Lifespan
Lifespan: Why We Age – and Why We Don’t Have To by David Sinclair
🚀 The Book in 3 Sentences
Ageing is one of the biggest problems we are facing.
We should view ageing as a disease - it can then be cured.
There is no biological limit to how long we can live for.
🎨 Impressions
This book is one of the key readings in the longevity/ageing space. It was a full overview however a lot was unaccessible with a high degree of prior biological knowledge required to fully understand the details.
How I Discovered It
Longevity is a future growing area in the world. This book was recommended in the All In podcast as a good book covering the topic.
Who Should Read It?
If you are interested in a major future trend - the ability to reverse ageing and live longer. If you want to find ways to increase your lifespan and health span this book will inform you of the science and give you tips.
✍️ My Top 3 Quotes
Ageing, quite simply, is a loss of information.
As a species, we are living much longer than ever. But not much better. Not at all. Over the past century we have gained additional years, but not additional life—not life worth living anyway.
I believe that ageing is a disease. I believe it is treatable. I believe we can treat it within our lifetimes. And in doing so, I believe, everything we know about human health will be fundamentally changed.
📒 Summary + Notes
Changing How We Think About Ageing
One hundred and twenty years might be not an outlier but an expectation, so much so that we won’t even call it longevity; we will simply call it “life,” and we will look back with sadness on the time in our history in which it was not so.
There is no biological law that says we must age.
It takes radical thinking to even begin to approach what this will mean for our species. Nothing in our billions of years of evolution has prepared us for this, which is why it’s so easy, and even alluring, to believe that it simply cannot be done. But that’s what people thought about human flight, too—up until the moment someone did it. Then: liftoff. And nothing was ever the same again. We are at another point of historical inflection. What hitherto seemed magical will become real. It is a time in which humanity will redefine what is possible; a time of ending the inevitable.
As a species, we are living much longer than ever. But not much better. Over the past century we have gained additional years, but not additional life—not life worth living anyway.
We’re dying slowly and painfully. People in rich countries often spend a decade or more suffering through illness after illness at the ends of their lives. We think this is normal. As lifespans continue to increase in poorer nations, this will become the fate of billions of additional people. Our successes in extending life, the surgeon and doctor Atul Gawande has noted, have had the effect of “making mortality a medical experience.”
Why We Age (Biologically):
In this more nuanced view, ageing and the diseases that come with it are the result of multiple “hallmarks” of ageing:
Scientists have settled on eight or nine hallmarks of ageing. Address one of these, and you can slow down ageing. Address all of them, and you might not age.
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
We haven’t identified a singular gene that causes ageing. And we won’t. Because our genes did not evolve to cause ageing.
Longevity Genes
It’s worth pausing to consider how remarkable it is that we find essentially the same longevity genes in every organism on the planet: trees, yeast, worms, whales, and humans. All living creatures come from the same place in primordium that we do. When we look through a microscope, we’re all made of the same stuff.
We all share the survival circuit, a protective cellular network that helps us when times are tough. Yet different organisms age at very different rates. And sometimes, it appears, they do not age at all.
Every one of our cells has the same DNA, of course, so what differentiates a nerve cell from a skin cell is the epigenome, the collective term for the control systems and cellular structures that tell the cell which genes should be turned on and which should remain off. And this, far more than our genes, is what actually controls much of our lives.
Cells lose their identity and malfunction. Chaos ensues. The chaos materialises as ageing.
The Cost of Ageing
There are high health costs associated with treating diseases. From both an economic and emotional point of view, these are good investments. But consider this: though smoking increases the risk of getting cancer fivefold, being 50 years old increases your cancer risk a hundredfold. By the age of 70, it is a thousandfold. Such exponentially increasing odds also apply to heart disease. And diabetes. And dementia. The list goes on and on. Yet there is not a country in the world that has committed any significant resources to help its citizens combat aging. In a world in which we seem to agree on very little, the feeling that “it’s just the way it is".
Age is sometimes considered an underlying factor at the end of someone’s life, but doctors never cite it as an immediate reason for death.
The United States spends hundreds of billions of dollars each year fighting cardiovascular disease. But if we could stop all cardiovascular disease—every single case, all at once—we wouldn’t add many years to the average lifespan; the gain would be just 1.5 years. The same is true for cancer; stopping all forms of that scourge would give us just 2.1 more years of life on average, because all other causes of death still increase exponentially. We’re still ageing, after all.
Increasing Our Lifespans
Fasting, allowing our bodies to exist in a state of want, more often than most of us allow in our privileged world of plenty—is unquestionably good for our health and longevity. Just enough food to function in healthy ways and no more. It engages the survival circuit, telling longevity genes to do what they have been doing since primordial times: boost cellular defences, keep organisms alive during times of adversity, ward off disease and deterioration, minimise epigenetic change, and slow down ageing.
