Altered (macro-) autophagy or something more descriptive altered cellular waste disposal is the twelfth and final Hallmark of Aging. Among them Science understands that our cells can no longer get rid of the cellular wasteThis can affect large molecular complexes or entire cell organelles – hence the prefix “macro” – but also the smallest deposits, such as those found in Alzheimer's dementia For the sake of simplicity, in the rest of the article we will only refer to the autophagy speak.
Why does cellular waste disposal play such an important role? To answer this question in more detail, we will take you on a little journey through the body and introduce you to the different components of your waste disposal systemDon’t be put off by complicated names like Autophagic-lysosomal system or chaperone Don't be intimidated, we'll explain everything to you step by step. We'll also take a look at the research and explain why Sleep and the supplementation of spermidine can be a booster for a weak recycling system.
What is autophagy?
Autophagy describes the cell's own recyclingIt is quite normal that proteins or other cell components eventually lose their function or are no longer needed. After all, our requirements change over time. Our cell power plants – the mitochondria – do not last a whole human life. The task of autophagy is to ensure that these remnants are broken down correctly and the components are then reused.
The faulty degradation of, for example, proteins – the loss of proteostasis – we have already Hallmark of Aging can be identified. Incorrectly folded proteins can no longer be unfolded. This carries the risk of clumping. However, since the disposal of proteins is only a small part of cellular waste disposal, the hallmarks of aging have been expanded. Altered autophagy has been a separate hallmark since the last update. We'll show you exactly what happens to it as we age here.
From scissors to acid traps – how is the waste in our cells disposed of?
Before we look at what goes wrong as we age, we should first take a closer look at our recycling system. It is elegantly designed and does its job day after day without us noticing.
Roughly speaking, there are two major systems in the waste disposal of the cellsThe first has the cumbersome name Ubiquitin-proteasome system (UPS) and has two main tasks. On the one hand, the marking (ubiquitination) of misfolded proteins and on the other hand, the proteasomes ensure that these misfolded proteins are broken down into their individual amino acids.
You can see the Proteasomes can be thought of as a kind of filter with highly specialized scissors inside. All proteins that enter the proteasomes are carefully separated and are then available to the cell as new building blocks.
The second major system bears the no less complicated name Autophagic-lysosomal system. This is more complex than the UPS, as it not only splits individual proteins, but in case of doubt entire cell organelles are broken down into their building blocks and these are then returned to the cellular metabolism.
The 4th Hallmark of Aging is largely due to a malfunction of the ubiquitin-proteasome system. This is now about autophagy.
Just as mountains of garbage often accumulate in nature, the same thing happens to us humans as we age.
The Autophagic-Lysosomal System
In our cells, it is not only faulty proteins that are a problem, but also cell organelles that no longer function. The role of ATP and the mitochondria We have already written detailed articles, but they reveal little about what happens when old mitochondria have to be broken down. This happens through the macroautophagy.
Here again, simplified: A shell forms around the old mitochondrion, which can be seen in its entirety autophagosome Now we have a protected environment. This is necessary so that the degradation inside the cell does not destroy the entire cell.
In the next step The autophagosome connects with the lysosome. This is a Kind of small stomach – it contains lots of digestive enzymes, that we need to break down complex molecules. Within this protected environment, everything is now broken down and, as always in biology, there is now a new name. The autolysosome is the connection between the autophagosome and the lysosome.
After digestion, everything that can be reused is returned to the cell and the waste products are transported away with the lymph fluid.
Lipofuscin – when you can literally see your age
In old age our highly specialized recycling system can no longer keep up. If we stay with the lysosomes, this is impressive to see. In addition to their role as "garbage shredder“, these cell organs can also absorb large proteins that no longer have a function in the cell, but are too large to be transported away via the lymph or bloodstream. This “hazardous waste“ is stored in the cell in small capsules called “granules”.
