Are you resigned to the “fact” that you must grow old, become frail and sickly, and probably die around the age of 80? What if aging is not inevitable nor irreversible? In this book, David Sinclair shares how aging occurs in humans and other life forms, and how it can be slowed, stopped, and even reversed—just like any disease. In this Lifespan summary, you’ll learn what scientists have discovered about aging, the solutions that are currently being explored, and how the future could look like with humans living longer and staying younger.
Lifespan: Overview
David Sinclair is a professor of molecular genetics at the Harvard Medical School and a leading researcher in the field of aging. After 30 years of research on human biology, he found that aging has a specific pathology. This means that it can be treated like other diseases. In fact, aging is the common factor behind all sorts of diseases—from cancer to heart disease, Alzheimer’s and osteoporosis—making it the mother of all diseases.
Today, human beings live longer but we’re plagued by physical impairment, frailty and ailments in old age. There’s no point increasing lifespan without healthspan. The goal should be to live longer while staying young and healthy.
Sinclair believes that in the foreseeable future, it’s possible for humans to live beyond 120 or even 150, without the frailty, diseases and disability we now associate with old age. If this sounds improbable to you, consider this–Cancer, gangrene and diabetes were once considered inevitable and irreversible, but can now be treated or cured. Aging can be seen in the same light.
Why We Age
To cure aging, we must first understand what it is and why it occurs. In the book, Lifespan, David Sinclair explains in detail:
• How the earliest life forms appeared and how they developed survival circuits which were then passed on to all other living creatures (including humans);
• How this survival circuit works in humans, including the longevity genes involved (sirtuins, mTOR and AMPK) and how they can be activated;
• The 2 types of biological information that allows us to function: digital information (DNA) and analog information (epigenome), what they do and how they’re different; and
• The 8-9 hallmarks of aging: These are what scientists now identify as universal signs of aging: genomic instability, telomere attrition, epigenetic changes, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, stem cell exhaustion, altered intercellular communication, and the build-up of zombie-like cells that inflame healthy cells. By addressing any of these hallmarks, you can slow down aging.
Sinclair explains the years of research and experiments done by him and his colleagues, and how the insights were combined into the first unified theory about aging: The Information Theory of Aging.
The Information Theory of Aging
This theory basically says that aging happens because of 1 definitive reason—the loss of epigenetic information over time. Here’s a simple graphical summary:
In our complete Lifespan summary bundle, we cover these biological concepts in more detail. Specifically, we’ll elaborate on survival circuits, longevity genes, DNA vs epigenomic data, and how they affect aging. These details are provided in downloadable and printable pdf/mp3 text, infographic, and audio summaries.
Pathways to Longevity and Vitality
What you need to know is that there are several pathways to activate the survival circuits that keep us young and healthy:
• Sirtuins repair our cells, change our DNA packaging and decide which genes to turn on/off. Mammals have 7 sirtuins: SIRT1 to SIRT7.
• Target of rapamycin (TOR) is a protein complex that regulates growth and metabolism. In mammals, this exists as mTOR. During good times, it drives cell growth. During bad times, it minimizes cell growth and recycles cellular components to conserve resources.
• AMP-activated protein kinase (AMPK) is a metabolic control enzyme that responds to low energy levels.
Sirtuins, TOR and AMPK are all activated by “good” biological stress, which triggers the body to conserves energy and repair itself (without permanent damage). This process is called hormesis.
What We’re Learning about Aging Solutions
Now that we know how aging works, we can learn to counter it. As of today, scientists have already uncovered several ways—including diet, exercise, and organic compounds—to activate or amplify our natural longevity mechanisms. However, more work is still needed to find the ideal solutions that work at a cellular or molecular level. Sinclair believes that once we find the ideal molecules for activating our natural defenses, aging will be even easier to prevent/cure than cancer.
Here’s a quick visual summary of the emerging solutions:
There are now countless studies to show the benefits of exercise and a good diet. Now, we also have evidence to show how these help to improve your lifespan and healthspan. Specifically, you can activate longevity pathways with “good” stress:
• Change how and what you eat, e.g. using calorie restriction, intermittent fasting, or replacing animal protein with plant protein; and
• Exercise regularly (including some high-intensity exercise) and exposing yourself to cold temperatures.
You can also use drugs/medicines to inject molecules that mimic the effect of stress inducers to inhibit mTOR, activate AMPK, or increase NAD levels. Examples include rapamycin, metformin, STACs (sirtuin-activating compounds) like fisetin, butein and resveratrol, and NAD boosters (e.g. NR and NMN) to activate all 7 sirtuins.
