Lifespan: Why We Age — Book Summary

Lifespan: Why We Age Book Cover

Lifespan: Why We Age ― and Why We Don't Have To

by David A. Sinclair

Published: 2019 | 416 pages
Rating Amazon:  stars rating 4.5 
Rating by reviewer:  stars rating 4.3 
Author of the article: Abdul Saboor Khaliq
Date of the summary: Jul 6, 2020

To cure aging, the things we do go deep inside our cells and affect the genome and epigenome. Learn the things we can do to promote health and longevity.

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Lifespan: Why We Age Book Cover

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In this book "Life span - Why we age? And why we don't have to?" the writer David A. Sinclair describes aging and its pathophysiology in perfect harmony. Going through the book feels like a smooth and steady ride. In the beginning, the writer explains the working of the little genome the most ancient organisms on this planet Earth possessed. He then describes how this genome is expressed today in organisms as simple as yeast to organisms as complicated as human beings. He then explains the effect of various lifestyles on this cellular network and genes and how this forms the basis for treating aging. To the writer, aging is just a curable disease. According to the writer we need to consider every aspect of our lives to promote longevity. And we can only succeed in curing aging and living peacefully as a result of a collective effort by all of us. It is not a day's task.

Interesting quotes from the book

It takes courage to consciously think about your loved ones’ mortality before it actually happens. It takes even more courage to deeply ponder your own.

— David A. Sinclair, Lifespan: Why We Age

Because as it turns out, exposing your body to less-than-comfortable temperatures is another very effective way to turn on your longevity genes.

— David A. Sinclair, Lifespan: Why We Age

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.

— David A. Sinclair, Lifespan: Why We Age

Summary of the book Lifespan: Why We Age

Human beings, being the curious and inquisitive beings, have always strived to make their lives better physically, mentally, socially, financially, and economically. When it comes to improving the quality of life, health, disease, disability, and aging are the few things that come first and foremost in our minds. Human beings are always very cautious about staying young with advancing age and delaying aging in general. Let's go billions of years back to understand what made our ancestors so strong and powerful in the harsh environment of the planet Earth to understand what it takes to stay young in the face of the trialing environment.

The earliest organisms on the planet Earth used to inhabit the water bodies, the most benign of all. They faced the volcanic eruptions, trilling heat, intense piercing radiations, and toxic gases and under-went wear and tear with time. The writer has used the Latin term, Magna Supersites, for these ancient organisms. Only the best of these ancient organisms survived. These organisms adapted themselves to the harsh environment of the Earth. Hundreds of studies of these simple organisms demonstrated that they keep their face up to the harsh environment by the possession of two genes. Let's say that they were Gene A and Gene B. Gene A halted reproduction in times of distress while Gene B silenced Gene A in times of favor so that these tiny organisms could reproduce. Over time, Gene B developed another function of repairing DNA.

Don't worry if you have never pondered on things like death and aging. Even the discoverers who devoted their lives to making enormous discoveries never really bothered to think about the things causing things as disastrous as death and aging. And at last, when they thought about the causes, they narrowed them to nine significant ones. These "hallmarks" of aging are:

  • DNA damage leading to genomic instability.
  • Attrition of the protective chromosomal endcaps, the telomeres.
  • Alterations to the epigenome that controls gene turn on and off.
  • Loss of healthy protein maintenance, known as proteostasis.
  • Deregulated nutrient sensing.
  • Mitochondrial dysfunction.
  • Accumulation of senescent zombielike cells that in?ame healthy cells.
  • Exhaustion of stem cells.
  • Altered intercellular communication and the production of in?ammatory molecules.

These nine hallmarks are of significant importance. We should ponder on these points. If we work on some of these points, we will do wonders. And addressing all of these might even stop aging. But the writer thinks that we should simplify our understanding. The writer considers one single cause of aging to be a gradual loss of information. Human beings store information in two ways. One is digital, and the other is analog. A genome is a form of digital information. It has a unique sequence of nucleotides, and specific pairing of the four nitrogenous bases adenine, cytosine, guanine, and thymine. Chromatin is a form of Analog. It is famous by the name of the epigenome these days.

The writer has done a lot of experiments on yeast and is a great admirer of this simple organism. Through his work, he has cleared our misconceptions. He has told that:

Human-genome discovery is by no means exhaustive.

A gene can comprise as little as 21 base pairs.

The histones and other nuclear proteins forming chromatin and chromosomes have an impact on controlling the gene expression.

If the genes are piano, the epigenome is the pianist.

Just like the great survivors of the remote past, human beings also possess 'vitality genes' or 'longevity genes.' These genes go by the name of 'sirtuins' named after the yeast SIR2 gene, the first one discovered. There are seven sirtuins in mammals, SIRT1 to SIRT7. Two other longevity genes are Rapamyocin or TOR and AMPK. SIRT1, SIRT6, and SIRT7 control the epigenome, and DNA repair. SIRT3, SIRT4, SIRT5 live in mitochondria and control metabolism.

The writer tells us that division and fertility are indicators of healthy and nourishing yeast. Through his experiments, he proved that yeast has a 'mating-type information gene' (descendent of gene A) and a SIRT2 (descendent of gene B), which keeps the 'mating-type information gene' off. The unstable, circular, and damaging rDNA piles up in cells of yeast and kills them. In response to the accumulation of this toxic rDNA in the cell, SIRT2 moves away from silencing mating genes into the task of stabilizing the unstable genome. Both male and female genes turn on, and this leads to infertility, the very indicator of aging in yeast.

