Changed (macro-) autophagy or more vividly changed cellular waste removal is the twelfth and final hallmark of ageing. Science understands this to mean that our cells are no longer able to get rid of cellular waste. This can affect large molecule complexes or entire cell organelles - hence the prefix "macro" - but also the smallest deposits, such as those found in Alzheimer's disease . For the sake of simplicity, we will only refer to autophagy in the rest of the article.
Why does cellular waste removal play such an important 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 let complicated names like autophagic-lysosomal system or chaperone intimidate you, we'll explain everything step by step here. We 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 lose their function or no longer be needed at some point. After all, our requirements change over time. Even our cellular power plants - the mitochondria - do not last an entire human lifetime. The task of autophagy is to ensure that these remnants are broken down correctly and the components are then reused.
The incorrect degradation of proteins, for example - the loss of proteostasis - has already been identified as the hallmark of ageing . In this case, incorrectly folded proteins can no longer be unfolded. This harbors the risk of clumping. However, since the disposal of proteins is only a small part of cellular waste disposal, the hallmarks of ageing have been expanded. Since the last update, altered autophagy has become a Hallmark in its own right. Here we show you exactly what happens to it as we age.
From scissors to acid traps - how is the waste in our cells disposed of
Before we look at what stops working properly in old age, we should first take a closer look at our recycling system. It is quite elegantly designed and does its job day in, day out without us noticing.
Roughly speaking, there aretwo major systems in the waste disposal of the cells. The first has the cumbersome name Ubiquitin Proteasome System (UPS) and has two main tasks. Firstly, the labeling (ubiquitination) of misfolded proteins and secondly, the proteasomes ensure that these misfolded proteins are broken down again into their individual amino acids.
You can imagine the proteasomes as a kind of filter with highly specialized scissors inside. Any proteins that enter the proteasomes are neatly separated and are then available to the cell as new building blocks.
The second large system bears the no less complicated name autophagic-lysosomal system. This is more complex in structure than the UPS, as it not only breaks down individual proteins, but in some cases 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 now about autophagy.
Just as piles of garbage often accumulate in nature, this also happens to us humans in old age.
The autophagic-lysosomal system
It is not only faulty proteins that are a problem in our cells, but also cell organelles that no longer function. We have already written extensive articles about the role of ATP and the mitochondria , but these reveal little about what happens when old mitochondria have to be broken down. This happens through macroautophagy.
Simplified here again: A shell forms around the old mitochondrion, which is called in its entirety autophagosome . Now we have a protected environment. This is necessary so that the degradation inside the cell does not immediately destroy the entire cell.
In the next step the autophagosome connects to the lysosome. This is a kind of small stomach - it contains lots of digestive enzymes, which we need to break down complex molecules. Within this protected environment, everything is now broken down and, as always in biology, there is now also a new name. The autolysosome is the combination of the autphagosome and the lysosome.
After digestion, everything that can be reused is returned to the cell and the waste products are removed with the lymphatic fluid.
Lipofuscin - when you can literally see the age
In old age our highly specialized recycling system can no longer keep up. Sticking with the lysosomes, this is impressive to see. In addition to their task as "waste shredders", 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 via the bloodstream. This "special 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 proportion of these are lipofuscin. It consists mainly of damaged mitochondria that can no longer be broken down properly. The cellular waste virtually "clogs up" the cell and thus restricts its function. This is probably one of the reasons why mitochondrial dysfunction occurs in old age.
Age spots are not only seen in nerve cells under the microscope, but also in aging skin.
Alzheimer's disease - one of the most prominent examples of faulty waste disposal
Another disease that is associated with defective waste disposal is Alzheimer's disease. This involves the deposition of so-called amyloid plaques. These complexes accumulate in the nerve cells due to faulty degradation and "clutter" 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 as yet incurable disease.
Sleep - a long underestimated cure
There are many ways to help our body with autophagy. A very promising one is sufficient sleep. While we slumber peacefully, our brain is being tidied up. The so-called glymphatic system ensures that the waste products of the day are removed.
For a long time, sleep was somewhat neglected in medicine, but we now know that sleep is enormously 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 what happens to old mitochondria that can no longer be broken down properly in the case of age spots, the lipofuscin. Faulty mitochondria and the lack of them are associated with typical signs of ageing such as heart failure, but are also one of the drivers of age-related atrophy 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 the provision of energy. Just like the mitochondria, the NAD content decreases with age. This can be z.Bdetermined by NAD tests, which measure the NAD concentration in the blood.
Studies have now shown that the administration of NAD precursors, as contained in NAD boosters , not only restore NAD levels, but also increase autophagy. In animal experiments, this even prolonged life.
regeNAD is an innovatively formulated complex to increase NAD levels - with luteolin and apigenin.
Fasting - an autophagy boost
Omitting food in the form of fastingcan 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 in. Chaperones are specialized proteins that mainly take care of the correct folding of proteins. However, they also play a role in autophagy by transporting proteins that they can no longer fold correctly to the lysosomes and thus ensure 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 sirtuins, which Dr. David Sinclair researched, or through the chaperone system. A similar approach has fasting mimetics, as you can find them in the fasting bundle .
Spermidine - a promising molecule
Another very exciting approach to boosting autophagy in old age is supplementation with the endogenous molecule spermidine. This molecule has already been successfully tested in several animal studies, where it 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 prolonged life by up to 25% . A diet rich in spermidine in humans has also been associated with 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 appears 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 again as one of the hallmarks of aging, be it through fasting, exercise, buying 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 can use them to prevent diseases such as Alzheimer's at some point.
This was the last article in the series Hallmarks of Aging.