In our full 19-page Lifespan summary we’ll elaborate on:
• Each of the compounds mentioned above and their effects;
• Cutting-edge research and innovations that can slow/reverse aging or even help us to reset our entire epigenome in future–similar to restoring a scratched DVD. These include: Genetic therapy, drugs that can remove senescent or “zombie” cells, DNA sequencing and analytics, sensors and bio-tracking.
In short, we’re on the verge of fully understanding the mechanics of our biological clock and how to rewind it. In the future, we can potentially reset the epigenome and prevent aging.
Implications of Longevity
Sinclair is confident that Homo Sapiens will inevitably live longer—it’s a matter of when and by how much. So, it’s time to seriously look into the implications of this development.
Recognizing Aging as the Ultimate Disease
One of David Sinclair’s key messages is to stop fighting 1 disease at a time (which is both costly and ineffective), and to start recognizing aging as the ultimate disease that affects all other diseases. Aging does not directly cause death, but it increases our risks of getting sick/injured and dying from it. It’s like bringing someone to the edge of a cliff so they’re more likely to fall over.
Once aging is defined as a disease, it will attract more private and public investment, to significantly speed up the discovery of cures and preventive treatments.
Addressing the Implications of a Longer-Living Population
In a world where people live 30-50 years longer on average, but are still healthy and active, our lives will be very different. This has many ethical, social, political, and economic implications. Do get our complete Lifespan summary where we look deeper into questions like:
• Environmental damage and sustainability;
• Political, cultural and economic repercussions, e.g. changes to social security systems, how we view/define retirement, and other shifts in spending/saving patterns, healthcare needs etc.;
• Longevity’s impact on the rich-poor divide; and
• Opportunities for innovative solutions and new lifestyle possibilities.
Getting More from Lifespan
This is an extremely detailed book that explains what aging is, how it works, how it may be treated, and how new scientific discoveries could fundamentally change our future. David Sinclair presents complex biological concepts and scientific discoveries in terms that can be understood by the layperson. To get a more comprehensive understanding of healthspan and aging, as well as the range of aging solutions and implications outlined above, do check out the our full book summary bundle of Lifespan which includes a 19-page text summary, an infographic, and a 31-minute audio summary.
In the book, David Sinclair elaborates on each of the concepts above, including the hypotheses that were debunked and how scientists arrived at the current theories and solutions. He also includes details of lab experiments, vivid analogies, personal anecdotes, and illustrations to help the lay person understand complex biological concepts and jargon. Feel free to purchase the book here or visit https://lifespanbook.com for more details.
You may also wish to learn about about health and longevity in our Why We Sleep summary. Or, learn about the power of our ever-changing brain in The Brain that Changes Itself summary.
About the Author of Lifespan
David A. Sinclair (born 1969), the author of Lifespan: Why We Age – and Why We Don’t Have To, is an Australian biologist, inventor, author, and professor of genetics at Harvard Medical School. He is also the cofounder of the journal Aging, cofounder of the Academy for Health and Lifespan Research, and codirector of the Paul F. Glenn Center for the Biological Mechanisms of Aging. Sinclair holds a Bachelor of Science and a Ph.D. in Molecular Genetics, both from the University of New South Wales. He has published nearly 200 scientific papers, co-filed more than 50 patents, and cofounded numerous biotech companies. Sinclair has also received numerous awards for his research. In 2014, he was included in Time magazine’s list of the top 100 most influential people in the world. In 2018, he was made an officer of the Order of Australia for his research contributions.
Lifespan Quotes
“As a species, we are living much longer than ever. But not much better.”
“The important thing is not just what we eat but the way we eat.”
“If you’re interested in a long and healthy life, your diet probably needs to look a lot more like a rabbit’s lunch than a lion’s dinner.”
“Our genes didn’t evolve for a life of pampered comfort. A little stress to induce hormesis once in a while likely goes a long way.”
“Aging is a disease. And not only is it a disease, but it is the mother of all diseases, the one we all suffer from.”
“There is nothing more dangerous to us than age. Yet we have conceded its power over us.”
“[Aging is] the risk factor. Truly, by comparison, little else matters.”
“I have come to see aging as a disease—the most common disease—one that not only can but should be aggressively treated.”
“To understand the future, it is often helpful to travel into the past.”
