Notes on

Longevity...Simplified: Living a Longer, Healthier Life Shouldn’t Be Complicated

by Howard J. Luks, MD


Healthspan is the period of time you are cognitively intact and physically able. This is what matters — lifespan (time alive) is not enough. We want to do more than just be alive, we want to live.

The book emphasizes simple, actionable, evidence-based strategies that work.
These have been shown to improve metabolic health, reduce chances of suffering from many chronic diseases and early demise.

The strategies include:

  • Create a caloric deficit, then stay lean.
  • Get sleep.
  • Eat real food.
  • Move often, throughout the day.
  • Push and pull heavy things.
  • Socialize.
  • Have a sense of purpose.

The underlying goal for achieving a longer healthspan is metabolic health.
Your metabolic health correlates with your overall health.

The changes you need to make aren't particularly drastic, either.
For example, nearly 40% of yearly dementia cases are preventable by improving our diet, sleep, and exercise regimen — all factors improving our metabolic health.
To make these improvements, you could walk 6,000 steps (or more), eat more nutritious food, sleep at least 7 hours a night, and do resistance training (e.g. bodyweight).

Metabolic health

Suboptimal metabolic health serves as the fundamental source of numerous chronic illnesses we experience.
Examples include metabolic syndrome, stroke, dementia, type 2 diabetes, and various cancers, all of which share poor metabolic health as the primary underlying factor.

You are metabolically healthy when you have ideal

  • blood sugar levels,
  • Insulin levels,
  • Blood pressure,
  • Blood lipids (triglycerides, high-density lipoprotein (HDL), cholesterol), and
  • Have no abdominal obesity.

It's important to realize that you can be of "normal" weight, yet still not be metabolically healthy. You can be overweight but metabolically healthy.

The longer you have metabolic health issues for, the worse it is. This also means, if you are currently metabolically unhealthy, you should hurry up and get healthy. Time is quite literally of the essence.

Being metabolically healthy isn't about speeding up a "slow" metabolism. You can't do that; the hypothalamus controls it. Our basal metabolic rate is rather stable, no matter whether you're active or sedentary.

You can, however, improve your metabolic health by

  • improving your diet,
  • increasing muscle mass,
  • moving more, moving often, and
  • increasing your aerobic fitness.

Triglycerides

High triglyceride levels is as harmful as having high LDL cholesterol levels.

Improving your metabolic health → improves your insulin resistance → enhances your ability to store glucose as glycogen → decreases the glucose the liver needs to contend with → lowers triglyceride levels.

How glucose metabolism works (only some of this is described in the book. I wanted to understand the entire process. I am NOT a doctor — this may very well be wrong):

  1. When you eat carbohydrates, your body breaks them down into glucose. This is absorbed in your intestines and distributed into your bloodstream, which carries it to all the cells in your body.
  2. Some of the glucose is taken up by the liver. This amount depends on the current energy needs of your body.
  3. The liver stores glucose in the form of glycogen (large, branched polymer of glucose residues). This acts as a buffer for blood glucose levels. When your body needs a quick burst of energy, the liver can break down glycogen back into glucose and release it into the bloodstream.
  4. The liver's capacity to store glucose as glycogen is limited. Once glycogen stores are full, if the body still has excess glucose (typically from overeating carbohydrates), the liver will convert glucose into triglycerides (a type of fat) in a process called de novo lipogenesis. This process involves a number of steps:
    1. Glucose (a 6-carbon sugar) is converted into pyruvate (a 3-carbon molecule) through glycolysis. This happens in the cytoplasm of your cells. Here, glucose is split into two molecules of pyruvate (a 3-carbon molecule), releasing a small amount of energy that the body stores as ATP (adenosine triphosphate). This is the main currency your cells use for energy.
    2. Pyruvate enters the mitochondria and is converted into a compound called Acetyl-CoA.
    3. Multiple molecules of Acetyl-CoA can then be combined together to form fatty acids
    4. These fatty acids are combined with a molecule called glycerol to form triglycerides
  5. Once formed, triglycerides can be packaged into very low-density lipoproteins (VLDLs) and released into the bloodstream. These can be taken up by fat cells (adipocytes) and stored as fat.
  6. As these VLDLs pass through your body, an enzyme called lipoprotein lipase, present on the blood vessels, breaks down these triglycerides into free fatty acids and glycerol. These components can then be absorbed by nearby cells (like muscle cells for energy or fat cells for storage).
  7. After the triglycerides have been removed from VLDLs, the lipoproteins decrease in size and become low-density lipoproteins (LDLs). LDLs contain a higher proportion of cholesterol than VLDLs because most of the triglycerides they were carrying have been removed.

