controls the removal of damaged mitochondria by Autophagy, a kind of garbage disposal in the bodySIRT3 targets enzymes involved in energy metabolism and can also directly control the rate of free radical production.
From a bird’s eye view, these results support the assumption that Sirtuins act as a kind of metabolic sensors to influence the function of mitochondria and protect against age-related diseasesSince mitochondria have their own small genome, corresponding mutations in the genetic information naturally also disrupt their functionality.
From Theory to Practice
So much for the molecular mechanisms in the mitochondrial structure. What do these findings mean for our everyday lives? Studies have shown that endurance training and alternating Fast improve health, as they can prevent mitochondrial degeneration. This is due to the fact that Autophagy, which can be potently triggered by both fasting and endurance training. On the other hand, various forms of fasting provide additional Longevity pathways, such as sirtuins, activated.
Mitohormesis – small stimuli, big effect?
This somewhat mysterious-sounding term consists of mitochondrion and hormesis together. According to the concept of hormesis mild toxic treatments trigger beneficial compensatory reactions.The compensatory reactions exceed the repair of the initiating damage and thus lead to an improvement in cellular fitness compared to the state before the damage.
This hypothesis goes back to Paracelsus and thus to the 16th century. Over time, this view was experimentally supported and used in substances such as digitalis (heart failure), colchicine (gout) or opiates (Pain) has also been made medically usable.
A number of lines of research on aging have also focused on this concept. Although severe mitochondrial dysfunction causes disease, only mild disturbances could prolong lifespan due to a hormetic responseThere is scientific evidence to support the view that metformin and resveratrol are mild mitochondrial poisons that induce a low energy state and thereby increase AMP levels. We already know the consequence from the discussion on deregulated nutrient measurement: AMPK is activated and thereby slows down aging.
Metformin prolonged the life of roundworms and mice in some studies. Under normal nutritional conditions, resveratrol does not extend the lifespan of mice, but there are significant study results that show that protects against metabolic damage and improves mitochondrial function by increasing PGC-1α. The observation that PGC-1α overexpression extends the lifespan of fruit flies provides further evidence for the protein's role in longevity.
Summary of signaling pathways surrounding mitochondria and aging. Mitohormesis, PGC1a and free radicals are believed to have a protective function.
Conclusion – how can mitochondria be strengthened?
Mitochondria are not only the powerhouses of the cell, but also potential sources for healthy agingFunction, or rather non-function, has a profound influence on the aging process.
The studies show quite clearly that by sport eg strengthen mitochondria Endurance and strength training, even into old age, form the basis. In addition, we must protect the mitochondria from excessive oxidative stress by eating a diet rich in secondary plant substances. Resveratrol, for example, has been shown to have a positive effect on mitochondria.
Mitochondrial health is always closely linked to NAD levels. Since these decrease with age, it may make sense to supplement the precursors, as they are found, for example, in regeNAD are included. The last aspect of strengthening our mitochondria is to ensure that the “disposal” of old mitochondria works smoothly. altered (macro-) autophagy However, it represents a very unique hallmark of aging, which is why we will examine this aspect in more detail in another article.
In conclusion, mitochondria are a fascinating aspect of aging research.The goal for the future is to find out more about why mitochondria become less efficient as we age and how we can reverse this. The first steps have already been taken.
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The next article in this series is about the seventh hallmark of aging: Cellular senescence.
