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Aging is my primary area of research and in our lab we study what causes aging and how to slow it down. Our goal is not to make anyone live to 130, but rather to increase the period of time one spends healthy and compress the period of time spent in an age-related decline. There are many theories about how and why aging occurs. These various theories have different viewpoints from cellular function to evolutionary rationalizations. All these theories have merits and set a vantage point for the particular line of hypothesis testing. This column will explain a very simple theory and then explain why physical activity, such as cycling, helps slow the aging process.

One very simplistic way to think about aging is that it is the accumulation of damage over time. This accumulation of damage reduces the function of cells and tissues, thus resulting in even more damage. For the sake of analogy, think of something you own that gets repeated use – bike, car, refrigerator, carpeting – and it is easy to imagine how prolonged time leads to accumulated damage. However, the difference with these examples compared to your body, is that these inanimate objects don’t have integrated processes that are supposed to prevent damage from occurring in the first place or repair them when they happen. Why is it that the human body has processes in place to prevent damage but even this fails over time?

Our bodies have to constantly adjust to the environment around them whether that be heat, cold, solar radiation, invaders (viruses and others) and energetic stresses. When the body adjusts correctly, it makes the body stronger and more resistant to these environmental changes. When the stresses are extreme, there is maladjustment in the body and these stresses can be damaging. I’ve mentioned this concept before (called hormesis), which refers to the idea that a little stress is good and strengthens the system whereas too big of a stress is maladaptive and damaging. If you consider that aging is a very slow decline over time, you might view the accumulation of damage the cumulative maladaptation over time. However a damaging event does not always have to remain in the physiological record of an individual if it can be efficiently repaired.

Now let’s consider how physical activity benefits cellular structures. Recall that I said that the adaptation to a low dose stress in the body strengthens the cell to subsequent challenges. Think of endurance exercise as a low dose energetic stress. This stress forces the cell to adapt in order to supply and use energy better to avoid future stresses. This adaptation process requires the making of new proteins, since the proteins are what provide resistance to future stresses. In that sense then, exercise is always adding new proteins to the system. However, equally important to the making of new proteins is the breaking down of old ones. Your cells do not like to keep extra proteins around that are not needed because it is costs a lot of energetic currency to keep them running well. Therefore, the making of new proteins is usually accomplished by the breaking down of old proteins, or what is referred to as turnover or remodeling.

How does physical activity, such as cycling, slow aging? There are two primary ways physical activity is beneficial – preventing damage in the first place, and repairingdamage after it occurs. The making of new proteins and breaking down of old proteins is key to both preventing and repairing damage. First, physical activity synthesizes proteins that make the cell stronger, thus being less susceptible to damage. Second, if damage does accumulate, physical activity accelerates the making of new proteins and breaking down of old ones in order to rid the cell of damaged structures and replaces them with new ones. Therefore, exercise is both a preventative maintenance to the aging process and a repair process for some of the effects of aging that have already occurred. 

Although in concept this all sounds super easy to understand, the genetic, molecular, and cellular processes that control this making and breaking down of proteins is decidedly complex. There are multiple points of regulation and multiple pieces of information, which are often at odds with each other, that are constantly integrated to make decisions about the making of proteins and cellular fate. For example, think about the age-related disease of cancer, the cell is getting signals to continue to replicate and grow (tumorigenic), while other signals are trying to prevent that from happening (anti-tumorigenic). How the cell makes that choice is what we strive to understand.

We know that exercise is a very potent stimulator of protein turnover and thus cellular maintenance and repair. At this point, physical activity is probably the most effective slowed aging treatment there is because no drug has been able to recapitulate the protein quality control mechanisms that exercise activates. When I am asked if the research in our lab has produced any breakthroughs to slow the aging process, I am forced to admit that we already know what works (exercise), we just don’t know enough about how it works. We continue research into learning how it works so we can understand better how to take advantage of those processes for human health. Because, as we are all too familiar with, exercise is not as popular as we think it should be.