Will Geroprotectors Extend Lifespan to 150+ Years?
By now, just about everyone knows that geroprotectors and other life extension treatments (LETs) can extend the lifespans of model organisms such as mice. Examples include metformin [1, 2], rapamycin [3, 4], calorie restriction [5, 6], resveratrol [7, 8], and NAD+ precursors [9, 10]. The number of PubMed publications and Google searches has been increasing exponentially for many specific LETs.
What many may not know, though, is that there aren’t just a handful of these LETs. There are actually thousands of LETs that have emerged over the last hundred years, which is around the time that life extension in mice was first discovered . And between 1950 and 2000, hundreds of diets, molecules, exercises, and other interesting methods, were discovered to extend mouse lifespan.
For some odd reason, it took a long time for the public and our healthcare system to become aware of all of this [12-20]. Although the topic is now popular, not one time did I learn about extending organism lifespan or reversing aging during the time I spent as a biomedical undergrad.
That changed my last semester, when I watched some YouTube videos of Dr. Aubrey de Grey, Ray Kurzweil, and Dr. Martine Rothblatt [21-23]. After watching the videos, I asked my colleagues and professors about the topic. Somehow, not a single one of them had heard of this seemingly promising research. Not even the gerontology department had heard of it.
I hope one day to discover the reasons behind this historical lack of awareness. But, for now, there's no time. The research must be developed!
Brief History of Life Extension Research
It was not until around the beginning of the 21st century that we began to see genetic edits extending the lifespan of model organisms [24-30]. One life extension gene edit after another was discovered as the years went by.
Before we knew it, hundreds of different genetic edits had extended mouse lifespans. Hundreds more had extended the lifespans of other model organisms. And their health-spans were dramatically increased also.
Single genes were deleted or over-expressed to extend the lives of mice by up to 50% [31-35]. Diets [36, 37], small molecules [38, 39], and other interesting approaches [40, 41] were discovered. And adult stem cells extended mouse lifespan between 10% and 35% .
Recently, Dr. Nir Barzilai began planning a human clinical trial (TAME) using metformin to target age-related diseases . It could be one of the greatest trials ever conducted. Metformin won't necessarily extend human lifespan exactly as we’ve observed in model organisms [1, 2]. But this may trigger an avalanche of new research by massive biotech companies with the goal to help us live healthy lives up to 150 years or longer.
Direction of Life Extension Research Today
Imagine an industry in which thousands of diets, drugs, supplements, genetic edits, and stem cells are tested and combined for optimal healthy life extension. It could be as simple as a quick injection for gene therapy. Or maybe we could consume a combination of strawberries and green tea for the fisetin  and EGCG . This is the direction that LETs are going.
Only a few scientists have been bold enough to combine multiple LETs in tests on model organisms [46, 47]. In 2019, Dr. George Church and his research team published a spectacular paper. It described the results of making three genetic edits with a single gene therapy combination in mice .
Dr. Church didn't take time to measure life extension in the mice because he thinks that measuring life extension in humans will take too long. Imagine a forty year trial! To prove life extension in humans, we would have to live far longer than 120 years. Instead, Dr. Church believes we must focus on preventing and reversing parameters of biological aging because we can measure them faster.
So he and his team targeted four age-related diseases in mice. It wasn’t too surprising that their health-span increased. And their biological aging process slowed compared to controls. In other words, the mice remained youthful for much longer.
And why would he stop there? His plan is to test a combo treatment of gene therapies in dogs. It will contain not three, not four, but over forty of promising gene therapies .
Speculating on the Potential of Life Extension
In yeast, flies, and nematodes, single LETs can extend lifespan well over 100% [50, 51]. And many single LETs can extend mouse lifespan by 20% to 40%.
Let's do some speculative math. Assume we observe in mice at least a 10% increase in maximum lifespan from each of 45 gene therapies. 45 times 10% equals a 450% increase in lifespan.
If that translated over to humans, we would live longer than 400 years. And we may even be healthier than today’s healthiest 25-year-olds.
However, some studies have indicated that combinations aren't synergistic. For example, if two treatments extend mouse lifespan by 10% each on their own, we might observe an increase of about 15% from the combination.
So, backing off, imagine a 200% life extension in humans from something as simple as just drinking enough green tea, injecting a few stem cells, and applying some gene therapies. Should we believe this is possible?
Are humans too complex? Do humans live too long? Well, mice are much more complex and live much longer than nematodes. And we have observed 20% increases in mouse lifespan from treatments that only extend nematode lifespan by 10% [52, 53].
So the complexity argument doesn’t always work. And, at the end of the day, we might as well check how thousands of model organism studies translate over to humans. Let's not rule out possibilities until we've properly tested them. We should conduct more human trials like TAME, but with combinations of LETs.
Lifespans of 150 years would be less than a 50% increase in maximum lifespan for humans. Maybe it will only take a few LETs to help us all get there. And there are hundreds of promising LETs to explore.
Why only 150 years? Have we already discovered a method to keep people alive, as some enthusiasts describe it, "long enough to live forever"? In other words, do we already have the tools we need to survive just long enough to make better tools, over and again, and achieve longevity escape velocity?
We spend trillions of dollars targeting symptoms of specific diseases. But, right in front of our face, we might already have a relatively inexpensive method to achieve what our ancestors have hoped for millennia. Maybe we can finally, once and for all, put an end to suffering and death from aging!
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