Lifespan by David Sinclair and Matthew LaPlante Analysis and Summary

Why We Age and Why We Don’t Have To

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What Is the Book About?

Lifespan is David A. Sinclair’s first novel which challenges the seemingly undeniable truth that aging is inevitable. As an acclaimed researcher at Harvard Medical School and one of TIME’s most influential people, David’s book will provide you with a current status that we’re at with understanding lifespan and health-span in humans. So whilst the book is called Lifespan, it could quite easily have also been called Health-span since it discusses in much detail the science behind living longer, but in a disease-free state. Importantly, the societal impacts that coincide with an aging population is also discussed. 

“Aging is a disease, and that disease is treatable.”

~ David Sinclair

About the Authors

David Sinclair, Ph.D., AO, is a professor of genetics at Harvard Medical School. One of the leading innovators of his generation, he has been named by Time as “one of the 100 most influential people in the world” and the top fifty most influential people in healthcare.

He is a board member of the American Federation for Aging Research and has received more than thirty-five awards for his research and major scientific breakthroughs.

Matthew LaPlante is an associate professor of journalistic writing at Utah State University, where he teaches news reporting and feature-writing. A former US Navy intelligence specialist and Middle East war correspondent, he is the author of Superlative: The Biology of Extremes and the co-writer of multiple other books on the intersection of science and society.

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Summary of Lifespan by David Sinclair

Why We Age; Informational Theory of Aging 

Aging is a complex, multi-factorial process that so far is best described through different “hallmarks of aging”. These hallmarks include stem cell loss and genetic instability. Whilst the hallmarks of aging are a useful framework for focusing on individual areas for research, there is also much overlap amongst them. Instead, David provides his own theory for aging that unifies the hallmarks by being upstream of them. David’s theory is that aging is quite simply a loss of information. This ‘information theory of aging’ builds upon the Mathematical Theory of Communication by Claude Shannon. To understand the basics of the Mathematical Theory of Communication you need to understand that there are two ways of transmitting information; digital and analog. The main difference between them is that analog information is continuous whilst digital is discrete. The problem with analog information, however, is that it can get disrupted by noise. 

We have both analog and digital information within each of our cells; the digital information being our genetic code with our analog information being the epigenetic code that determines and dictates which genes are expressed in the cell. Based upon the Claude Shannon’s work we know that it’s analog information that is prone to the accumulation of noise and disruption over time. Therefore, David suggests that noise accumulation in epigenetic information disrupts gene expression and other nuclear processes within a cell leading to malfunctioning and inevitably aging of the organism. 

To use another analogy from the book it’s like a DVD whereby the digital information is recorded on the DVD whilst the analog information is on the surface. The DVD surface could get scratched. That scratching of the surface, this analog information, can disrupt the reading of the digital information encoded on the DVD. 

Why We Don’t Have To Age?

Now that you understand what aging is, it is now time to discuss if it is possible to prevent or even to reverse this aging process? 

To summarise a large chunk of the book, David suggests that there are three main actions you can take if you want to try and prevent or slow down the aging process.

1. Eat less
2. Exercise more
3. Go out of the thermal-neutral zone

Eat Less

The first action is to eat less. This is otherwise referred to as calorie restriction – reducing your daily intake without causing malnutrition.

The idea behind calorie restriction to prevent aging is that the amount of damage induced within the cell is reduced in addition to the activation of processes that can help to reverse the damage that’s accumulated. However, eating less may not be the easiest strategy to follow. Instead, much research is being focused molecules that can mimic this restriction process.

The Nutrient Signalling Pathways – “Good Stress”

Activation of repair processes in a cell is tightly associated with nutrient signalling pathways. The nutrient signalling pathways feature many proteins often referred to as longevity regulators. This is because, in animal models where the genes encoding these proteins have been either deleted or enhanced, lifespan extension has been observed. 

Alternatively to gene editing, these proteins can be inhibited or activated through the use of different molecules that by targeting these proteins within the nutrient signalling pathways modulate the signalling flux and can promote the “good stress” in the cell. The different molecules discussed in the book included rapamycin, metformin, resveratrol and NAD⁺ precursors. The idea is that you want to be able to promote the stress resistance signalling and to prevent excessive growth signalling that causes more damage. This is thought to mimic calorie restriction.

One molecule discussed in great depth is metformin which you may already be taking because it’s a type 2 diabetes drug. But now metformin is being tested to see if it can treat aging itself. This is being done through the Targeting Aging with MEtformin (TAME) trial that recently started and is trying to examine if metformin can delay the onset of age-related diseases. The problem is that whilst this is a really good step forward, aging currently isn’t recognized as a disease, so if there is a link between metformin and preventing aging you’d have to be prescribed the drug so you’d likely have diabetes melitus.

Nevertheless, you may have access to some of the other molecules discussed. The second one being resveratrol. Resveratrol is thought to prevent the aging process by activating sirtuins and resveratrol can be found in amongst things, grapes, and in red wine. But, to get the same dose of resveratrol as has been used in experimental studies you would have to drink a lot and a lot of wine. 

