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a misconception that cloned animals age prematurely. It has been widely perpetuated in the media and even the National Institutes of Health website says so.¹⁹ Yes, it’s true that Dolly, the first cloned sheep, created by Keith Campbell and Ian Wilmut at the Roslin Institute at the University of Edinburgh, lived only half a normal lifespan and died of a progressive lung disease. But extensive analysis of her remains showed no sign of premature aging.²⁰ Meanwhile, the list of animal species that have been cloned and proven to live a normal, healthy lifespan now includes goats, sheep, mice, and cows.²¹

      Because of the fact that nuclear transfer works in cloning, we can say with a high degree of confidence that aging isn’t caused by mutations in nuclear DNA. Sure, it’s possible that some cells in the body don’t mutate and those are the ones that end up making successful clones, but that seems highly unlikely. The simplest explanation is that old animals retain all the requisite genetic information to generate an entirely new, healthy animal and that mutations are not the primary cause of aging.²²

      It’s certainly no dishonor to those brilliant researchers that their theories haven’t withstood the test of time. That’s what happens to most science, and perhaps all of it eventually. In The Structure of Scientific Revolutions, Thomas Kuhn noted that scientific discovery is never complete; it goes through predictable stages of evolution. When a theory succeeds at explaining previously unexplainable observations about the world, it becomes a tool that scientists can use to discover even more.

      Inevitably, however, new discoveries lead to new questions that are not entirely answerable by the theory, and those questions beget more questions. Soon the model enters crisis mode and begins to drift as scientists seek to adjust it, as little as possible, to account for that which it cannot explain.

      Crisis mode is always a fascinating time in science but one that is not for the faint of heart, as doubts about the views of previous generations continue to grow against the old guard’s protestations. But the chaos is ultimately replaced by a paradigm shift, one in which a new consensus model emerges that can explain more than the previous model.

      That’s what happened about a decade ago, as the ideas of leading scientists in the aging field began to coalesce around a new model—one that suggested that the reason so many brilliant people had struggled to identify a single cause of aging was that there wasn’t one.

      In this more nuanced view, aging and the diseases that come with it are the result of multiple “hallmarks” of aging:

       Genomic instability caused by DNA damage

       Attrition of the protective chromosomal endcaps, the telomeres

       Alterations to the epigenome that controls which genes are turned on and off

       Loss of healthy protein maintenance, known as proteostasis

       Deregulated nutrient sensing caused by metabolic changes

       Mitochondrial dysfunction

       Accumulation of senescent zombielike cells that inflame healthy cells

       Exhaustion of stem cells

       Altered intercellular communication and the production of inflammatory molecules

      Researchers began to cautiously agree: address these hallmarks, and you can slow down aging. Slow down aging, and you can forestall disease. Forestall disease, and you can push back death.

      Take stem cells, which have the potential to develop into many other kinds of cells: if we can keep these undifferentiated cells from tiring out, they can continue to generate all the differentiated cells necessary to heal damaged tissues and battle all kinds of diseases.

      Meanwhile, we’re improving the rates of acceptance of bone marrow transplants, which are the most common form of stem cell therapy, and using stem cells for the treatment of arthritic joints, type 1 diabetes, loss of vision, and neurodegenerative diseases such as Alzheimer’s and Parkinson’s. These stem cell–based interventions are adding years to people’s lives.

      Or take senescent cells, which have reached the end of their ability to divide but refuse to die, continuing to spit out panic signals that inflame surrounding cells: if we can kill off senescent cells or keep them from accumulating in the first place, we can keep our tissues much healthier for longer.

      The same can be said for combating telomere loss, the decline in proteostasis, and all of the other hallmarks. Each can be addressed one by one, a little at a time, in ways that can help us extend human healthspans.

      Over the past quarter century, researchers have increasingly honed their efforts in on addressing each of these hallmarks. A broad consensus formed that this would be the best way to alleviate the pain and suffering of those who are aging.

      There is little doubt that the list of hallmarks, though incomplete, comprises the beginnings of a rather strong tactical manual for living longer and healthier lives. Interventions aimed at slowing any one of these hallmarks may add a few years of wellness to our lives. If we can address all of them, the reward could be vastly increased average lifespans.

      As for pushing way past the maximum limit? Addressing these hallmarks might not be enough.

      But the science is moving fast, faster now than ever before, thanks to the accumulation of many centuries of knowledge, robots that analyze tens of thousands of potential drugs each day, sequencing machines that read millions of genes a day, and computing power that processes trillions of bytes of data at speeds that were unimaginable just a decade ago. Theories on aging, which were slowly chipped away for decades, are now more easily testable and refutable.

      Although it is in its early days, a new shift in thinking is again under way. Once again we find ourselves in a period of chaos—still quite confident that the hallmarks are accurate indicators of aging and its myriad symptoms but unable to explain why the hallmarks occur in the first place.

      THE HALLMARKS OF AGING. Scientists have settled on eight or nine hallmarks of aging. Address one of these, and you can slow down aging. Address all of them, and you might not age.

      It is time for an answer to this very old question.

      Now, finding a universal explanation for anything—let alone something as complicated as aging—doesn’t happen overnight. Any theory that seeks to explain aging must not just stand up to scientific scrutiny but provide a rational explanation for every one of the pillars of aging. A universal hypothesis that seems to provide a reason for cellular senescence but not stem cell exhaustion would, for example, explain neither.

      Yet I believe that such an answer exists—a cause of aging that exists upstream of all the hallmarks. Yes, a singular reason why we age.

      Aging, quite simply, is a loss of information.

      You might recognize that loss of information was a big part of the ideas that Szilard and Medawar independently espoused, but it was wrong because it focused on a loss of genetic information.

      But there are two types of information in biology, and they are encoded entirely differently. The first type of information—the type my esteemed predecessors understood—is digital. Digital information, as you likely know, is based on a finite set of possible values—in this instance, not in base 2 or binary, coded as 0s and 1s, but the sort that is quaternary or base 4, coded as adenine, thymine, cytosine, and guanine, the nucleotides A, T, C, G of DNA.

      Because DNA is digital, it is a reliable way to store and copy information. Indeed, it can be copied again and again with tremendous accuracy, no different in principle from digital information stored in computer memory or on a DVD.

      DNA is also robust. When I first worked in a lab, I was shocked by how this “molecule of life” could survive for hours in boiling water and thrilled that it was recoverable from Neanderthal remains at least 40,000

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