Exercise Mimetics: "Exercise in a pill"
Here’s a thought experiment -?
If I were to hand you a pill that did the following:
*note all these resemble age-related physiological changes*
Would you take it? Probably not… Well, exercise does all this and more and yet regular exercise is one of the most important things anyone can do to improve their health. Regular exercise is associated with the reduction in risk of age-related diseases (cardiovascular disease, diabetes, cancer neurodegeneration). Furthermore, degree and frequency of exercise are largely considered the most influential factors in the development and progression of the conditions that kill the majority of US adults over the age of 40.
But how do we come to terms with this paradox??
Well for the most part, it’s not necessarily the exercise itself that infers resilience to disease but the recovery mechanisms that follow. This is the concept of “hormesis” - where intermittent?exposures to a?limited stressor (such as exercise, hot/cold therapy, intermittent fasting etc) promote long lasting beneficial adaptations.
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In this framework, we could consider routine exercise as an intermittent and limited exposure to aging-like stress which eventually leads to increased resilience to such processes and consequently age-related diseases.?
However, the only difference between a treatment and a poison is the dose. Luckily, human nature ~for the most part~ is self-limiting with regards to the dosage, and it takes extreme motivation to push beyond what would be considered beneficial (i.e., “overdose” on exercise or “overtrain”). The downfall is that exercising is not the default, and our modern environment has evolved in a way where ~for the most part~ it is no longer necessary in daily living and even requires time and money to do so.
So, can we “supplement” exercise for those who are deficient??The answer here is probably unsatisfactory, but somewhere between yes, no, and kind of.?
According to several recent studies, it is possible to capture some of the benefits of exercise by supplementing signaling molecules secreted during physical exercise. Such treatments are called “exercise mimetics,” an emerging therapeutic modality focused on enhancing or mimicking the beneficial effects of exercise. However, the list of targets and molecular pathways for exercise mimetics is exhaustive and growing daily, as is the conceptualization of potential drug combinations and dosing regimens.?To date, the primary focus for such interventions has been those who are unable to exercise due to disability and military personnel, as well as patients in recovery who could benefit from exercise but are at risk of further injury.?
Similar to most emerging fields, the field of exercise mimetics is not without its challenges and controversies. Although physical exercise is largely self-limited by exhaustion, this safeguard is not extended to “exercise therapeutics,” which could be abused or taken improperly, which would skew the hormetic balance toward “chronic stress,” doing more damage than is repairable.?
In summary, I think the efforts and resources pouring into exercise mimetics only validate the undeniable benefits of physical exercise, which is readily accessible for most here and now. The “3-mile jog” pill may not be too far-fetched and may come sooner than anticipated as scientists and physicians parse out the nuances of this convoluted hormetic mechanism.
More to come on specific studies and drug candidates.?