Rapamycin: The miracle chemical discovered in Easter Island’s dirt
Our bodies are quite miraculous machines and as a whole, we are near perfect. We are born with a genome that contains the code for every protein necessary for survival. We develop, produce hormones that allow us to reproduce, and have children. Then we all grow old.
But what exactly happens as we get older? This question has puzzled scientists for years while they offer theory after theory.
In 1957, evolutionary biologist George Williams proposed what he called the antagonistic pleiotropy hypothesis as a theory of how and why we age. He claimed that our bodies will express a gene that has benefits for our early life, even if that same gene will harm us later on. His hypothesis has inspired aging research since, leading us to a story about a chemical discovered deep within the dirt of an island floating in the Pacific.
From dirt, potential
In 1964, Canadian researchers led by Stanley Skoryna from McGill University set sail out of Halifax for Easter Island, a speck of land floating 2,000 miles off the coast of Chile, where human population is small but life is diverse. They were hoping to retrieve precious specimens from the island before its land was tarnished with the building of a new airport. Stanley and his team collected hundreds of plant samples, countless animal specimens, and took blood and saliva from all 949 of the island’s residents.
What they found buried in the dirt of Easter Island would turn out to be the biggest treasure of all: a bacteria that would mystify scientists for the next 50 years.
This bacteria was found to create a chemical now known as rapamycin, cleverly named after Easter Island’s native name, Rapa Nui.
Rapamycin’s life-prolonging properties
Since its discovery, research teams have worked tirelessly to show that rapamycin can actually extend the lifespan of laboratory mice. The importance of this finding lies in the fact that it increases maximum life span, not just average lifespan, for other drugs have been claimed to do this. Rapamycin is one of a kind in this way, extending lifespan in already-old mice by a third.
Rapamycin’s discovery has led to other quite amazing implications in medicine, being used to treat yeast infections, to inhibit cancer growths, to treat various cancers, and to aid in the recovery of kidney transplant patients.
Research surrounding rapamycin has also led to discovery of the target of rapamycin (TOR) pathway. TOR is simply a protein and its related gene that rapamycin targets. Its pathway has been associated with age-related diseases like cancer, Alzheimer’s, Parkinson’s, type-2 diabetes, and osteoporosis.
Unfortunately, we can’t give rapamycin to humans in quite the same way scientists have with mice. The chemical shows side effects that inhibit us from testing it on ourselves. The discovery of the TOR genes has opened a new door, one that shows scientists where to send drugs for age-related diseases.
Scientists demonstrate that Target of Rapamycin is a nutrient sensor
Here’s how it works: We eat, sparking TOR activity, promoting cells to grow and divide, producing proteins that our bodies need. We stop eating, and these processes settle down to conserve energy; TOR activity slows, so does cell growth and division. At the same time, autophagy starts to kick in – our cells rid themselves of all the built up garbage they accumulate with time. Food comes back, and the process starts all over again.
Let’s use type-2 diabetes as an example. It turns out that insulin, an important hormone released by the pancreas, is related to the TOR pathway. Overeating triggers near-constant TOR activity, making cells less sensitive to insulin when it is released. Eventually, cells become resistant to insulin levels, leading to detrimentally high blood sugar levels and causing things like diabetes and heart problems.
How is this process relevant to age-related disease?
Scientists have known for years that calorie restriction extends lifespan. In 1935, nutritionist Clive McCay of Cornell University showed that putting young rats on near-starvation diets made them extremely long-lived. Similar studies have been done on our closer relatives, monkeys. Cutting their calorie intake by a third in early life has shown a boost in maximum lifespan by 30 to 40 percent. However, we can’t just starve ourselves.
In the early 2000s, scientists discovered that this calorie restriction might be mimicked by genetically suppressing TOR synthesis; that is, turning its activity down. It suggests that aging, thought to be an extremely complex science, might be slowed by altering one single gene.
One of the most influential theories surrounding TOR and calorie restriction process comes from Mikhail Blagosklonny, a former cancer researcher at the Roswell Park Cancer Institute in Buffalo, New York. His theory proposes that TOR, whose pathway is essential for development and reproduction in mammals, becomes the driving force behind aging once we have reached maturity. His paper published in Aging 2009 reads: “Life-promoting TOR signaling seems also to contain seeds of death.”
This brings us back to George William’s explanation of aging – that our bodies depend on one protein for our survival, and that same protein causes aging and death later in life. In other words, aging is caused by a ‘two-faced gene’ that is beneficial early in life, and harmful later on.
Mimicking the effects that rapamycin has on mice could, scientists propose, add five to 10 years to human life. Boosting life expectancy this much will require us to tackle age-related diseases that are becoming more and more prevalent. Scientists say we must find drugs to combat these diseases; drugs that promote healthy living, not just longer living.
- In response to Rapamycin Press’ blog post about the history of Rapamycin and its discovery, Derek asks: So, a gene that are essential for my body’s development could potentially be detrimental later on in my life?
- Yes. This theory, first proposed by George Williams, has been elaborated on in more recent research. To some scientists, it’s a good explanation as to why and how our bodies age. For example, it explains why testosterone is key in development of men, while its levels can cause prostate cancer later in life.
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