How loss of proteostasis affects aging

Proteostasis is a compound word meaning “protein stasis” — the normal balance of proteins in our cells. When proteins work together, our cells carry out their functions properly. However when we lose proteostasis, our cells stop getting the right instructions and they can mutate, stop working, or even die. That leads to signs of aging such as uneven skin tone, rough texture, and fine lines and wrinkles.

One reason we can lose proteostasis is oxidative stress, when free radicals overwhelm our systems. Free radicals come from pollution, smoking, UV light, and fried foods. Try to avoid these causes, and help fight free radicals using antioxidants. Qyral skincare products all contain antioxidants designed to fight free radicals. You can also get antioxidants from your diet, in fruits, vegetables, nuts, and green tea.

What are proteins and what do they do?

Diagram of amino acids

The proteins in our body are large, complex molecules made of chains of amino acids. We have 20 different types of amino acids that combine to make different proteins. For example, some make proteins that support our immune system as antibodies. Others form enzymes, which translate the code carried in our DNA. Still more provide support, energy, and storage for our cells. Proteins regulate almost every function our cells perform and that makes them super important to our overall health.

The instructions for making proteins are found in RNA (ribonucleic acid). RNA is a key part of the “central dogma of molecular biology” — the rule for how cells process information. DNA contains the genetic code for the entire organism. RNA translates that code and creates proteins. Animal cells have around 20,000 genes dedicated  to coding proteins. Plant cells have even more, about 30,000. Proteins are fundamental to every step of our cells’ formation and behavior.

What is proteostasis?

Proteostasis is short for “protein stasis.” Stasis means “to stay the same,” so the term refers to the state of our proteins being stable and error-free. Proteostasis is the normal, desirable state of things where everything works properly.

To maintain proteostasis, our cells make new proteins and fix or recycle broken ones in a process called autophagy. Think of a mechanic tinkering with a car engine to keep it running. Scientists call the system responsible for maintaining our proteins the “proteostasis network.” It’s made out of many proteins itself. These include:

• Ribosomes — that turn RNA instructions into new proteins.
• Chaperones — to help new proteins form into the correct shape.
• Lysosomes — digestive enzymes that break down damaged or unnecessary proteins.
• Ubiquitin — molecules that tag proteins if they need to be repaired or recycled.

All the proteins and molecules in the proteostasis network come together to keep other proteins in check.

What factors affect proteostasis?

We need the proteostasis network because our bodies are extremely complex. With all the millions of chemical reactions and actions they perform daily, it's no surprise that mistakes happen. Proteins can misfold, and this can be catastrophic to the cell. Misfolded proteins are associated with neurodegenerative diseases like Alzheimer's and Parkinson’s, as well as age-related conditions such as type 2 diabetes, cataracts, and atherosclerosis. Sometimes proteins can even become infectious, at which stage they are known as prions. They cause brain diseases such as Creutzfeldt-Jakob Disease (CJD).

Misfolding isn't the only risk factor for proteostasis. Some cancers turbocharge protein production, especially proteins that moderate cell growth and metabolism. In fact, some cancer drugs deliberately disrupt proteostasis to stop cancers from growing.

Obesity also puts strain on the proteostasis network, which prevents it from adapting to other stressors. The result is metabolic diseases such as type 2 diabetes.

Simply getting older also puts increased strain on the proteostasis network in the form of oxidative stress. This is a buildup of molecules containing unpaired electrons, known as free radicals. Free radicals “steal” electrons from elsewhere in the body, destabilizing surrounding cells.

We create free radicals as a byproduct of other chemical processes. In small numbers they could even be beneficial as a kind of early warning system. However we also absorb free radicals through our environment — from pollution, tobacco smoke, UV light, and fried food. When free radicals get out of hand, which is more likely as we get older, the result is oxidative stress. This is a cascade of damage done to our cells when too many become destabilized at once.

One of the places free radicals steal electrons from is proteins. When this happens, the protein can become misfolded, or it can lead to aggregation. This is the term for clumps of proteins sticking together. When aggregation happens, all the proteins in the clump stop working and can damage or even kill surrounding cells. Protein aggregates are considered toxic because of the harm they can do. Proteotoxicity is associated with age-related conditions such as heart disease.

Once an aggregate has formed, it can trap other proteins, leading to a whole series of blockages. Additionally, prions can attach to aggregates to avoid detection.

Many factors affect proteostasis and result in imbalances in the system. Temperature and pH fluctuations, pollution, and oxidation can all cause proteins to misfold. Mutations in DNA can mix up the instructions for making proteins. And RNA can translate information wrong. This can lead to misformed proteins, aggregates, and the loss of the proteostasis.

Sometimes chaperones get tangled in aggregates and cannot function. This is a hallmark of degenerative diseases like Alzheimer's and Parkinson's. And the more damage occurs, the greater the impact on proteins, cells, and our overall health.

How can we protect and support our proteins

So how can we protect proteins and support proteostasis? Some damage is inevitable because of the scale of our cellular functions. Of the billions of chemical reactions happening every moment, some are bound to go wrong. The good news is, our bodies compensate for these errors. We have checks and balances in place that capture most of them so they never trouble us.

Leading a healthy lifestyle is a great way of supporting our bodies. Exercising regularly, avoiding fried food and tobacco, and eating a balanced diet, are all important steps we can take.

Reducing calorie intake could also help support proteostasis. When we don't have fuel to burn, our bodies burn proteins instead. This triggers a clear out of old, damaged proteins, preventing them from forming aggregates.

We should also try to combat oxidative stress. Free radicals damage proteins, so avoiding them can help support proteostasis. The best way to do this is to get more antioxidants from your diet, skincare products, and supplements. Good sources of antioxidants include fresh fruit and vegetables, lean proteins, and nuts.

Researchers are exploring other supplements for supporting proteostasis. One candidate is Rapamycin, an immunosuppressant drug. It works by increasing protein cell turnover (autophagy). That's an important function of the proteostasis network, so boosting it could be a big breakthrough. However rapamycin also has several negative side effects that make it unlikely to be used for longevity in its current form.

In the future, it may be possible to recreate the molecules that regulate proteins. Some supplements already provide the building blocks of those molecules. In theory, these could support proteostasis by providing the tools your body needs. Examples include:

• Glycine, an amino acid that makes chaperone molecules
• Amyloid inhibitors that prevent proteins from clumping together
• Lithium, pterostilbene and glucosamine, which can induce autophagy
• Hyaluronic acid, which can trigger a defence mechanism to break up aggregates

In conclusion

Proteins are necessary for almost all our cellular functions. Proteostasis is the name for the state when our proteins are working as they should. Loss of proteostasis is a risk factor for many degenerative and age-related diseases. We can protect and support proteostasis by leading healthy lifestyles. Supplementing our diets with the building blocks of important molecules may also help. Maintaining proteostasis is an important factor in longevity, and loss of proteostasis can have a detrimental effect on our bodies at a cellular level.