Altered (macro-) autophagy or, more vividly altered cellular waste disposal is the twelfth and last Hallmark of Aging. What science means by this is that our cells are no longer able to get rid of cell waste. This can affect large molecular complexes or entire cell organelles – hence the prefix “macro” – but also the smallest deposits, such as those seen in Alzheimer dementia finds. For the sake of simplicity, in the rest of the article we will only talk about autophagy .
Why does cellular waste disposal play such a big role? To answer this in more detail, we will take you on a little journey through the body and introduce you to the various components of your waste disposal system . Don’t be intimidated by complicated names like Autophagic-lysosomal system or Chaperones , we explain everything to you here 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 weakening recycling system.
What is autophagy?
Autophagy describes the cell's own recycling. It is completely normal for proteins or other cell components to eventually lose their function or are no longer needed. After all, our needs change over time. Our cell power plants – the mitochondria – also 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 incorrect breakdown of proteins, for example – the loss of proteostasis – we have already identified as a Hallmark of Aging can identify. Incorrectly folded proteins can no longer be unfolded. This poses 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 standalone Hallmark since the last update. We'll show you here what exactly happens with age.
From scissors to acid traps – how is the waste in our cells disposed of?
Before we look at what goes wrong as we get older, we should first take a closer look at our recycling system. It is elegantly designed and does its work day after day without us noticing.
Roughly speaking, there are two major systems in the waste disposal of the cells. The first has the awkward 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 imagine the proteasomes as a kind of filter with highly specialized scissors inside. Every protein that gets into the proteasomes is carefully separated and is then available to the cell again as a new building block.
The second large system has the no less complicated name Autophagic-lysosomal system. This has a more complex structure than the UPS, as it not only breaks down individual proteins, but in case of doubt entire cell organelles are broken down into their building blocks and these are then returned to the cell metabolism.
The 4th Hallmark of Aging is largely due to a malfunction of the ubiquitin-proteasome system. This is about autophagy.
Just as mountains of rubbish often accumulate in nature, this also happens to us as we age.
The autophagic-lysosomal system
In our cells, not only faulty proteins are a problem, but also cell organelles that no longer function. We have already written detailed articles about the role of ATP and the mitochondria , but they reveal little about what happens when old mitochondria have to be broken down. This happens through macroautophagy.
Again simplified here: A shell forms around the old mitochondrion, which in its entirety is called autophagosome . Now we have a protected environment. This is necessary so that the breakdown inside the cell does not destroy the entire cell.
In the next step the autophagosome connects to the lysosome. This is a type of small stomach - it contains a lot of digestive enzymes that we need to break down complex molecules. Everything is now broken down within this protected environment 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 fed into the cell and the waste materials are transported away with the lymph fluid.
Lipofuscin – when you can literally see your age
As we age our highly specialized recycling system can no longer keep up. If we stay with the lysosomes, this can be seen impressively. 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 with the lymph or bloodstream. This “hazardous waste” is stored in the cell in small capsules, so-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 essentially “clogs” the cell and thus limits its function. This is probably one of the reasons why mitochondrial dysfunction occurs in old age.
Age spots can be seen not only in nerve cells under the microscope, but also in aging skin.
Alzheimer's disease - one of the most prominent examples of incorrect waste disposal
Another disease that is associated with improper waste disposal is Alzheimer's dementia. This is where so-called amyloid plaques are deposited. Due to incorrect breakdown, these complexes accumulate in the nerve cells and “garbage” them.
In addition, the Tau protein is altered in Alzheimer's patients - 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 previously incurable disease.
Sleep – a long-underestimated remedy
There are many ways to help our body with autophagy. A very promising one is sufficient sleep. While we sleep peacefully, our brain is tidying up. The so-called glymphatic system ensures that the waste products of the day are removed.
For a long time, sleep was neglected in medicine, but We now know that sleep is extremely important for our health. If we don't sleep enough for months or years, the cellular waste cannot be removed properly and the risk of Alzheimer's increases.
Mitochondria and autophagy – when strength is lacking in old age
We have already seen with age spots, the Lipofuscin, what happens to old mitochondria that can no longer be broken down properly. Defective mitochondria and the lack of them are associated with typical signs of aging such as heart failure, but are also one of the drivers for the 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 it is central to the provision of energy. Just like the mitochondria, the NAD content decreases with age. This can be done e.g.b through NAD tests, which measure the NAD concentration in the blood.
Studies have now shown that administration of NAD precursors, as contained in NAD boosters, not only correct the NAD levels, but also increase autophagy. In animal experiments, this even extended life.
regeNAD is an innovatively formulated complex to increase NAD levels - with luteolin and apigenin.
Fasting – an autophagy boost
Abstaining from food in the form of fasting can also 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.
If 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. The chaperones are therefore activated within a very short time. Chaperones are specialized proteins that primarily take care of the correct folding of proteins. But they also play a role in autophagy by transporting proteins that they can no longer fold correctly to the lysosomes and thus ensuring their degradation. True cavaliers then.
Fasting ensures that our body restarts its own recycling system in various ways. Be it through the activation of the Sirtuine, via which Dr. David Sinclair did research, or through the chaperone system. Take a similar approach Fasting Mimetics as you can find in the Fasting Bundle find.
Spermidine – a promising molecule
Another very exciting approach to boost autophagy in old age is 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 underway in humans. In mice, spermidine supplementation has already been able to extend life by up to 25% . A spermidine-rich diet in humans has also been linked to better health.
According to research, the natural substance spermidine is closely related 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 appears to be overwhelmed by the amount of waste 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 again as one of the hallmarks of aging, be it through fasting, Exercise, Buy spermidine or NAD precursors.
We will be excited to see what new approaches will come onto the market in the next few years and whether we can use them to prevent diseases such as Alzheimer's at some point.
This was the last article in the series Hallmarks of Aging.
