Outlive: The Science and Art of Longevity, by Peter Attia and Bill Gifford (Harmony, 496 pp., $32)
We live in a golden age of health nuts, superfood gurus, exercise overachievers, and suspiciously young-looking longevity researchers. Yet for all this marketed youth, life expectancy is stagnant, scant progress has been made against the various dementias, and the average American keeps growing larger. Enter “geroscience,” the science of aging. In contrast with the generally poor popular discourse on the subject, physician Peter Attia’s new book, Outlive, written with journalist Bill Gifford, is a readable and wide-ranging primer to living a long life.
Attia first emerged from obscurity in 2011 as a charismatic advocate for ketogenic diets, later founding the Nutrition Science Initiative (NuSi) in 2012 with writer and journalist Gary Taubes (author of Good Calories, Bad Calories). NuSi was born of frustration with the general state of nutrition-science literature and, with $40 million from the John Arnold Foundation (which has a track record of funding metascience projects), promised to be the “Manhattan Project” of nutrition science. It ended up funding multiple diet studies, one of which tested the conventional wisdom about diets but could not confirm it; another that found inconclusive results; another that suggested that the conventional wisdom is wrong, at least with respect to fat accumulation in the liver; and another that, depending on one’s perspective, either confirmed or refuted conventional thinking.*
Now ten years older and wiser, Attia has spent the last half-decade building a medical practice and podcast that vacillates from longevity science to archery and racecars, just some of his many obsessions. Gone is the ketogenic-diet enthusiast; instead, he is candid about its disadvantages.
Attia starts the book by summing up what conventional medicine can treat well: “fast death,” broken bones, infections, damaged organs, and serious injuries. The astonishing rise in life expectancy over the twentieth century is attributable mostly to our near-rout of infectious diseases, especially in infancy and childhood. Medicine has made substantial progress against heart disease (still the leading killer of adults in the U.S.) and diabetes and scored some partial victories against cancer. These impressive results, unfortunately, are marred by what Attia calls the “Marginal Decade”—the drop in quality of life that most elderly people experience in their seventies and eighties. Focusing on aging itself, the most important risk factor for all these diseases, would seem like a logical next step.
Attia makes the case for focusing on aging as follows: centenarians experience a “compression of morbidity”—a smaller chunk of their life is spent infirm. That fact runs contrary to the popular notion that living longer would mean living as a modern Tithonus, gifted a long life without youth. Without randomized clinical trials showing that certain interventions will help people live longer, Attia relies on human studies on major age-related diseases; molecular and mechanistic studies from animal and human models; “Mendelian randomization,” a form of genetic epidemiology that, given certain assumptions, may be more reliable than others; studies of centenarians’ genetics (their lifestyles are amusingly unhealthy); and lifespan data from trials on animals separated by “a billion years of evolution.”
Attia is honest about the uncertainty of his patchwork approach, at least relative to the gold standard of randomized controlled trials. But on average, he thinks this strategy will tend to improve the reader’s prospects of living longer. If centenarians can achieve a longer and healthier life merely by delaying the onset of age-related diseases, what if ordinary mortals tried to reproduce their luck with novel tactics?
For diabetes and heart disease, the Attia approach is quite aggressive but not outside the medical mainstream. The American College of Cardiology offers a lifetime risk calculator for heart disease, and cardiac luminaries like Eugene Braunwald (founder of an academic research group, TIMI, that tested numerous important treatment in heart disease) have argued for proactive heart-disease prevention.
Attia concedes that his regimen is necessarily speculative when it comes to preventing cancer and neurodegenerative diseases. Most of his recommendations have limited downside—overly restful sleep or a trim physique—but his recommendation to pursue aggressive cancer screening is riskier. With the right combination of screening, and lucky developments in “liquid biopsy” technology, more cancer could be caught before it becomes metastatic, but many more individuals could be exposed to invasive biopsies or chemotherapy for slow-growing cancers that would never have killed them. For preventing Alzheimer’s disease and other dementias, Attia relies heavily on an approach pioneered by Richard Isaacson at Cornell that involves regular exercise, good sleep, reducing cardiovascular risk factors, and treating hearing loss. These are all good ideas, but their efficacy in preventing or delaying diseases is uncertain, as Attia himself acknowledges.