The last set of molecules that from experimental studies seem to slow the aging process are NAD⁺ precursors, one of which is NMN, otherwise known as nicotinamide mononucleotide. The idea behind NAD⁺ precursors is to enhance the levels of NAD⁺ that have been shown to decline as we age. Interestingly, sirtuins require NAD⁺ to function which further strengthens the support for NAD⁺ supplements. You can buy NAD⁺ precursors from different companies and so people are taking them, including David himself and his friends and family. In particular, David’s Dad has noticed several benefits from taking NMN. However, some of the sources of NAD⁺ precursors can be quite costly and considering they have yet to be scientifically proven to have an impact in humans with regards to slowing the aging process, it may be wise to wait a while longer as research continues. Like resveratrol, NMN can also come from your diet; it’s found in broccoli, cucumber, avocado, tomatoes and edamame, however, as with resveratrol you need to eat a lot and a lot of broccoli to get the dose of NMN that matches what you can take with supplements. 

What Does David Do?

David’s regime;

• 1 gram of NMN
• 1 gram of resveratrol 
• 1 gram of metformin
• Takes a daily dose of vitamin D, vitamin K₂ and 83 mg of aspirin
• Given up desserts
• Tries to skip a meal per day
• Eats a generally plant-based diet
• Walks a lot including upstairs and will go to the gym with his son

Disclaimer; David is not a medical doctor, he is a researcher. Whilst he is happy to share his regime he reinforces three key disclaimers;

1. What he does isn’t necessarily nor even likely what you should do
2. David does not know if what he does will work for him
3. There are no treatments for aging that have been through rigorous long-term testing

Exercise More

The second way to prevent aging is to exercise more. The benefits of exercise are thought to act through activating these stress resistance pathways within a cell-like with caloric restriction, but many studies have also shown that exercise can help prevent telomere decline.

Go Outside the Thermal-Neutral Zone

Most of our lives are spent in heated rooms. So, temperatures above and below what our bodies are comfortable with. It’s not entirely clear how going for a walk in the cold can help prevent the aging process yet, but again it’s thought to activate these stress-resistant pathways. So consider taking saunas, working at your desk in a T-shirt, or turn down your radiators. 

How to Recover the Lost Information During Aging?

We’ve come a long way in understanding the aging process but there are still some key aspects to the aging process that we are yet to fully understand. To understand what these components are, we can go back to Claude Shannon’s Mathematical Theory of Communication. In Shannon’s theory, three components are required to recover lost information due to the accumulation of noise in analog signaling;

• an “observer” that recognizes the original signal before noise
• storage of the “correction data” required to revert the current signal to the original 
• a “correction device” that performs the reversal and removes the noise from the signal to get you back the original signal.

David likes to think that there could be similar biological components that can do this same thing, but with noise accumulation in epigenetic signalling to prevent aging. With this additional understanding it may become possible to reverse the aging process by activating these “correction devices” to recover the information that was lost. Whether this is even possible it is not currently known but if it is, is their just one or several biological components involved in each of these aspects? This is exciting but it may be a while until any therapeutics come into fruition. 

Technological Advances

In addition to the advances made in science of aging there has been many

technological advances such as biometric tracking or bio tracking. This is similar to the concept of virtual medical assistants that Eric Topol discusses in his most recent book ‘Deep Medicine’. In a similar way to bio tracking, virtual medical assistants are devices that can track a wide variety of biometrics, many of could be linked with your phone and could inform you on such metrics like how much you slept, how the composition of your blood is doing, what foods you should be taking, for example. It definitely seems to be the way that technology is going and could enable early indications of several diseases so that they can get treated before getting too severe. There’s a lot of information you can even get from just phone usage; how fast you type, what you are typing, what apps you are using. What all this bio tracking technology really reminds me of

is a quote from Yuval Noah Harari’s book ‘Homo Deus’ which is that “the 20th-century medicine was all about healing the sick but now it’s about upgrading the healthy”. 

Societal Issues; A Much Needed Conversation

“Upgrading the healthy” is not necessarily a bad thing; the concern regarding aging research is that those who get this additional health are also the ones that have the wealth to afford the health. David correctly asks this question in this book; “How will we extend human healthspan with equity, equality and human decency?”. Unless aging is recognized as a disease, once we know that some of these supplements actually do have an effect preventing aging, the supplements will only be available for those who can afford them because they won’t just be prescribed them. And so what may happen is that those who have the wealth to afford these supplements, they get better health and they now have more time to make more wealth. With more wealth, they could afford even more supplements to further optimize their health becoming a perpetual cycle. The open question is how can we avoid this from happening? 

The second concern regarding life extension is overpopulation. David addresses this by suggesting that instead of overpopulation it’s more about our over-consumption. So the message isn’t all doom and gloom but the point is we need to be having these conversations now before it is too late.

The Future?

Last year that the World Health Organisation recognized old age in the International classification of diseases. If aging gets FDA approval there would be many changes regarding both aging research and who has access to treatments that can prevent aging. Without supplements though, by eating less, exercising more and being in the cold every so often, anyone has the potential to extend their lifespan to some extent. 

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