That is, VLDL becomes a cholesterol molecule. The more triglycerides you have, the more LDL cholesterol.

LDL is considered "bad" cholesterol because high levels of LDL cholesterol can lead to plaque build-up in your arteries, which can lead to heart disease.
As usual, the entire story is more nuanced than just good & bad. LDL's role is to transport cholesterol to the cells that need it, and cells use cholesterol for various functions. Be careful of branding something as evil just because you've heard of it as such in various contexts.

Insulin resistance

Insulin resistance is a condition where cells in the muscles, fat, and liver don't respond well to insulin, a hormone made by the pancreas that helps glucose in your blood enter cells in your muscle, fat, and liver, where it’s used for energy1 . As a result, glucose can't easily enter the cells and builds up in the bloodstream. To compensate for this, the pancreas produces more insulin to help glucose enter the cells12. Over time, the pancreas may not be able to keep up with the demand for insulin, leading to high blood sugar levels and prediabetes or type 2 diabetes13.

Insulin resistance is often associated with high blood pressure, high lipids (triglycerides), type 2 diabetes.

Even young people who are thin can be insulin resistant.

The sooner insulin resistance is recognized, the sooner you can take measurements to prevent chronic metabolic conditions, such as type 2 diabetes.

Insulin’s resistance isn’t good. It leads to all kinds of bad diseases. To prevent it, lower caloric intake and exercise more.

There are multiple ways to prevent/deal with insulin resistance, and each should be followed:

  • Decrease overall caloric intake
  • Increase exercise & muscle mass to burn more calories

The end result is healthier mitochondria, which enables our muscles to take more glucose out of our bloodstream.

Visceral fat

Belly fat, or visceral fat, is metabolically active and wreaks havoc on our metabolism.
It increases our systemic inflammation, and its presence is strongly associated with the development of heart disease, stroke, type 2 diabetes, and Alzheimer's disease.

Neurodegenerative disease

  • We cannot prevent Alzheimer's disease & other forms of dementia, but we can lower the risk of developing it.
  • Belly fat can lead to Dementia, Alzheimer's disease.
  • We want to keep our homocysteine levels low by ensuring we get enough B vitamins — to fight against Alzheimer's disease.
  • The number one way to decrease risk of developing dementia is to remain in proper metabolic health for as long as possible.
  • Exercise is a proven intervention that lowers risk of developing dementia. Exercise and muscle mass dramatically affects our risk of developing many chronic diseases, including dementia.
  • Get adequate amounts of sleep.

Heart disease

This is challenging to identify. Some well-established risks for cardiac disease are:

  • Poor sleep habits.
  • Poor dietary choices.
  • Smoking.
  • Hypertension (high blood pressure).
  • Chronic intake of NSAIDs (non-steroidal anti-inflammatory drugs).
  • Your innate desire to perform better (stress).

The subtle signs are easy to miss, but can be indicative of big issues. Few would see a doctor with symptoms of heartburn that occurred with exercise — but you should. Few would consider seeing a doctor for nausea which routinely happens on long runs — but you should.

The classic, mainstream presentation of crushing chest pain isn't as common as you think (especially in women).

