Aging is Driven by Overachievers

Healthy Aging

Rapamycin & the hyperfunction theory of aging

There have been many advances in science around aging – and ideas on how to slow it. While anti-aging used to be an area limited to anti-wrinkle creams, some of the smartest researchers at the most prestigious institutions are pursuing the fountain of youth. Well, at least a drinking fountain that will keep us healthier longer.

This series of Science Says, inspired by a feature in GEN Biotechnology, is dedicated to the most promising advances in longevity research – and popular concepts that have recently fallen. This week, let’s talk about one of the most promising anti-aging candidates: rapamycin.

What is rapamycin?

Here’s a great origin story you can share over Thanksgiving dinner this week: Discovered on Easter Island back in 1972, rapamycin is a molecule made by the bacterium, Streptomyces hygroscopicus. It got its name from the original name of Easter Island – Rapa Nui. The “mycin” part of rapamycin comes from its initially discovered role as an antifungal compound.

Available only as a prescription drug, rapamycin is approved by the FDA to help prevent kidney transplant rejections, for treating a lung disease called LAM, and for treating angiofibromas, which are facial bumps that can occur in people with a condition called tuberous sclerosis.

Killing fungi, saving lungs and kidneys, and removing facial bumps…oh my! How exactly does rapamycin work?

While rapamycin was originally characterized as an immunosuppressant, it seems to behave more like an immune modulator. That means rapamycin helps our immune system behave the way it should – without over or under reacting. Rapamycin also helps to stop fibrotic cells from proliferating, which prevents damaging scarring of tissues, including lungs. This anti-proliferative effect explains rapamycin’s anticancer properties, too. Rapamycin’s immune-modulating and anti-proliferative effects are due to its role as an mTOR inhibitor. And this is where rapamycin’s longevity potential comes into play.

When a longevity pathway is named after you, that’s when you know you’ve got promise.

Okay, let’s start with explaining mTOR. It stands for mammalian Target of Rapamycin. So yeah, it’s what rapamycin targets. The mTOR pathway is like that kid who goes crazy during their first year in college without parents around. In short, mTOR encourages cells to be out of control. And rapamycin is the parent who gets those cells back into shape – before your future is ruined.

Rapamycin and the hyperfunction theory of aging.

When we think of aging, we often think of slowing down. Aging, however, comes with a fascinating paradox. Instead of slowing down with age, our cells speed up.

In the journal Cell Cycle, Blagosklonny describes how our cells hyperfunction as we get older. It makes sense, right? Hypertension, hypercholesterolemia, system-wide inflammation, and overgrowth of cells that cause cancer. This hyperfunction is caused by growth-promoting pathways, including mTOR and MAPK. Thus, if we can figure out how to calm these overachieving cells, we can help slow the aging process.

This cell-calming function of rapamycin explains why it is so promising as a longevity drug. In numerous models, including worms, flies, and mice, rapamycin has substantially increased longevity. While studies are still needed to see if rapamycin can help humans live longer and healthier, Blagosklonny urgently pushes for the advancement of rapamycin to support our longevity. In his paper published in the journal, Aging, he includes the quote:

“If you wait until you are ready, it is almost certainly too late.”

– Seth Godin