Immortality vs Aging Later

For all our high-tech cities, complex financial products, and cutting edge medicine, humans have not managed to push back very much against the one certainty that awaits all of us - death. Though we live longer now than we did in the 1950s, much of this increase can be attributed to significant improvements in infant and youth mortality. In the 1950s, average life expectancy for the Western world hovered around 65-70 years of age, which included a 25% infant mortality rate (dying before the age of 5) and a 16% youth mortality rate (dying before the age of 15). Today, life expectancy in the United States has risen to ~78 years of age, which undoubtedly reflects an infant and youth mortality rate that has been brought under control.

Despite enormous advances in keeping young children alive, extending human lifespan over the past century, give or take a decade, has not made much progress. This lack of progress is not for lack of trying. Though we’ve known that cells experience senescence - programmed aging - since the 1960s and that the accumulation of senescent cells eventually leads to dysfunction, disease, and death, there has been little progress made in addressing inevitable, age-related breakdowns. In fact, in many ways, it can seem that we are moving in the wrong direction. 

Currently, life expectancy in the United States is stagnant. After almost a half-century of steady increases, the needle has not budged for the last five years. Much of this can be attributed to increased drug overdoses, both on Native Reservations and across America. On the reservation, marginalized groups like American Indian and Alaskan Natives have seen a massive increase in age-adjusted mortality. Two decades after we started counting, they are experiencing 146 more deaths per 100,000.

Though native populations have been affected disproportionately, the rate at which those between 25-44 are dying from drug overdoses is alarming and has contributed significantly to the shift in life expectancy. In addition, another strange trend has emerged in those between the ages of 55-64. Though this older population experienced a brief downturn in deaths from chronic respiratory disease and heart disease for the first half of the new millennium, this group has seen a steady increase in all causes of death, except assault and transport accidents.

These data suggest that death is coming for Americans sooner than in previous generations, and decreases in infant mortality can no longer hide the inescapable trend. Rather than continuing to increase our life expectancy, we are seeing old age and stagnation overtake the population - making the dream of a longer, healthier life seem more like a mirage in the distance. 

With these depressing statistics in mind, there is perhaps no better time for Dr. Nir Barzilai to have released his first book - Age Later: Health Span, Life Span, and the New Science of Longevity. 

How to Age Later

First, a little bit of context of why it’s worth paying attention to what Dr. Barzilai has to say about Aging, despite the grim outlook the data suggest. This is a man who has dedicated his career to untangling the mysteries of aging, specifically by examining those who maintain health and vigor into the later years of their long lives - people he terms “SuperAgers.” He is the founding member of the Institute for Aging Research, the Scientific Director of the American Federation for Aging Research, and is the founder of CohBar, a biotech company working on mitochondria-based treatments for age-related diseases. He is also the Chief Medical Advisor of Life Biosciences, the first publicly traded biotech to focus exclusively on questions of longevity. His model system, spry centenarians, has had many successes.

 Back in the late 1990s, Dr. Barzilai recruited a small cohort of extremely healthy people to the Longevity Genes Project at Albert Einstein College of Medicine in the Bronx. The majority of these volunteers were Ashkenazi Jews who came from families where members had reached the age of “seventy [and] have twenty to thirty more mostly disease-free years ahead of them.” Centenarians were well known by this point, with long-living blue zones distributed across the world in places like Japan, Iceland, and Ecuador. Barzilai’s study, however, was the first one to systematically ask the question - how is it that “most people are ill for an average of five to eight years prior to death, while centenarians tend to maintain most of their abilities and are ill for only about five to eight months before their deaths?”

The answers came slowly, but the project has paid dividends. The first half of the book covers the three major findings that have come out of it - that a certain kind of cholesterol seems to be protective against the wear and tear of aging, that growth hormone plays a central role, and that mitochondria - long thought of as powerhouses and little else - might play an instrumental role in longevity.

