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20200223 – Lifespan Why we age

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MAIN IDEA:

The main idea of this book is that aging and deterioration of human abilities with age is not an inevitable natural process caused by irreversible accumulation of errors in DNA, but rather disease caused by accumulation of epigenetic changes that regulate genes expression. As such, this disease could be treated by restoring epigenetic environment of youth that would allow normal DNA expression and elimination not only of old age disabilities, but even death itself. In support of this idea author discusses results of his team research and findings.

DETAILS:

Introduction: A Grandmother’s Prayer

Author starts this with description of his grandmother’s quite adventurous life and her vitality that disappear with age, substituted by physical and then mental disabilities. This was one of important stimuli for author to go into the specific field of biology and medicine.

Part 1: What We Know (The Past)

Chapter 1. ‘Viva Primordium’

This starts with description of initial evolutionary development and how living things developed ability to fix breakdowns of DNA. Here is pictorial presentation:

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From here author moves to discuss overall approach to healing, noting that it is often fight against symptoms, rather than real causes. He discusses cancer as generic disease of immune system, rather then specific illness of lung or liver or some other part of the body. Author also discusses aging in evolutionary terms as seen via group selection, which prevents selection for immortality or even especially long lifespan. Author summarizes current prevailing attitude that aging is result of combination of factors and provides the list of these factors:

  • 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 

Author does not really reject any of this, but rather goes around, first stating that he understands low feasibility of one cause for complex processes, but then presenting just such cause at the high level. He views bodily functions based on two types of information processing: digital presented by DNA and analog presented by epigenetics, with former reliable and unchangeable and latter vulnerable and is often broken due to variety of contingencies. Author correspondingly believes that this analog process is more or less regularly cleaned up and presents genes named SIRT1 to SIRT7, and a few other genes and enzymes that do just that. The final point author makes that accumulation of too many problems over time at epigenetic level makes this cleansing and fixing process less and less effective leading to aging. Consequently medical intervention that would restore effectiveness of such process would lead to elimination of aging.

Chapter 2. The Demented Pianist

Here author discusses incompleteness of DNA mapping and what he calls the Information Theory of Aging that he formulated. It started with research on one of the simplest living creatures – yeast. Author used it to analyze protein SIR2. Here is how author describes core of his discovery: “Broken DNA causes genome instability, which distracts the Sir2 protein, which changes the epigenome, causing the cells to lose their identity and become sterile while they fixed the damage. Epigenetic changes cause aging. There was, I imagined, a singular process that controlled them all. Not a countless number of separate cellular changes or diseases. Not even a set of hallmarks that could be addressed one at a time. There was something bigger—and more singular—than any of that. This was the foundation for understanding the survival circuit and its role in aging.“
The main analogy of this chapter is piano as DNA and epigenome as Pianist. The failing of SIR proteins allows accumulation of errors in epigenome, so pianist becomes demented, even if piano is good. Author discusses it in details and provides graphic presentations:

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The main point that author makes here is that, as disease, aging is susceptible for treatment and that is what author is working on and he believes that such treatment is possible.

Part II: What We’re Learning (The Present)

Chapter 4. Longevity Now

Here author presents what is known about longevity and various examples of it occurring. He provides some recommendations: fasting, food mix, exercise, a bit of cold exposure, and so on. However he admits that the most important factor is good DNA.

Chapter 5. A Better Pill to Swallow

Here author moves a bit to philosophy and history, discussing Gilgamesh, Schrodinger, and nature of life. Then he moves to biology presenting:” The three main longevity pathways: mTOR, AMPK, AND SIRTUINS, evolved to protect the body during times of adversity by activating survival mechanisms. When they are activated, either by low-calorie or low-amino-acid diets, or by exercise, organisms become healthier, disease resistant, and longer lived. Molecules that tweak these pathways, such as rapamycin, metformin, resveratrol, and NAD boosters, can mimic the benefits of low-calorie diets and exercise and extend the lifespan of diverse organisms.
. He also discusses resveratrol and some other compounds.

Chapter 6. Big Steps Ahead

Here is graphic representation what author believes in achieving:

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And here is the way author plans to achieve this:

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Chapter 7. The Age of Innovation

This chapter is about the last centuries of innovation in medicine. It starts with discussion of DNA and diagnostic and treatment feasts it made possible. Then author moves to more technical discussion about tools summarizing this in this picture:

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Part III: Where We’re Going (The Future)

Chapter 8. The Shape of Things to Come

Here author looks at what will happen if his anticipation of elimination of aging in near future would come true: lifespan and health span extended beyond 100, leading to families of 4-5 generations, stress on resources, slowing down of scientific and political progress because individuals in power live a lot longer, social insecurity, renewed Malthusian challenge, and so on. However author ends the chapter on semi-optimistic note that humanity managed to overcome challenges before, so there is a chance that it would overcome this one too, especially if it means population of healthy, active, and productive 100 year olds.

Chapter 9. A Path Forward

The last chapter ends book with standard pitch of contemporary science: “we are about do and make great things, just give us more public money. No, make it a lot more public money”. In this particular case it sounds like complain that other get more for various diseases with really not that big impact, while aging impacts everybody and treatment of this disease would fix all others such as:

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The final point here is that people should be able to die when they want to die and be healthy and productive until this moment.

Conclusion

In conclusion author describes his and his team current activity and stresses that so far there is no approved treatment for aging. However he can share what he himself does to prevent this disease:

  • 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.
  • 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 analyzed 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. If I work out, I will eat meat.
  • I don’t smoke. I try to avoid microwaved plastic, excessive UV exposure, X-rays, and CT scans.
  • I try to stay on the cool side during the day and when I sleep at night.
  • I aim to keep my body weight or BMI in the optimal range for healthspan, which for me is 23 to 25.

MY TAKE ON IT:

I think it would be wonderful if author is correct and his research would lead to elimination of the most profound and most dangerous epidemic that kills 100% of people impacted – aging. I would not hold my breath in anticipation of this, but I believe that a number of point here are valid:

  • Epigenetic nature of aging rather than DNA error accumulation
  • Potential for regular maintenance of this epigenetic environment that would eliminate or greatly diminish symptoms of aging.

However I do not believe that lifespan extension would be a problem economically or environmentally. Economically advance of Artificial intelligence will eventually make humans redundant for production of goods and services, freeing them to pursue happiness as the main business of live. Environmentally it would also not going to be a problem because we are getting closer and closer to finalizing stable level of population and establishing complete control over environment by setting up closed loop of production/consumption and controlling additional inputs/outputs into the system, including most important: solar radiation. In short the future is bright and we’ll probably see a glimpse of it.

 

 


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