Attia’s book is filled with lucid analogies. Take the “Centenarian Decathlon,” a list of physical activities a healthy grandpa or grandma might want to carry out, such as picking up a toddler grandchild or carrying groceries for a few blocks. By calculating the physical demands of such tasks, as well as the predictable decline in fitness with age, farsighted 40-yearolds can guess at how fit they need to be to achieve those milestones in their eighties. Attia’s “first commandment of fitness: first do thyself no harm” emerges naturally from this perspective, given how crippling inactivity can be for older people.
Elsewhere in the book, Attia describes the discovery of rapamycin, a striking illustration of serendipity and persistence in drug research. The story starts with a scientific expedition to eerie Easter Island, filled with giant stone heads; then we meet biochemist Suren Seghal, whose characterization of the drug’s anti-fungal activity made him hopeful that he had discovered a cure for athlete’s foot. Later, Seghal persisted with experimentation even after his old company was bought up. Apart from its proven utility in transplantation, kidney cancer, and in drug-eluting-stents, rapamcyin holds a more elusive potential: life extension. Unlike other compounds with promising effects that later fail to replicate (most infamously resveratrol), rapamycin has generated effects that have shown up in multi-center trials of mice at various ages of treatment onset. Similar results have been found in yeast and fruit flies; the drug is now being tested in companion dogs.
It’s hard to argue with more exercise, strict control of risk factors, and better sleep, but from a population-level perspective, the biggest challenge is adherence. What percentage of people will consistently carry out such changes? Some insight may be gained by looking at what percentage of Medicare patients who have recently suffered a heart attack actually take high-dose statins, as nearly all should. The answer is no more than 35 percent, and some argue that the number is substantially lower. And still-lower numbers would likely follow government guidelines for calorie consumption or activity levels, let alone the more stringent standards Attia expects. The focus, then, should be on developing drugs that can slow aging, not a suite of lifestyle interventions that, however effective, will never be adopted en masse.
Policymakers should take heed. From Italy to America, longer life expectancies without corresponding improvements in “healthspan”—the years one spends in the prime of one’s health—are challenging developed-world safety nets. Yet the National Institute of Aging (NIA) budget is small. In 2023, the operating plan for the NIH apportions about $4.4 billion to the NIA, while the National Cancer Institute alone receives about $7.3 billion. Yet many more people will grow old than will ever develop cancer. If, as geroscientists hope, directly treating aging (instead of age-related diseases) improves health span, then longevity science may help resolve this elder-care budget crisis.
Apart from more research into the basic biology of aging, some specific “mega-projects” in aging could easily absorb considerably more funding. For instance, the Interventions Testing Program (ITP), which rigorously tests various compounds on laboratory mice in three separate laboratories, has identified several that reliably extend mouse lifespan. Some, like rapamycin, acarbose, and canagliflozin, are already FDA-approved for humans, though for other conditions. Funding in-human studies for both aging and age-related diseases—as, for instance, some have already proposed for rapamycin and Alzheimer’s disease—and for promising off-patent drugs should be an NIA priority, especially since these generic drugs are unlikely to see substantial future investment from industry. Expanding the ITP’s capabilities by increasing the number of compounds and testing in combinations would be a natural complement to this effort. Another possibility would be adding exotic interventions such as partial reprogramming (which aims to restore youthful patterns of gene expression) to the ITP, which currently prioritizes interventions that can be delivered through diet.
I’m a minor exercise fanatic, though I can’t swim a 21-mile channel like Attia. I’m even a closet diet experimenter and an occasional blood-glucose tester. So I’m naturally drawn to Outlive’s prescriptions, and I even believe that my habits will net me a few extra years. But I’m also eagerly awaiting some distant cousin of rapamycin, acarbose, or a yet-unknown therapeutic, perhaps a decade or two hence, winning FDA approval for anti-aging. I hope they come up with a good name. My vote goes for Ambrosia.