If you look at old nerve or muscle cells under the microscope, you can also see many of these dark spots. A large part of this is lipofuscin. It consists mainly of damaged mitochondria that can no longer be broken down properly. The cellular waste basically "clogs" the cell and thus limits its function. This is probably one of the reasons why mitochondrial dysfunction comes with age.
Age spots can be seen under the microscope not only on nerve cells, but also on aging skin.
Alzheimer's – one of the most prominent examples of faulty waste disposal
Another disease that is associated with One disease associated with improper waste disposal is Alzheimer's dementia. This is where the deposition of so-called amyloid plaques. Due to faulty degradation, these complexes accumulate in the nerve cells and “clutter” them.
In addition, in Alzheimer patients, tau protein changed – a protein that is important for cell stability. The result is an unstable cell and the death of neurons.
Alzheimer's has become a widespread disease over the decades. The risk factors are partly genetic and partly lifestyle-related. Incorrect waste disposal definitely plays an important role in the development of this currently incurable disease.
Sleep – a long underestimated remedy
There are many ways to help our body to help autophagyA very promising one is sufficient SleepWhile we sleep peacefully, our brain is being cleaned up. The so-called glymphatic system ensures that the day's waste products are removed.
For a long time, sleep was treated somewhat stepmotherly in medicine, but We now know that sleep is extremely important for our healthIf we do not sleep enough for months or years, the cellular waste cannot be properly removed and the risk of Alzheimer's increases.
Mitochondria and autophagy – when strength is lacking in old age
We have already discussed age spots, lipofuscin, we have seen what happens to old mitochondria that can no longer be broken down properly. Faulty mitochondria and the lack of them are associated with typical signs of aging such as heart failure, but also one of the Drivers of age-related loss of muscles.
One of the most important molecules in the mitochondrion is NAD. This is involved in countless metabolic processes – but above all central to energy supply. Just like the mitochondria, the NAD levels decrease with ageThis can be done by NAD tests, which measure the NAD concentration in the blood.
Studies have now shown that the administration of NAD precursors, as in NAD boosters are included, not only correct the NAD levels, but also increase autophagyIn animal experiments, this even extended life.
regeNAD is an innovatively formulated complex to increase NAD levels - with luteolin and apigenin.
Fasting – an autophagy boost
The abstinence from food in the form of Fast, can be helpful for our body. We have already written about the different forms of fasting and the molecular effects in a separate article, so here is just the short version.
When we are in a state of fasting, this seems to be a kind of starting signal for our body to recycle old material. After all, there is currently no food coming in. The chaperones are therefore activated within a very short time. Chaperones are specialized proteins that mainly take care of the correct folding of proteins. However, they also play a role in autophagy by removing proteins that they can no longer fold correctly. to the lysosomes and thus ensure degradation. True gentlemen, then.
Fasting ensures that our body restarts its own recycling system in various ways. Be it by activating the sirtuins, about the Dr. David Sinclair researched, or through the chaperone system. A similar approach has been fasting mimeticsas you see in fasting bundle find.
Spermidine – a promising molecule
Another very exciting approach to To stimulate autophagy in old age, supplementation with the body’s own molecule spermidine. This molecule has already been successfully tested in several animal studies and increased cellular recycling. Spermidine appears to be particularly beneficial for the health of heart cells, which is why studies are also being conducted in humans. In mice, spermidine supplementation has already shown a life extension by up to 25% bring. Also a spermidine-rich diet in humans has been linked to better health.
According to research, the natural substance spermidine is closely linked to autophagy - a process whose discovery was honored with the Nobel Prize a few years ago.
Conclusion on Autophagy
Our cellular waste disposal system is highly complex and seems to be overwhelmed by the amount of waste products as we age. This is reflected in the development of some age-related diseases. However, we are not completely powerless. There are ways to increase autophagy as one of the hallmarks of aging, be it through fasting, Sport, Buy Spermidine or NAD precursors.
We can look forward to seeing what new approaches will come onto the market in the next few years and whether we will be able to use them to prevent diseases such as Alzheimer's at some point.
This was the last article in the series Hallmarks of Aging.
