The Doctor Weighs In

By Dov Michaeli MD, Ph.D

Yesterday, we posted an article about hyaluronic acid (Restylane, Juvederm) and the incredibly simple, but medically extremely important solution to facial wrinkles. Let me recapitulate:

· As part of the aging process, skin cells called fibroblasts assume a rounded shape and stop making collagen, the protein that constitutes the main bulk of the skin, or dermis.

· At the same time, and enzyme that breaks down collagen, called collagenase, continues degrading the existing dermal collagen. This eventually results in collapse of the dermal architecture—and wrinkles ensue.

· The non-surgical solution to the problem was straightforward: inject more collagen into the dermis to occupy the space under the wrinkle. The problem: collagen gets resorbed, through the action of collagenase, within a relatively short time (3-6 months).

· The recent introduction of hyaluronic acid injections, a normal component of the dermis, changed the game: in addition to simply filling the space, it also caused the fibroblasts to resume the synthesis of collagen. This biological feat was accomplished by causing the fibroblasts to assume their youthful stretched configuration. After a few injections at 6-12 months intervals, the fibroblasts filled the space with newly synthesized collagen.

Why is it revolutionary?

Today’s medical holy grail is to mimic what a lizard can do effortlessly: regenerate a missing, or diseased tissue or organ. So far this has eluded the best minds in medical research. There are several organs that are self-renewing; for instance, the cells of the lining of the gut are constantly shed and new cells take their place. Same for the epidermis. Same for blood cells. But get a deep cut, and the old injured tissue is not replaced with a newly synthesized one—it is replaced with scar tissue. Heart muscle killed by a heart attack is not replaced with new heart muscle—again, it is replaced with scar tissue. The goal of replacing old tissue with a new one that mirrors the original, depends on mastering the art and science of raising stem cells that would give rise to the desired tissue. This is a tough proposition, scientifically and politically speaking. Many laboratories, and billions of dollars of investment have yet to show tangible results.

And yet, using a low tech approach of simply injecting a component of the dermis, the existing old fibroblasts were coaxed into rejuvenating themselves and resuming what they used to do in their youth: synthesize new collagen. No fancy stem cells needed—just good old hyaluronic acid.

Let me hasten to say that this is in no way a substitute for the eventual use of stem cells. But I can’t help but wonder if aging, or damaged neurons could not be coaxed into rejuvenating themselves by injecting some brain matrix material. You can bet on it that right now somebody is already toiling in his laboratory, trying to achieve just that.

The next step

Hyaluronic acid gets degraded in the skin by an enzyme called hyaluronidase. So it is a question of time, even with all the chemical wizardry known to us, before it is broken down and resorbed. Hence the need for new injections every 6-12 months.

The obvious answer to this problem would be to synthesize material that does not get broken down by enzymes.

Last February, a new material was introduced in the market that promises to do just that: withstand the degradation of skin enzymes. The material, ArteFill, is composed of synthetic material that is shaped like microspheres. As the name suggests, these are indeed microscopic spheres, and what they are apparently doing is fill in the space and coax the old fibroblasts to start synthesizing new collagen. The difference from hyaluronic acid is their remarkable longevity; the company is applying to the FDA to extend its approved life in the skin from one year to five years! This is remarkable.

So there you have it; a semi-low tech solution to what is probably a vanity ‘problem’, but of profound biological significance.

If necessity is the mother of invention, then the aging baby boom generation is already unleashing a remarkable revolution in the biology of longevity and the medicine of aging. I can’t wait; in fact, I can’t afford to wait.

Dov Michaeli MD, Ph.D. is in the Biotech industry, and is in dire need of anti- aging medications.