Some subtle signs that a cardiac event might be forthcoming:

  • Fatigue—when you’re more tired and not performing as well as usual—you may be short of breath with activities that were easy to achieve previously.
  • Nausea—many of us bonk or crash, get side-stitches, etc. on routine hard days, but new symptoms or new-onset nausea associated with effort should trigger at least a discussion with a healthcare professional.
  • Neck, chest, or left arm discomfort associated with training

Inflammation and high LDL levels are key drivers of heart disease risk. Diet, stress levels, sleep, and family life have a lot to do with the amount of inflammation our body is subjected to.

Many chronic metabolic diseases like type 2 diabetes increase our systemic inflammation.

Known risk factors for heart disease:

  • Increasing age.
  • Lack of sleep.
  • Family history of cardiac issues (Lp(a)).
  • Hypertension (high blood pressure).
  • LDL cholesterol and your ApoB levels.
  • Obesity and type 2 diabetes.
  • An inflammatory diet high in ultra-processed foods and low in grains and veggies.
  • Psychological and physical stress.

Sleep

Poor sleep can lead to heart disease, cognitive decline, dementia, insulin resistance, and a decrease in your immunity.

Getting enough sleep is critical.

Not getting enough sleep leads to...

  1. Increases your blood pressure.
  2. Increases the debris in your brain that leads to dementia.
  3. Increases your insulin resistance and blood glucose.
  4. Decreases your testosterone.
  5. Decreases your immune system, specifically your natural killer cells (T-cells).
  6. Increases your risk of developing atherosclerosis.
  7. Decreases your ability to learn the next day.
  8. Decreases your ability to store memories from the previous day
  9. Reduces your ability to build new muscle protein.

One night isn't what'll get you, so don't get anxious about one bad night. You should only start worrying if it becomes a pattern.

You need 7-8 hours of sleep. You aren't unique. You don't need less, no matter what hustle-culture tells you.

Tips for better sleep

  • Establish a regular sleep schedule to set your circadian rhythm. Outdoor activity and exercise helps.
  • Get early morning exposure to outdoor light to strengthen your circadian system. Look towards the sun (not at!) without glasses on. The brightness affects hormones produced in the brain which help regulate your circadian rhythm in the morning. Ideally do this at the same time daily.
  • Create a winding down routine before bed, such as dimming the lights (2 hours before bed), taking a hot shower, stretching exercises, meditating, or reading. No video games or checking social media.
  • Avoid emotional stimulation from social media or news sites before bed.
  • Refrain from heavy alcohol consumption two-to-three hours before sleep. Also, avoid smoking or chewing tobacco. Alcohol doesn't help you sleep, it greatly reduces your sleep quality.
  • Avoid caffeine 12 hours prior to bedtime.
  • Refrain from eating heavy, spicy, or sugary foods 2-3 hours before bedtime. A light, non-sugary snack is acceptable.
  • Engage in regular exercise, but not right before bed.
  • Limit daytime naps to 25-35 minutes, preferably around 3:00 - 4:00 p.m.
  • Use comfortable, inviting bedding.
  • Keep the bedroom temperature between 65-67°F and well-ventilated. Your body temperature needs to drop to help trigger sleep hormones (so taking a hot shower can help, due to the cooling effect after).
  • Minimize noise and light in the bedroom by blocking out distractions.
  • Reserve the bed for sleep and sex only, to train your brain to associate the bed with sleep.
  • Discuss your worries and stress with others to avoid going to bed anxious.
  • You can talk to your doctor or pharmacist about sleep supplements, like melatonin.

And a few things to avoid:

  • Drinking yourself to sleep.
  • Sleeping pills.
  • Antihistamines.

Nutrition

  • Eat real food.
  • Eat less food
  • Get enough fiber in your diet to support your gut

What we eat is a common cause of metabolic dysfunction. In particular, it's the amount of calories we consume, and the foods which contribute to this caloric burden.
Our big problem is that we eat too much, too often. And that we often eat the ultra-processed stuff isn't helping.

Ultra processed foods → high calorie burden → poor diet → metabolic dysfunction → chronic disease.

Take care of your diet.

You don't need to follow some crazy diet. Just be more mindful of what you put in your body.

