Aging and Disease: 2.8 Cell Senescence, Changes In Molecular Turnover, Extracellular Molecules

• Aging
• Alzheimer's
• beta amyloid
• Curing Alzheimer's
• Epigenetics
• Telomeres

The human body contains perhaps a bit short of 40 trillion cells, which is an impressive number, yet a large part of our body – a quarter to a third, depending how you measure it – isn’t intracellular, but extracellular. This includes not only the fluids within the blood and lymphatic spaces, but the space that lies between our cells, even in “solid” tissue. This extracellular space is just as critical – and as it turns out, just as dynamic – as our intracellular space.

The extracellular space has cells within it, for example the fibroblasts in our dermis, the lymphocytes wandering about in our lymphatic system, and the red and white (and other) cells circulating in our blood streams, but if we ignore all of these cells for a moment, we find that the extracellular space is still a complex place. It is replete with important molecules, including electrolytes and proteins (and many others), and these molecules are continually being “recycled”, much as the intracellular molecules are.

The extracellular space is not a quiet place and certainly not a place where protein molecules can quietly “retire” for a few decades. To the contrary, the molecules come and go, subject to continual degradation and replacement. Aging doesn’t occur simply because molecules “sit around and fall apart”. Aging occurs because molecules aren’t turned over as quickly as we age.

Looking solely at human skin – and then solely at a few of the dozens of important molecules that play a role – we find two well-known molecules that are worth focusing on: collagen and elastin. We will simplify our discussion by looking just at the skin, just at collagen and elastin, and just at both proteins generically, intentionally ignoring the multiple subtypes of both collagen and elastin. We will also simplify our discussion by ignoring the water, electrolytes, immune proteins, enzymes, hormones, and various other structural proteins (keratin, muscle, bony matrix, fibronectin, laminins, etc.) that we might discuss.

Let’s focus on what happens to the collagen and elastin in our skin as we age.

Both collagen and elastin are familiar to most of us, as well as to anyone who has ever watched advertisements for skin care products. Collagen is a long, chain-like protein that provides strength and some cushioning throughout the body, including the skin. It is collagen that keeps your skin from pulling apart, providing resistance to stress. In addition to skin, collagen is also found in cartilage, tendons, bones, ligaments, and just about everywhere else. Elastin is – as the name suggests – and elastic molecule that allows skin (and other tissues) to return to its original position when it has been deformed. You might think of collagen as chain that has strength and elastin as a rubber band that stretches. Collagen prevents too much deformation, while elastin pulls skin back after slight deformations.

As we age, both of these fail. Collagen breaks and our skin becomes more fragile and prone to damage from slight impacts or friction. Elastin breaks and our skin sags and no longer “bounces back”. As both of these fail over time, we form wrinkles, although these are only one of the obvious cosmetic changes that occur. Skin loses both strength (collagen) and elasticity (elastin) over time. Why?

Whether you are six or sixty, your collagen and elastin molecules are steadily breaking down and failing. The difference is not the rate of damage, but the rate of turnover. This is the rate at which molecules – such as collagen and elastin — are recycled and replaced. In young skin, collagen turnover can be as high as 10% per day, but the rate of turnover falls steadily with chronological age, or more specifically, with cell aging. As cells are lost and replaced by cell division, the telomeres shorten, gene expression changes, and molecular turnover slows down. The older your cells, the slower the rate at which they replace damaged extracellular proteins, whether collagen, elastin, or any other protein (such as beta amyloid in the elderly patient with Alzheimer’s disease). No wonder our skin becomes fragile, loses elasticity, and develops wrinkles.

Despite the advertising world, none of these changes are amenable to moisturizers, protein injections, serums, creams, or a host of other “miracle anti-aging products” that tout the ability to erase wrinkles, rejuvenate skin, and restore lost beauty.

There is, however, one intervention that would be effective: to reset gene expression and upregulate molecular turnover, so that key molecules, such as collagen and elastin, are more rapidly turned over, with the result that damaged molecules no longer accumulate, but are replaced more quickly. The key to extracellular aging isn’t the damage, but the rate of turnover. The practical implication is that whether we are talking about collagen, elastin, beta amyloid, or dozens of other types of extracellular protein, we can effectively intervene by resetting gene expression. Whether we are looking at skin, joints, bone, or brains, the potential is an innovative and effective intervention for age-related problems.

Next Time: 2.9 Cell Senescence And Tissue Aging