and its days are over. Acute trauma and uncontrollable infections will kill an organism without aging that organism. Sometimes the stress inside a cell, such as a multitude of DNA breaks, is too much to handle. Even if the cell is able to repair the breaks in the short term without leaving mutations, there is information loss at the epigenetic level.
Here’s the important point: there are plenty of stressors that will activate longevity genes without damaging the cell, including certain types of exercise, intermittent fasting, low-protein diets, and exposure to hot and cold temperatures (I discuss this in chapter 4). That’s called hormesis.28 Hormesis is generally good for organisms, especially when it can be induced without causing any lasting damage. When hormesis happens, all is well. And, in fact, all is better than well, because the little bit of stress that occurs when the genes are activated prompts the rest of the system to hunker down, to conserve, to survive a little longer. That’s the start of longevity.
Complementing these approaches are hormesis-mimicking molecules. Drugs in development and at least two drugs on the market can turn on the body’s defenses without creating any damage. It’s like making a prank call to the Pentagon. The troops and the Army Corps of Engineers are sent out, but there’s no war. In this way, we can mimic the benefits of exercise and intermittent fasting with a single pill (I discuss this in chapter 5).
Our ability to control all of these genetic pathways will fundamentally transform medicine and the shape of our everyday lives. Indeed, it will change the way we define our species.
And yes, I realize how that sounds. So let me explain why.
ON APRIL 15, 2003, NEWSPAPERS, TELEVISION PROGRAMS, AND WEBSITES around the world carried the story: the mapping of the human genome was complete.
There was just one pesky problem: it really wasn’t. There were, in fact, huge gaps in the sequence.
This wasn’t a case of the mainstream news media blowing things out of proportion. Highly respected scientific journals such as Science and Nature told pretty much the same story. It also wasn’t a case of scientists overstating their work. The truth is simply that, at the time, most researchers involved in the thirteen-year, $1 billion project agreed that we’d come as close as we possibly could—given the technology of the time—to identifying each of the 3 billion base pairs in our DNA.
The parts of the genome that were missing, generally overlapping sections of repetitive nucleotides, were just not considered important. These were areas of the code of life that were once derided as “junk DNA” and that are now a little better respected but still generally disregarded as “noncoding.” From the perspective of many of the best minds in science at the time, those regions were little more than the ghosts of genomes past, mostly remnants of dead hitchhiking viruses that had integrated into the genome hundreds of thousands of years ago. The stuff that makes us who we are, it was thought, had largely been identified, and we had what we needed to propel forward our understanding of what makes us human.
Yet by some estimates, that genetic dark matter accounts for as much as 69 percent of the total genome,1 and even within the regions generally regarded as “coding,” some scientists believe, up to 10 percent has yet to be decoded, including regions that impact aging.2
In the relatively short time that has come and gone since 2003, we have come to find out that within the famous double helix, there were sequences that were not just unmapped but essential to our lives. Indeed, many thousands of sequences had gone undetected because the original algorithms to detect genes were written to disregard any gene less than 300 base pairs long. In fact, genes can be as short as 21 base pairs, and today we’re discovering hundreds of them all over the genome.
These genes tell our cells to create specific proteins, and these proteins are the building blocks of the processes and traits that constitute human biology and lived experiences. And as we get closer to identifying a complete sequence of our DNA, we’ve come closer to having a “map” of the genes that control so much of our existence.
Even once we have a complete code, though, there’s something we still won’t be able to find.
We won’t be able to find an aging gene.
We have found genes that impact the symptoms of aging. We’ve found longevity genes that control the body’s defenses against aging and thus offer a path to slowing aging through natural, pharmaceutical, and technological interventions. But unlike the oncogenes that were discovered in the 1970s and that have given us a good target for going to battle against cancer, we haven’t identified a singular gene that causes aging. And we won’t.
Because our genes did not evolve to cause aging.
YEAST OF EDEN
My journey toward formulating the Information Theory of Aging was a long one. And in no small part, it can be traced to the work of a scientist who toiled without fame but whose work helped set the stage for a lot of the longevity research being done around the world today.
His name was Robert Mortimer, and if there was one adjective that seemed to come up more than any other about him after he passed away, it was “kind.”
“Visionary” was another. “Brilliant,” “inquisitive,” and “hardworking,” too. But I’ve long been inspired by the example Mortimer set for his fellow scientists. Mortimer, who died in 2007, had played a tremendously important role in elevating Saccharomyces cerevisiae from a seemingly lowly, single-celled yeast with a sweet tooth (its name means “sugar-loving”) to its rightful place as one of the world’s most important research organisms.
Mortimer collected thousands of mutant yeast strains in his lab, many of which had been developed right there at the University of California, Berkeley. He could have paid for his research, and then some, by charging the thousands of scientists he supplied through the university’s Yeast Genetic Stock Center. But anyone, from impecunious undergraduates to tenured professors at the world’s best-funded research institutions, could browse the center’s catalog, request any strain, and have it promptly delivered for the cost of postage.3
And because he made it so easy and so inexpensive, yeast research bloomed.
When Mortimer began working on S. cerevisiae alongside fellow biologist John Johnston4 in the 1950s, hardly anyone was interested in yeast. To most, it didn’t seem we could learn much about our complex selves by studying a tiny fungus. It was a struggle to convince the scientific community that yeast could be useful for something more than baking bread, brewing beer, and vinting wine.
What Mortimer and Johnston recognized, and what many others began to realize in the years to come, was that those tiny yeast cells are not so different from ourselves. For their size, their genetic and biochemical makeup is extraordinarily complex, making them an exceptionally good model for understanding the biological processes that sustain life and control lifespans in large complex organisms such as ourselves. If you are skeptical that a yeast cell can tell us anything about cancer, Alzheimer’s disease, rare diseases, or aging, consider that there have been five Nobel Prizes in Physiology or Medicine awarded for genetic studies in yeast, including the 2009 prize for discovering