  • Eat less sugar.
  • Prefer unsaturated fats over saturated fats.
  • Eat more plants.
  • Avoid ultra-processed carbohydrates (e.g. cereal, instant oatmeal, white rice)
  • Include more fiber from vegetables and fruits

Elimination diets aren't necessary, nor healthy. What matters is lifestyle.
Fad diets don’t work.
Say no to elimination diets; say yes to lifestyle changes. That is what is most sustainable. But it’s not easy. At all.
Avoid overweight. If you are, then get in a caloric deficit to lose weight.

The gut & microbiome

  • The benefits of a high-fiber diet mainly come from soluble fiber, impacting the gut microbiome positively.
  • Our gut contains trillions of bacteria, including many species that are beneficial to our health.
  • The gut plays a vital role in our overall health, even contributing to 75% of dopamine and serotonin used by brain nerve cells.
  • The food we consume feeds our gut microbiome, with bacteria breaking down these foods into components that we absorb. Many of these components are beneficial to our health.
  • A diverse and healthy gut microbiome is often seen in those who maintain a good diet. In contrast, those who consume a standard American diet usually have less diverse gut microbiomes, leading to a higher risk of various diseases.
  • Adjusting our diet can help rebuild the diversity of our gut microbiome, which is an area of ongoing research.

Fat isn't bad

You're told that fat is bad. Now, so many things are low-fat, and instead contain ultra-processed carbohydrates. This is a horrible deal for us.

Not all carbohydrates are good, and not all fats are bad.

Avoid trans fats. Avoid saturated fats. Eat unsaturated fats.

High-fat diets probably aren't great, but fat is a whole isn't as big an issue as ultra-processed carbohydrates.

Just be careful: low-fat doesn't mean healthy.

Good carbohydrates

These are complex carbohydrates like plants: nuts, vegetables, fruits. For example, beans, oatmeal, walnuts, apples, bananas, and carrots.

These take longer for your body to metabolize, meaning they have a lower glycemic index due to the slower absorption in your intestines.

What should you do when you have an elevated triglycerides/HDL ratio?

Eating too many ultra-processed carbohydrates can cause elevated triglycerides. Those of us with elevated triglycerides/HDL ratio are at higher risk of chronic disease. To decrease the amount of triglycerides you produce, you can

  1. Reduce consumption of ultra-processed carbohydrates (sugars) and overall calories, and
  2. Increase the number of calories you burn.

The carbohydrates you should limit are simple, highly-processed carbohydrates like white bread, white rice, sugar, pasta, bagels, cookies, etc.

Most of us, assuming total caloric intake is under control, can eat the following in moderation: complex carbohydrates like natural whole grains, beans, legumes, and nuts.

Complex carbohydrates lead to less rapid absorption of glucose into our bloodstream. It's the fiber that comes along with the complex carbohydrates and berries matter in this context.

Quick hits

  • A study in Current opinion in clinical nutrition and metabolic care showed that adequate protein (25-30 grams) needed per meal, three meals per day is important for muscle protein synthesis as we age.
  • Essential amino acids must be consumed in the diet, as the body cannot create them.
  • Aging reduces ability to respond to low doses of essential amino acids. However, leucine supplementation increases protein synthesis in elderly.
  • Insulin resistance progresses to type 2 diabetes, not because you consume too many carbohydrates, but because you eat too many calories overall. So don't just 'avoid carbs.'
  • Fructose is not healthy for you. So, most sports drinks (and similar) aren’t healthy either. Avoid them. You basically only need sugary drinks when running further than 15 miles. You don’t need Gatorade, you need water.

Exercise

When you’re feeling stressed, depressed, or anxious go for a walk. Exercise is the best medicine. It will boost your mood.

We only need to walk for 15-20 minutes a day to see the benefits of exercise.
Only 6,000 steps a day correlates with a significant decrease in all-cause mortality.

People who are more physically fit tend to live longer.
A study, Association of Cardiorespiratory Fitness With Long-term Mortality Among Adults Undergoing Exercise Treadmill Testing, found a direct correlation between fitness level and decreased disk of dying from anything (all-cause mortality).

