The Four Horsemen
Understanding the four chronic diseases that kill 80% of people within industrialized nations.
Life and Death
Within industrialized nations, there are four diseases, or more specifically types of disease, that kill an overwhelming majority of the population (~80%). Since we will probabilistically die from one of these diseases eventually, a large part of extending our lifespan boils down to finding a way to delay the onset or mitigate the likelihood of these diseases.
By doing so, we achieve three key benefits; 1) Extend the duration of our lives (increase lifespan); 2) Increase the quality of our lives (increase healthspan); and 3) Minimize the time, or percentage of our lives, spent in a state of suffering that underpins these diseases. The function below with lifespan (years lived) on the horizontal axis and healthspan (quality of life) on the vertical axis portrays these three benefits.
The blue arrow represents benefit number one above, which is an increase in total lifespan. In this theoretical example, life has been extended by 10 years. Of equal, if not higher, importance is the change denoted by the red arrow, which is an increase in healthspan. If we think of the curves as the lives of two different people, who is living a better quality of life at age 70? Of course, it's the person following the top curve.
They found a way to retain much more of their mental and physical function and thus maintain greater control and independence for a longer period of time leading to a much higher quality of life. In comparison, the person following the bottom curve is losing their independence at an exponential rate and, as a result, spending a much longer period of time living a lower quality life. This leads to the third benefit which is minimizing the percentage of our lives that is spent in a state of suffering or suboptimal living.
Graphically, this concept is represented in the tails of the two curves, as the lines approach zero on the horizontal axis, where the top curve has a steeper slope than the bottom curve. The top curve shows a longer life of which the majority was lived in or near peak physical and mental condition with a sharp decline, ranging a couple of months to a year, and quick death.
Contrasted with the life of a person on the bottom curve who spends two decades, or 25% of their life, between the ages of 60 and 80 losing key functions at an increasing rate. Which curve would you rather ride?
Translating graphs and theories into practice, this means that the individual who figures out a way to ride the top curve will be walking, socializing, cooking, driving, bathing, dressing, and otherwise able-bodied and living independently while their less informed comrades file into nursing homes to have others perform these functions for them.
Whatever it is that you want to be able to do in your seventh, eighth, or ninth decade, you have to start living a lifestyle now that will allow you to do those things in the future. The five levers outlined in The Longevity Framework guide our strategy and inform our tactics to align our lifestyles with the goal of increasing longevity (lifespan + healthspan).
One of the most essential aspects of achieving this goal is finding a way to delay the onset or minimize the likelihood of the four diseases this article will introduce. If we can find a way to do so, we’ve won half the battle of living a longer and healthier life.
Now, onto the horsemen. In order of mortality rate, highest to lowest, the four diseases that kill the vast majority of those living in industrialized nations are:
Atherosclerosis (i.e., Cardiovascular disease, Cerebrovascular disease)
Neurodegenerative disease (i.e., Alzheimer’s disease)
Metabolic disease (i.e., NAFLD, NASH, IR, T2D, hyperinsulinemia)
The three predominant categories of chronic disease, atherosclerosis, cancer, and neurodegenerative disease, all have strong links to underlying metabolic diseases. In other words, metabolic diseases are rarely the cause of death but are massive contributors to the development of the other three diseases which are.
Atherosclerotic diseases, such as coronary heart disease (heart attack) and cerebrovascular disease (stroke), are defined by the thickening or hardening of arteries caused by a buildup of plaque in the walls of the arteries. Over time, this buildup narrows the arteries which make it difficult for blood to flow through. If a blood clot forms as a result of ruptured atherosclerotic plaque, which is responsible for 99% of heart attacks in the U.S., blood flow may be blocked causing a heart attack or a stroke.
Combined, diseases of atherosclerosis are the leading cause of death in industrialized nations, followed by cancer, although that gap is narrowing. Compared to cancer and neurodegenerative disease, we have the best understanding of atherosclerotic diseases from a prevention, risk assessment, diagnosis, and medical intervention standpoint.
Diseases of atherosclerosis are time exposure diseases, meaning that risk increases the longer you are alive. Because of this, there is a compounding nature to atherosclerosis, which means that there is a higher risk of an incident from atherosclerosis going from your 50s to your 60s compared to going from your 30s to your 40s.
Cardiovascular disease (CVD) is the blanket term for diseases that impact the cardiovascular system which is the system responsible for the circulation of blood, and everything blood contains, throughout the body. The most common types of cardiovascular disease are coronary heart disease (heart attack) and cerebrovascular disease (stroke).
While discussing atherosclerosis, actual or perceived, with your doctor there are two key questions that should be discussed: “How do I feel?” (presence or absence of symptoms) and “Is this going to impact how long I live?”. Common risk factors of CVD are smoking, diabetes, a lipid disorder such as severely elevated LDL cholesterol levels, and, as mentioned previously, age.
Although atherosclerosis progression over time is inevitable, the speed at which it progresses is partially up to us. We can alter conditions in our favour, such as sleep, nutrition, and exercise, in order to reduce the rate at which plaque accumulates.
