The timeline of the human condition is simple. We live in the womb for 9 months, grow up to be infants and teenagers, transition into adulthood, and then we pass away. Everybody knows this is the pathway of our lives. In Canada, the average time this all takes (life expectancy) is 80 years for men and 84 years for women. Not a short amount of time, but what if we could extend or even reverse this aging process?
New research published in the journal Cell shows that by tweaking gene activity we can reverse and slow down the aging process in mice and human skin cells. To understand the ramifications of this study, we must first understand the aging process.
What is aging?
This question seems simple enough. We are born, we grow up, and our bodies age and break down. But what is going on at the molecular level to cause us to age? And better yet, why do we age anyway? Wouldn’t it be better if we were immortal? Let’s start with why we age.
One of the main downfalls of immortality would be resource availability. Think about it for a moment. With billions of people on Earth already, there are countless people running out of food.
In addition to this, some regions are overpopulated. This is with 7 billion people. If every human who has ever lived was still on Earth, there would be 108 billion people sharing this planet! Clearly, not enough room or resources.
So, evolution has decided that humans need to die after a certain amount of time. But, wait a minute. If evolution is so smart, shouldn’t it allow the fittest humans to survive forever so that they can keep reproducing? Although this may make sense, it is an over-simplification of the idea.
The most widely accepted reason for why we age in the first place is this:
to give people the best chance of surviving until the age of reproduction, we also need to turn on certain genes that cause us to break down.
Of course, there is some concrete evidence to support this theory. Nearly every organism on Earth ages and eventually dies (not all of them though!). It’s the circle of life. Whatever caused aging to occur at the beginning of biological life hasn’t changed its mind in billions of years, and likely won’t anytime soon.
The Physiological Process of Aging
We know why we age, but how does it occur? There are two main pathways that explain how we age: programmed aging and damage accumulation.
Let’s start with programmed aging. Programmed aging is the inherent process that occurs after natural growth and development. As you might have guessed, this process is very reliant on our genetic makeup. Certain genes turn on and off. This result in the differential expression of various maintenance and repair mechanisms.
Different species age at different rates. Think of 100-year-old trees. These differences in age progression are due to the species respective genetics (something we hope to harness one day). When it comes to programmed aging, there are a variety of pathways that have been identified. One of the most extensively studied is known as telomere shortening.
First off, what are telomeres? Humans have 23 pairs of chromosomes. At the end of every chromosome, there are short sections known as telomeres. When cells divide and grow, (due to chromosome duplication) the enzyme controlling this process does not reach to the very end of the chromosome. Because of this, after every single replication cycle, our chromosomes shorten. Eventually, the chromosomes reach their Hayflick limit. The number where cells can no longer divide. Researchers are looking at ways to halt this shortening process in its tracks. Stopping the shortening could effectively stop aging.
At this time, scientists haven’t harnessed the power of telomeres in humans. But researchers have been able to reverse the aging process and increase lifespan in lab mice.
The second aging pathway concerns DNA damage accumulation. Researchers believe DNA damage is likely the single most important cause for aging. Throughout our lives, our bodies take a beating. Cuts and bruises we see, but the beating our DNA takes is just below the surface.
Over time, our DNA damage from harmful chemicals, diseases, and reactive oxygen species. This can lead to harmful DNA mutations, altered gene expression, and genetic instability. Sometimes, the DNA damage is so severe that apoptosis (programmed cell suicide) can initiate. Again, the accumulation of DNA damage is completely natural. Unfortunately, it is completely out of our control.
Manipulating our Genes
The study published in Cell aimed to reverse the aging process in a different way: by altering the genes that drive the aging process forwards.
In this investigation, the researchers were working with 4 genes known to be associated with the aging process. These 4 genes are known as the Yamanaka Factors, named after the scientist who discovered them. By tweaking these 4 genes, the scientists were able to transform adult cells back into their embryonic state. This not only shows that the aging process slowed down, but that it was actually reversed.
But this method isn’t without some risks. The study found that when some mice developed tumours and died within a week with continuous treatment. But mice survived with shortened treatment.
The same idea applies to telomere shortening. Although stopping telomeres from shortening may lengthen lifespan, this is the exact mechanism by which cancer cells survive. Approximately 80% of cancerous tumours express the enzyme telomerase, which stops the shortening process. By this mechanism, cancer cells become immortal.
Thus there’s a fine line we must tread in our search for immortality, as it may lead to our demise. Nonetheless, studies like the one in Cell have a profound impact on man’s search for the ever-elusive fountain of youth.
Life Extension
One of the main goals of humanity is to increase life expectancy and may be one day become immortal. We already managed to see a dramatic increase in the human lifespan with advancements in medicine and technology. In the last 100 years, we raised the global life expectancy from 31 in the 1900’s to 67.2 in 2010.
We’re on the upswing, and lifespan will only swell more and more as society evolves. Here are some of the more intriguing life-extension strategies of the future.
Calorie Restriction
Now this one is interesting. Caloric restriction is the most common anti-aging strategy currently in use. It involves restricting our diet to our basic needs. We eat only as many calories as we need without leading to malnutrition.
In this strategy, we aren’t losing any of our essential nutrients, but getting rid of all the calories we don’t need. Although it may seem rather rudimentary, the results are fascinating.
Caloric restriction can increase median and maximum lifespan and can slow the aging process in rodents, fish, and dogs. There are a multitude of mechanisms by which this strategy works, but, long-term results in humans have yet to be identified.
Anti-aging drugs
Calorie restriction doesn’t sound too fun, does it? How about taking a pill that mimics its effects without any of the diet restrictions? This is the goal of calorie restriction mimetic drugs.
The main goal of these drugs is to target the same pathways that caloric restriction influences. Some drugs studied and used in lab animals include metformin and rapamycin.
Anti-aging drugs aren’t only looking at calorie restriction pathways. Coming back to telomeres, drugs are being developed that could activate telomerase.
As we now know, telomerase stops the telomere shortening process and stops aging. However, these drugs need to be vetted carefully because of telomerase’s capacity to induce cancerous tumours.
Cloning and Transplantation
The fields of gene therapy and stem cell research are running on all cylinders at the moment. With targeted gene therapy, we could, in theory, identify the genes associated with aging and turn them off (think back to the Cell study).
By isolating our own stem cells, we could grow new organs in the laboratory. Need a kidney transplant? Scientists could harvest your stem cells, grow them in a dish to make a kidney, and insert it back into your body without any of the harmful effects of organ-rejection. No more waiting lists; you are your own perfect match.
Of course, the use of stem cells and organ generation open up Pandora’s Box of ethical concerns (see Ewan McGregor’s 2005 film, The Island). Nonetheless, stem cell research and gene therapy are paving the way for a whole new world of biomedical possibilities.
Perhaps one day we may even reach biological immortality. It is possible. Just ask the immortal jellyfish Turritopsis dohrnii.