Studies have found 30% decrease in mortality if you exercise 120 minutes a week at a moderate pace. 19% improvement if you perform a less vigorous physical activity (e.g. walking around every few hours). 39% decrease in mortality in those who do 1 hour of moderate-intensity exercise each day — this seems to be the maximum gain we can achieve with exercise alone.

It's better to be active all day — a single bout of exercise followed by a day on the couch doesn't improve markers of Metabolic health.
E.g. walk in the morning, park in the farthest parking spot, always take stairs, evening walk.
Sitting for hours on end can negate the benefits of a 30-minute run earlier in the day.
Even getting up and walking around the office for a minute every 30 minutes, or holding a walking meeting with a colleague, will do the trick.

Move more, move often, and move occasionally with ferocious intent.

A complete exercise program has four pillars:

  • Aerobic training
  • Resistance training
  • Balance training
  • High-intensity training (HIT)

These are mostly the same pillars as those mentioned in Outlive.

Aerobic training

Most of your aerobic training should be around zone 2 (or very low zone 3). Base building involves you being in this area.

Overtraining is a serious problem. We think we need to go hard every time we work out, but that’ll lead to overtraining, poor results, and injury.

Base building

Base building is getting your heart and lungs ready to do an exercise program. It's about improving your body's efficiency and ability to put down a certain distance, at a certain pace, while using less oxygen and less energy.

It primarily involves low heart rate training. Base building takes months. Don't run too hard too fast. Otherwise, you risk injury.

The target is 70% of your maximum heart rate or lower. Any higher is too painful & too stressful.

If you don't have a HR monitor, your can test by whether you're able to carry on an easy conversation without having to catch your breath.

Say you want to start running. You could do base building like this:

  • Start by being able to walk at a brisk pace while controlling your intensity.
  • Then transition to running: run-walk 1 mile 3 times a week, staying in the appropriate zone (2, HR around 65%-70%). But might be best to start by walking and controlling intensity, then adding running after a week or two.
  • Slowly incorporating more running than walking, but staying in the same HR zone. You should be able to carry a conversation.

The next step is to build up with 10%-15% weekly, until you reach 5k. This is about the threshold your heart, lungs, bones, and tendons can handle.

Elite athletes spend months Zone 2 training (or, base building). At least 75-80% of their active training is in Zone 2 as well. Train like the athletes.

🏃‍♂️ Zone 2
  • In Zone 2, the body primarily burns fat for energy and has sufficient oxygen for its needs.
  • The body's most efficient way of obtaining energy is through burning fat, a process that occurs within the aerobic metabolism framework.
  • There is a limit to the level of activity that can be powered through fat alone.
  • Upon moving into Zone 4, the body begins to produce energy through anaerobic pathways due to increased exertion.
  • In this state, the oxygen demand rises significantly, and the supply can't keep up, resulting in more challenging breathing.
  • The body starts using glucose for energy, but without enough oxygen, this process becomes anaerobic.
  • In an anaerobic state, glucose provides less energy, and by-products like lactic acid build up in the muscles.
  • This lactic acid build-up hinders the cells' ability to sustain the activity, causing muscle fatigue, soreness, swelling, and ultimately limiting the duration at which this pace can be maintained.

After base building, you can start adding other types of runs. But you should still continue to do base building (run in zone 2) weekly.

You're now more efficient at creating and utilizing energy stores.

Try to spend 90 min in zone 2, twice a week. This should increase your Zone 2 fitness.

Balance work

Balance work is very important. It'll help you reduce injuries by improving balance. Mobility and strength is linked to healthspan. It doesn't require elaborate gym-based programs. E.g. standing on one leg for 30 seconds. Then progressively, as you get better, make it harder. You can do that by moving your arms while balancing. Switching legs every minute. Carrying small objects or weights.