The first set of findings about cholesterol were originally published in 2003, and represent the discovery of the first “longevity gene” to come out of the project. Using anecdotes and real-life examples, Dr. Barzilai explains how the genetic relatedness of his experimental cohort (all Ashkenazi are thought to descend from a group of four women) helped his team identify relevant signals among the genetic noise that is prevalent in any population. For many scientists, this finding would have been enough to make a career out of, but Barzilai freely admits his goal is technological development - not pure scientific understanding. After the cholesterol victory, he shifted his attention to the interesting relationship between size and longevity. Though large animals like elephants have longer lifespans than small animals like mice, the relationship within a given species is the reverse. It has been shown that “Small dogs live longer than big dogs, ponies live longer than horses, and mice born with a genetic defect that causes dwarfism live substantially longer than mice without this defect.” 

When the researchers pursued this correlation in their centenarians, they found that it held in humans, too. In the chapter on growth hormone, Barzilai manages to simplify the complex network of interactions sufficiently that the reader is made aware of the complex system being interrogated, without being lost in the details.

Again and again, Barzilai manages to hit this sweet spot. Many of the chapters contain technical information about proteins and pathways, a reflection of the bullet-target methods often used by genetics researchers that are looking to find the underlying cause of a phenomenon. But each chapter takes a moment to orient the reader, forgiving you for not having an immediate familiarity with DNA methylation, histones, inflammation, growth hormone, or other technical terms used in the book. 

While the first half of the book focuses on bringing the reader up to speed on the developments that have come out of the Longevity Genes Project, the second half is all about the technical applications that are being developed, and the hope that this kind of research brings to all of us. Both at Albert Einstein College of Medicine, Barzilai’s home institution, and at CohBar, the biotech company he founded to develop and bring to market treatments, advances are being made that Barzilai is certain will help the next generation Age Later. 

For those more interested in actionable advice than in the scientific details alone, fear not. The last 100 or so pages of the book he goes through the most promising biochemical discoveries that he and his team have made - from the off-label effects of the diabetes medication Metformin to the discovery of “humanin,” an anti-aging peptide produced by the mitochondria that, due to some patent strangeness, has fallen through the cracks of drug delivery. 

The penultimate chapter, “Stop the Clock,” contains the most actionable advice in the book. Barzilai acknowledges that there is a strong genetic component to longevity that many of us do not have - but takes some sixty pages to explain the ways that lifestyle, mindset, and some light supplementation can help those of us that aren’t genetically predisposed to longevity get on the right track. 

Overall, the book is a succinct overview of the state of aging research. It’s a beautiful platform for showcasing Barzilai’s dedication to understanding how to extend lifespan, and a reflection of the kind of positive relationships it’s possible for a researcher to have with their subjects. Because of the unusual model system, actual humans, there are rich stories of personal history scattered through the sometimes technical text. The textures of the Bronx come through in the stories of Irving Kahn, who kept working until the year before his death at the ripe age of 109, of Freida and her son Jerry, father-in-law to Dr. Barzilai and strong personal motivation for the research. And of Uncle Ervin, survivor of six holocaust camps, who illustrates the principle of hormesis - how a little bit of a bad thing can actually be good for you.

Overall, Age Later: Health Span, Life Span, and the New Science of Longevity offers some much-needed perspective on what it means to live a good life, and the ways that it’s possible to achieve it. Though many of the findings appear to be dependent on the role of fortune and family, the second half of the book explains all the ways in which we can push against fate by changing our practices. One of the main things I took away from it was that aging, like most topics that touch so many different corners of our biology, is complex. 

In the closing paragraph, Barzilai leaves on an optimistic note. He reminds us that “the ability to reverse aging is already contained within the human body. If we take the sperm of a seventy-year-old man and the egg of a fifty-year-old woman, we can determine the age of the sperm and the egg, and those ages will be about the same chronological ages of the donors. But we know that if you fertilize the fifty-year-old egg with the seventy-year-old sperm, the new cells that divide and begin the life of the fetus start at age zero.” It turns out that the great minds of our generation are already hard at work figuring out how to make that work for us.

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