Completing vigorous exercise, exercise that feels challenging. Your breathing should be deep and rapid at 70 to 85 percent of your maximum heart rate. You should sweat and be unable to say more than a few words without pausing for breath. This is the hypoxic response, and it’s great for inducing just enough stress to activate your body’s defences against ageing without doing permanent harm.
Ethics of Ageing
The ethics of the technology become more difficult, though, if reprogramming becomes safe enough to use in a way that is preventive. At what age should it be given? Does a disease have to appear before an antibiotic activator of reprogramming is prescribed? If mainstream doctors refuse to help, will people head overseas? If the technology could significantly cut health care costs, should it be mandated? And if we can help children live longer, healthier lives, do we have a moral obligation to do so? If reprogramming technology can help a child repair an eye or recover from a spinal injury, should the genes be delivered before an accident happens so they are ready to be switched on at a moment’s notice, starting perhaps with an antibiotic drip in the ambulance?
The debate is not about whether this will happen; it is about what we should do when it happens
Understanding DNA
According to the Information Theory of Ageing, we become old and susceptible to diseases because our cells lose youthful information. DNA stores information digitally, a robust format, whereas the epigenome stores it in analog format, and is therefore prone to the introduction of epigenetic “noise.” An apt metaphor is a DVD player from the 1990s. The information is digital; the reader that moves around is analog. Ageing is similar to the accumulation of scratches on the disc so the information can no longer be read correctly. We need the polish.
Technology Extending Our Lifespan
In the near future, families will be monitored by biosensing wearables, small devices at home, and implants that will optimise our health and save lives by suggesting meals and detecting falls, infections, and diseases. When an anomaly is found, an AI-assisted, video conferenced doctor will send an ambulance, a nurse, or medicines to your door.
Let’s say, though, that all of these developments together will give us a decade. Once people begin to accept that ageing is not an inevitable part of life, will they take better care of themselves?
DNA monitoring will soon be alerting doctors to diseases long before they become acute. We will identify and begin to fight cancer years earlier. If you have an infection, it will be diagnosed within minutes. If your heartbeat is irregular, your car seat will let you know. A breath analyser will detect an immune disease beginning to develop. Keystrokes on the keyboard will signal early Parkinson’s disease or multiple sclerosis. Doctors will have far more information about their patients—and they will have access to it long before patients arrive at a clinic or hospital. Medical errors and misdiagnoses will be slashed. The result of any one of these innovations could be decades of prolonged healthy life.
The Economics of Ageing
There is simply no economic model for a world in which people live forty years or more past the time of traditional retirement. We literally have no data whatsoever on the work patterns, retirement arrangements, spending habits, health care needs, savings, and investments of large groups of people who live, quite healthily, well into their 100s.
Will people continue to work? What jobs will they be able to get in a world in which the labor market will already be being upended by automation? Will they spend a half century or more in retirement? Some economists believe that economic growth is slowed when a country ages, in part because people spend less in retirement. What will happen if people spend half of their very long lives out of work, spending only enough to get by?
Will they save more? Invest more? Get bored soon after retirement and start a new career? Take long sabbaticals from work, only to return decades later when their money runs out? Spend less on health care because they are so much healthier? Spend more on health care because they are living so much longer? Invest more years and money into their educations early on?
Rich/Poor divide consideration - That would be a world in which the rich and poor will be separated not simply by differing economic experiences but by the very ways in which human life is defined—a world in which the rich will be permitted to evolve and the poor are left behind.
The current education investments already produce tremendous dividends to our societies—for every dollar a government spends on education, that nation’s GDP grows on average by about $20.60. When we extend healthy lives, we exponentialise this investment. The longer people stay in the workforce, the better our return.
The Authors Longevity Routine:
I take 1 gram (1,000 mg) of NMN every morning, along with 1 gram of resveratrol (shaken into my homemade yogurt) and 1 gram of metformin.7
I take a daily dose of vitamin D, vitamin K2, and 83 mg of aspirin.
I strive to keep my sugar, bread, and pasta intake as low as possible. I gave up desserts at age 40, though I do steal tastes.
I try to skip one meal a day or at least make it really small. My busy schedule almost always means that I miss lunch most days of the week.
Every few months, a phlebotomist comes to my home to draw my blood, which I have analysed for dozens of biomarkers. When my levels of various markers are not optimal, I moderate them with food or exercise.
I try to take a lot of steps each day and walk upstairs, and I go to the gym most weekends with my son, Ben; we lift weights, jog a bit, and hang out in the sauna before dunking in an ice-cold pool.
I eat a lot of plants and try to avoid eating other mammals, even though they do taste good.