Rest & recovery

Prefer active rest over absolute rest — a few weeks of no exercise & you are set back months in terms of the level at which you were training. The consequences of even a few weeks of inactivity or rest are dramatic: your body chemistry changes, your muscles change, and your heart and lungs decondition significantly. Run Like a Pro talks about this as well

How to recover: Usually, the day after a particularly long walk, ride, or jog, your heart rate is a little higher, or perhaps you're a little short of breath. Then it's time to have a lighter day. Recovery is relative — rode 40 miles yesterday? Do 4 miles today. Jogged 5 miles yesterday? Walk 1 mile today. Let your body completely rest from resistance or pushing your aerobic thresholds one or two days a week. But prefer active recovery — walk, hike, etc. Let your heart and muscles recover and repair themselves from your activity over the past week.

Resistance training

Resistance training is a must for increasing healthspan as it helps ward off sarcopenia (the gradual loss of muscle mass and strength that occurs with aging).

  • Muscle mass is crucial for performance, longevity, and healthspan
  • Loss of muscle mass predicts worse recovery after injury/surgery
  • Muscle tissue is > 50% of body mass, essential for metabolic health
    • Muscles help control glucose levels, and uses glucose as fuel
    • Muscles reduce risks of insulin resistance and type 2 diabetes
  • Loss of muscle mass leads to fatigue, loss of function, disability, fall risk, frailty, and death.

You should emphasize leg exercises. Push & pull heavy things.

Exercise can increase the at at which your muscles take up glucose, even in the presence of insulin resistance.
This further diminishes the amount of glucose in your bloodstream, leaving less excess glucose for the liver to make triglycerides.
Less glucose in your blood decreases the signal to the pancreas beta cells to produce insulin, reducing insulin concentration in your blood.
The lower your insulin level, the healthier you are.

Muscle mass is also linked to a decrease in all-cause mortality. The more muscle you have, the smaller your risk of dying from a chronic disease.
Just one hour of resistance training a week can lead to a decrease in all-cause mortality.

To build muscle, you should focus on:

  • diet, eat enough protein - at least 1.6 g per kg you weigh.
  • resistance training
  • (optional) dietary supplements, e.g. creatine

Markers to monitor

  • LDL
  • Triglycerides
  • Cholesterol
  • HbA1c
  • Homocysteine
  • Uric acid
  • & other basic biomarkers

This is essential. It gives you a snapshot of how your dietary, sleep, and exercise habits shape your risk of developing chronic disease.

The following biomarkers should be checked annually to determine your metabolic health:

  • Waist Circumference: < 102 cm for men or 88 cm for women / < 40 inches for men or 35 inches for women.
  • Systolic Blood Pressure: < 120 mmHg (when it comes to your blood pressure readings, systolic matters the most).
  • Diastolic Blood Pressure: < 80 mmHg.
  • Fasting Glucose: < 100 mg/dL.
  • HbA1c: < 5.7%.
  • Triglycerides: < 150 mg/dL.
  • HDL-C: >= 40/50 mg/dL men/women.
  • Cholesterol preferably under 180.
  • Lp(a): Responsible for perhaps 15% of heart attacks at a young age. Normal levels are under 30 mg/dl.
  • ApoB vs. LDLc: ApoB tracks your risk of heart disease better than LDL- levels under 70 are optimal.
  • Uric acid: Uric acid levels can indicate high blood pressure and issues other than only gout. Levels under 5 are optimal.
  • Homocysteine: Some studies speak to the risk of dementia and arterial damage if these levels are high. In a healthy person, homocysteine levels are around five to 15 micromoles per liter (mcmol/L).
  • Resting pulse: In general, the lower your resting heart rate, the healthier you are.

Make your day harder

This is a pretty good principle.

Make your day harder to live longer & better.

  • take the stairs, not the elevator.
  • park further away from the store.
  • go for a walk during lunch break.

And so on. Just get some wins during the day.

Supplements

Creatine may have a role in improving our brain's energy systems.
Energy generation via the mitochondria seems to be a final common pathway for the development of dementia.

Supplementing with creatine is proved to be a safe and effective way of minimizing age-related muscle loss and cognitive decline.

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