Newsletter #288

You no doubt already know that physical exercise is good for various dimensions of health, like your metabolism, your bone strength, your immune system, even your brain. But what about your skin?

I remember a while back I came across a paper examining how mitochondrial function, which deteriorates with age, influences skin health. The researchers compared mitochondrial energy metabolism in human skin samples from young and old donors, and found that the older samples had reduced expression of key mitochondrial proteins. Maintaining robust skin demands energy, which is manufactured by the mitochondria in our skin cells. It’s not hard to imagine how impaired bioenergetics in our skin could lead to deleterious changes in the structure of our skin, and ultimately manifesting in visible signs of aging, like wrinkles, sagging, etc.

The research team goes on to speculate about compounds that could enhance ATP production to counter this phenomenon (including our old friend creatine). However, the most reliable way to enhance mitochondrial biogenesis in the body is exercise. And of course, exercise has other beneficial systemic effects, like dampening inflammation, which you might expect to improve parameters of the skin. Let’s take a look at what research shows on this question.

To examine the endocrine effects of exercise on skin, researchers in Ontario performed a series of experiments. First, they compared the skin structure of highly active adults to sedentary controls across various age groups. They found that the exercisers had greater mitochondrial content in their skin, and reduced signs of physiological aging.

But of course, you can imagine all kinds of reasons why a group of people who regularly exercise more than 4 hours per week might have more youthful skin than people who don't work out at all. Maybe they have healthier lifestyles overall, and better skincare routines? To put it to the test, they enrolled sedentary elderly adults in a 3-month exercise program (cycling) to see what happens to skin parameters when you add a dose of exercise. Sure enough, they found that 12 weeks of exercise increased collagen content of the dermis, as well as skin mitochondrial content.

Next, they wanted to figure out what was driving this mitochondrial response to exercise at the molecular level. They drew serum from some of the participants from the cross-sectional study (both sedentary and active) before and after exercising, and incubated human skin cells in the extracted fluid. They saw increases in mitochondrial content in these skin cells, but only in response to serum that had been extracted from the athletic subjects post-workout. So clearly some kind of circulating factor, elicited by exercise, was responsible. Further screening and chemical analysis revealed that interleukin-15 was causing the mitochondrial changes. IL-15 is a cytokine released by skeletal muscle cells (also known as a myokine), and a possible mediator of some of the health benefits of exercise, though this is the first time it's been linked to skin health.

For a little more insight into the role of IL-15 in this signaling cascade, the researchers performed some animal experiments. When they had mice run on a treadmill, they observed that Pgc-1α, a key regulator of mitochondrial biogenesis, rose in both muscle and skin, and this was accompanied by an increase in serum IL-15. Finally, intravenous injections of IL-15 in rodents, in doses that mirrored the natural increase in IL-15 in response to exercise, effectively mirrored the anti-aging effect of exercise, leading to increased mitochondrial content in the skin, as well as dermal collagen.

IL-15, along with other myokines, normally rises transiently by about 5-fold in response to exercise for about an hour or so before returning to resting levels. The researchers suggest that repeated pulses of IL-15 following bouts of exercise, over time, leads to remodeling of the skin and prevents age-related tissue degeneration. Seems like a good argument for frequent workouts.

As previously noted, many of the health benefits of exercise are attributable to myokines. However, aerobic training and resistance training have been shown to exert different effects on circulating levels of various factors, including the aforementioned IL-15. So how do these types of exercise affect skin aging? Is one better than the other?

To compare their effects, Japanese researchers recruited 61 healthy sedentary middle-aged women, and evenly split them into two groups, one of which performed aerobic exercise and one which engaged in resistance training. They trained twice per week for 16 weeks under the supervision of athletic trainers. Before and after the intervention, subjects gave blood samples, and various properties of their skin were analyzed.

Both groups observed improvements in overall health, as well as skin structure. Notably, skin elasticity was boosted in response to both resistance training and aerobic exercise. However, the resistance training group saw some additional benefits. Resistance training resulted in increased dermal thickness, a key anti-aging effect (the dermis gets thinner with age, and this change in underlying structure significantly affects how the skin looks).

To better understand underlying mechanisms, the researchers took plasma from participants, both before and after training, and cultured the samples with human skin cells. For both groups, plasma extracted after exercise elicited increased expression of genes that code for proteins that make up the extracellular matrix of the dermis, like collagen. That would certainly explain the overall improvements in upper dermal structure.

After resistance training, the researchers noticed that expression of biglycan increased. Biglycan is a protein found in the dermis, which has been shown to decrease with aging and with sun exposure. Mice with a mutation that disables activity of the gene that codes for biglycan have a thinner dermis, so perhaps this was why resistance training boosted dermal thickness. This appeared to be due to changes in circulating inflammatory factors specific to resistance training.

Although resistance training seems to have the advantage here from an anti-aging standpoint, it's likely that both modalities are beneficial in slightly different ways. When the researchers compared blood work from both groups, they observed a range of differences in circulating factors. Notably, IL-15, the myokine responsible for the improvements in skin bioenergetics from the prior study, only rose in response to aerobic exercise, not resistance training. So, if you want optimally healthy and youthful skin, performing a mixture of both training types, much like the guidelines recommend, is probably the right way to go.

💄 Women used lead-based makeup for thousands of years.

People go to extraordinary lengths in pursuit of beauty even today, and sometimes to the detriment of their health. But fortunately, rigorous safety testing has enabled us to more clearly identify truly hazardous exposures. Cosmetics, especially, have become much safer. For example, up until around the 19th century, it was not uncommon to use makeup that incorporated lead carbonate, which was prized for its beautiful white pigment (also used, infamously, in paint).

It’s worth noting that a lot of these cosmetic formulas probably were not quite as toxic as you might expect. The outermost layer of your skin is a pretty robust barrier, and the extent to which a given topical product absorbs into the skin depends on an array of factors.

Queen Elizabeth I is thought to have used a formula of lead carbonate mixed with vinegar known as Venetian ceruse, and modern analysis suggests that this would have been a particularly dangerous combination due to the acidity of the vinegar. Perhaps even worse, she is said to have worn a red lipstick infused with mercury.

Note from Dan: I learned about this product from my friend Donna Stone, a Master Trainer at Therabody University, while working with the US Special Forces. This product combines warmth, sound, and vibration to lower heart rate and relax. Indeed, wearing it is quite pleasant and relaxing.

Here is more information about the product from their website:

https://mailchi.mp/humanos.me/newsletter-288