Sirtuins in the yeast control fertility. In humans, they have other roles as well. One of them is removing acetyl from histones and proteins that regulate cell division, DNA repair, and inflammation. The vitality genes also have a role in hormesis.

Many scientific theories suggest that the loss of information causes aging. The writer has narrated an experiment conducted on mice. A DNA cutting gene from slime mold when injected into the mouse's embryo cut the DNA of the mouse at specific places. The ICE mouse formed from this defected embryo underwent early aging.

Now that we have established the role of genome, epigenome, hormesis, and various enzymes in aging, it is time to dwell on the ways to combat aging. Aging is nothing more than a disease. And it is a terrible disease. It gives you skin-wrinkles, gray hair, aching joints, hip fractures, delayed healing of wounds, diabetic feet, myriad of cancers, and what not?

When it comes to improving lifestyle to treat aging, the first thing that crosses our minds is diet. And the writer's advice is to eat less. The calorie restriction is even more important than eating the right food . The best way is intermittent fasting with periodic intervals of calorie restriction.

When it comes to the type of diet, the well-known fact that animal-based products do worse holds right. The plant-based products do good. Among proteins, carbohydrates, and lipids, proteins are the healthiest. And all of us know that proteins consist of amino acids. An essential thing for our bodies is the "essential" amino acids, as the name shows. There are nine essential amino acids. We can't live without methionine, and it is present mainly in animal products but, the fact is the amount obtained from plants is just enough. In smaller amounts, Methionine, Arginine, and branched-chain amino acids (leucine, isoleucine, and valine) activate mTOR and do good. Leucine is also essential for the body, and it boosts muscles. But in large quantities, it activates mTOR for long periods and leads to aging. And this holds for all the amino acids out there. And this is why vegetarians eating just the right amount of proteins are at the benefit as compared to people who eat meat.

The second thing which comes in our minds related to lifestyle is exercise. It is a fact that exercise improves the blood flow and health of our heart, lungs, and muscles. It is also associated with delayed erosion of telomeres in all cell types, thus causing a long and healthy life. Exercises induce vitality genes. And the good news is that you don't even have to spend hours exercising to prevent aging. Half an hour a day is enough. However, the intensity of exercise matters and the intense exercises do good to your body.

A cold temperature is just a form of stress and it is good for our health. Our cellular stresses activate AMPK, turn down MTOR, induce sirtuins, and augment NAD levels. But stresses like smoking destabilize the epigenome and this promotes aging Exposure to azo dyes, such as aniline yellow, and organohalides present in solvents, degreasers, and pesticides also cause DNA damage.

The bottom line is that the minor stresses, cold stress, low-calorie diet, exercise, and the low amino acid diet activate the three main vitality pathways-mTOR, AMPK, and sirtuins. Moreover, drugs like rapamycin, metformin, and resveratrol augment the vitality pathways thereby promoting health.

Science and technology are there to make advancements and facilitate human beings. Advancement in science and technology is the development of senolytics to kill the senescent cells because these cells only produce pro-inflammatory substances that do havocs. And the way we are progressing it seems so that we will have bio-sensible wearables and small home devices to monitor and optimize health. It is a fact that most cancers arise through mutations in the genome. The advancements in the future will help to map out every single person's genome to know the mutation beforehand. This early diagnosis of all the lethal and debilitating diseases like Parkinson's, multiple sclerosis, etc.

To live a healthy life, we also need to have a good environment. Unfortunately, our earth is only getting warmer and more polluted with every passing day. To live longer and healthier, we also need to reduce the ongoing global warming.

Delaying aging and preventing deaths might put you into thinking that this may lead to humans and humans everywhere and the planet Earth might explode. But the truth is saving deaths only add annually fifty million people. And fifty million might seem like a lot, but it is only a speck as compared to the birth rate. What we need is to control the annual birth rate.

So, putting a full stop to aging is a multifactorial yet possible thing. We should start doing what we can to live a long and healthy life.

We should always keep in mind that curing aging is going to take decades. If all of us start working towards it efficiently, we will be able to see results in decades. It is not one person's job. Nor can it be achieved in a day. Moreover, curing aging will affect our lives and this planet we call home, socially and economically. We need to develop policies beyond our own lives to create peace in this home of ours. We need to spread awareness in the public and the governments need to develop policies beyond their tenure to achieve a haven.

What can we learn from the book Lifespan

Lesson 1: Improve quality of life

Improving the quality of life is more important than merely prolonging life.

Lesson 2: Slow down aging

Aging is a curable disease.

Lesson 3: Understand pathogenesis of aging

Everything that we do (from running to exercising, and eating - from red meat to spinach) influence us deeply on the cellular level by affecting the metabolic pathways, and this form the pathogenesis of aging.

Lesson 4: Collective effort

To improve the quality of life, we need to make a collective effort. It is not one person's job.

Review of the book Lifespan: Why We Age

The writer has written this book very beautifully in perfect harmony. Reading this book is like riding the car on a smooth road. The writer has explained all the phenomena by using perfect metaphors. The boo is understandable by the laymen. However, while using metaphors, the writer tends to drift apart from the main topic. The writer has explained the factors that can improve the quality of life and how this can affect us socially and economically.


Reading this book was a fruitful activity. It was a day well spent. I would recommend this book. This book perfectly explains the things we should be doing in our monotonous and melancholic lives to spend a healthy life. If we spend our lives according to this book, age will become just a number to us. The good part about this book is how the writer talks about very serious things like how the increment in the average age of man can affect us socially and economically, what we should be doing to live a good life as a family on our home, i-e; Earth, the collective benefit of mankind should always be preferred over the individual benefit.

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