Causes of Aging: Loss of Proteostasis

by | Aging, Longevity

purple proteins on blue background

Each cell in our body contains millions of proteins. Proteins are the building blocks of our cells. Proteins are also the working horses given they carry out most of the functions in our cells.

For example, there are proteins that form channels (gates) in the membranes of our cells to let substances in and out of cells.

Muscle proteins inside muscle cells can contract, so the muscle cells become shorter and our muscles can contract.

Proteins in the membrane of brain cells transmit electrochemical signals or pump out neurotransmitters.

Proteins in our gastric cells produce gastric acid. Long protracted proteins form beams that give cells their shape, or anchor them to other cells.

Collagen and elastin proteins outside cells provide elasticity of skin and ligaments.

Other proteins accelerate chemical reactions (these proteins are called “enzymes”), like breaking down the sugar and the fat you eat.

In other words, proteins are the building blocks of life.

 

Protein maintenance

 

Our DNA mainly contains the instructions to build proteins. A gene is a piece of DNA containing the code to build a specific protein. Our DNA contains thousands of genes to build about 20,000 different proteins.

Our cells contain millions of proteins. Most of these proteins are continuously produced and recycled.

So proteins are continuously created and broken down. Our cells contain intricate machinery (also mostly built of proteins) to break down and recycle proteins. This maintenance of proper protein metabolism happens via different mechanisms, such as (R):

Autophagy

Proteins and other waste materials are engulfed in vesicles and then transported to the lysosomes which break their contents down. The lysosomes are little sacs in the ells that contain enzymes (proteins) that break down proteins and other substances. One can consider the lysosomes as the incinerators of the cells.

There exists micro-autophagy (used to clean up small cell parts), macro-autophagy (often used to clean up larger cell parts) and chaperone mediated autophagy (to clean up very specific parts of our cells).

The ubiquitin-proteasome system

This cellular machinery looks like a tiny cylindrically-shaped “grinder” that breaks down proteins. In fact, small proteins called ubiquitin stick to specific proteins, tagging them for destruction. These ubiquitinated proteins are then transported to the proteasome, which breaks them down (the proteasome actually looks like a meat grinder).

 

Proteins and aging

 

The recycling processes we just discussed are very intricate, but they are not perfect.

During aging, our cells become less and less able to properly recycle their proteins. Proteins start to accumulate inside and outside our cells. This hampers the function of the cells. They are becoming “old”.

In other words, during aging, the proper maintenance of all the proteins inside and outside our cells (this proper maintenance is also called “protein homeostasis” or proteostasis”) becomes dysfunctional.

Proteins are not broken down and recycled properly, and start to accumulate everywhere inside and outside our cells. Also, various other waste materials in our cells start to accumulate during aging because the “biological incinerators” of the cell start to become dysfunctional.

We see that protein accumulation plays a role in many aging-related diseases. For example, in Alzheimer’s disease specific proteins (and likely others) such as tau protein, beta-amyloid protein and TDP-73, start to accumulate. This hinders the proper functioning of brain cells, eventually even causing them to die off.

In aging blood vessels, specific proteins start to accumulate, making these blood vessels more frail and prone to breaking.

In an aging heart, proteins accumulate in heart cells, impeding their function. Proteins accumulate in the blood vessel walls, making them more stiff and prone to breaking. Protein accumulation in lung tissue also contributes to more stiff and “old” lungs.

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