Shockingly, 50% of women and 33% of men in the U.S. will be afflicted with cancer in their lifetime. Within Canada, the Canadian Cancer Society expects 43% of women and 44% of men to develop cancer in their lifetime. Although risk often increases with age, similar to atherosclerosis, cancer lethality is highest among those aged 45 to 65, killing more people in that age range than heart disease, liver disease, and stroke combined.
Cancer can originate from three places, including outside the body (i.e., melanoma, colon cancer), inside the body (i.e., brain cancer, prostate cancer), and in the blood (i.e., leukemia). Aside from taking actions to prevent cancer, screening for cancer thoroughly and often in order to detect it early is one of the most important things we can do to reduce the likelihood that, if we develop cancer, it will be life-ending.
It’s useful to think about cancer in a three-step framework. Step one is to try not to get cancer. Start with the low-hanging fruit by not smoking and maintaining a healthy weight. Step two is to look for cancer early. Screen aggressively and often. How to screen is a topic probably best discussed with your doctor. Step three would be to, if cancer exists, use therapies that go after multiple pillars simultaneously (i.e., immune system, epigenetic regulators, growth factor receptors, metabolism).
In the case where one develops cancer, there are three pillars to treating it: chemotherapy, radiation, and surgery. Chemotherapy attempts to solve the paradox of killing the cancer cells while not killing non-cancer cells. In fact, it’s not difficult to kill cancer cells. Bleach, formaldehyde, and most chemicals on the shelf at Home Depot are able to kill cancer perfectly. The problem is that they kill everything perfectly.
To solve this riddle, chemotherapy attacks the things in our bodies that grow, preferably targeting the cancer cells, which explains the reason for hair loss during chemo treatment. Radiation is a useful tool to locally control cancer, meaning to stop cancer growth at the place of origin. Lastly, surgery is a procedure performed to cut out cancerous masses such as tumors.
Again, if cancer does exist this should be a point of discussion with your doctor. For more information on this framework, visit its origin which was a conversation between Dr. Keith Flaherty and Dr. Peter Attia.
Dementia is the umbrella term that categorizes diseases recognized by a change in memory or other areas of cognition. The key indicator in the development of these diseases is a change from a previous state (i.e., not born with it) that interferes with day-to-day function. There are many types of dementia, however, Alzheimer’s is the most common and thus will be one of our main focuses in this area going forward.
Almost everyone knows someone who has been afflicted with Alzheimer’s disease. Based on that anecdotal evidence we can all agree it’s one of the most disheartening and despairing diseases to watch a loved one endure. Although we won’t all suffer from dementia, nearly all of us will die with some form of cognitive impairment.
Instead of letting this depress us, we should use that knowledge to inform our life philosophy. Don’t wait for someday. Do the important things, the things you dream to do, now while you still have the chance to experience them with full cognitive and physical function. How well we feel we’re aging is impacted by how much regret we live with, so don’t leave any room for regret in your life.
The only thing that can make watching someone living with dementia more depressing is having the knowledge that they didn’t live the life they wanted to. So, get out there and start living.
Common metabolic diseases include nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), insulin resistance (IR), type two diabetes (T2D), and hyperinsulinemia. Although people generally don't die directly from these diseases, they contribute heavily to the development of atherosclerosis, cancer, and neurodegenerative disease.
Metabolic diseases are closely associated with being overweight and having an inactive lifestyle and are often linked to a condition called insulin resistance. Although we’ll dive deeper into these topics later on, it’s important to note that losing weight, exercising, and making healthy dietary changes are critical in improving your metabolic health.
The purpose of this article is intended to be a brief introduction to four incredibly complex diseases that are omnipresent in our society. Our understanding of these diseases is constantly changing as new research emerges. Nearly everything must be talked about probabilistically when engaging in discussion regarding health in general and certainly within the domain of these diseases.
Beginning with an awareness and basic understanding of these diseases allows for future discussion regarding how we may go about preventing, diagnosing, and treating each of these diseases. The scope of the Longevity Minded Newsletter will focus more on the prevention aspect as that is where I feel I can provide the most value to you.
The diagnosis and medical intervention of these diseases are tremendously complex to understand, let alone try to accurately simplify and disseminate for the comprehension of those lacking scientific or medical backgrounds. Future newsletters will work to further demystify these diseases to which, as a society, we are largely ignorant and uninformed due to cultural taboos and gaps in the education system.
Gearing your lifestyle towards the first three levers, sleep, nutrition, and exercise, will put you leaps and bounds ahead of the general population in mitigating your risk for these diseases.
Next week we’ll cover Lever #2: Nutrition, its five sub-levers, the simplest way to transition away from the Standard American Diet, and the cult-like mentality around dietary restriction.
And, as always, please give me feedback on Twitter or by hitting reply to this email.
What a great recap, reduced down to essentials. I've never seen longevity medicine expressed in this way - so clear!