Mitochondrial Biogenesis and Metabolism: The Cellular Foundation of Health

Mitochondrial Biogenesis and Metabolism2

Mitochondrial biogenesis and metabolism are the gateways to the cellular foundation of health, and are built by the food you eat, the activity you do and how they impact mitochondrial biogenesis and metabolism. Learn what to do to keep your cells energized as you age.

Mitochondrial Biogenesis and Metabolism2

T2DM is Type 2 diabetes

We commonly think of metabolism in terms of “metabolic rate”, as in “My metabolism has slowed down”, or “She has a fast metabolism; she can eat anything and not gain weight”.

In that context, the typical understanding of metabolism is that it’s something that runs the engine of our body. If it’s fast, you might be lean; slow, you might be overweight.

Some of us know a bit more about metabolism than that. We know that there are various metabolic markers that can depict the health of your metabolism, such as blood pressure, fasting and average glucose, waist circumference, and triglycerides. In fact, having any three of those markers defines the unhealthy and very much unwanted “metabolic syndrome”.

But there’s even more to metabolism than all of that. If you follow the chain of biochemical events that transform the foods you eat into what our cells actually use for fuel — ATP — then you can glean the totality of what metabolism is, which in a nutshell is: All the biochemical processes that maintain life.

Seems kinda of important, yes?

Which is why I want to share with you a lean, to-the-point outline about metabolism (from the food you eat to the manufacture of ATP), including why it matters, what happens to it as you age, and how to have a healthy metabolism.

Here’s what I cover:

Let’s dig in…


Part 1: Definitions of Key Concepts

  • Metabolism: The sum of all chemical processes that occur within a living organism to maintain life, involving anabolism (building up) and catabolism (breaking down) of substances.
  • Metabolic Rate: The rate at which the body expends energy or burns calories.
  • Metabolic Syndrome: A cluster of conditions (increased blood pressure, high blood sugar, excess body fat around the waist, and abnormal cholesterol or triglyceride levels) that occur together, increasing the risk of heart disease, stroke, and diabetes.
  • Energy Balance: The state achieved when energy intake (through food) equals energy expenditure (through basic metabolic processes and physical activity).
  • Mitochondria: Organelles within cells responsible for producing ATP (adenosine triphosphate), the cell’s main energy carrier.
  • ATP (Adenosine Triphosphate): The primary energy currency of the cell, used to power various biological processes.
  • Mitochondrial Biogenesis: The process by which new mitochondria are formed within the cell, enhancing the cell’s capacity to produce ATP.


Part 2: Methods to Measure Metabolic Rate

  • Basal Metabolic Rate (BMR): The amount of energy expended while at rest in a neutrally temperate environment, measured through indirect calorimetry. (Watch this 3:25 minute video.)
  • Resting Metabolic Rate (RMR): Similar to BMR but slightly higher, as it includes energy expended to maintain basic bodily functions while at rest.
  • Total Daily Energy Expenditure (TDEE): The total amount of calories burned in a day, including all physical activities. TDEE can be estimated using equations like the Harris-Benedict or Mifflin-St Jeor formulas. I provide an example in my post, How To Speed Up Your Basal Metabolic Rate.


Part 3: Metabolic Health and Dysfunction

metabolic syndrome indices

There are basically five factors that are evaluated to determine metabolic health or dysfunction. As I explain in Metabolically Unfit, the following are the indicators, along with acceptable measurements (ideal numbers in parentheses).

Acceptable and Preferable Metabolic Markers

Acceptable  Preferable
1. Systolic/diastolic blood pressure, mmHg <120 / <80 110/70
2. Fasting Glucose mg/dL and HbA1c mg/dL, % <100




3. Waist Circumference men/women, inches <40 / <37 <35 / 3.15
4. HDL-C men/women, inches 40 / 50 60 / 60
5. Triglycerides, mg/dL <150 <100
Impact of Metabolic Syndrome Factors

“Metabolic Syndrome” is defined by the prevalence of any three of the following symptoms (also covered in the above table) for these reasons:

  1. Waist Circumference: Excess abdominal fat is associated with increased inflammation and insulin resistance, both of which impair mitochondrial function and reduce biogenesis. (Read What Your Waist to Height Ratio Reveals About Your Health and How A Plant-based Diet Can Improve It.)
  2. HDL (High-Density Lipoprotein): Low HDL levels are linked to poor lipid metabolism and oxidative stress, hindering mitochondrial efficiency and ATP production .
  3. Blood Pressure: Hypertension can cause endothelial dysfunction and reduced blood flow, limiting nutrient and oxygen delivery to cells, thereby affecting mitochondrial health .
  4. Fasting Glucose: Elevated blood sugar levels can lead to glycation and oxidative damage, impairing mitochondrial function and biogenesis .
  5. Triglycerides: High levels of triglycerides contribute to fatty acid accumulation in tissues, leading to lipotoxicity and mitochondrial dysfunction.


Part 4: Assessing Mitochondrial Biogenesis

Recall that mitochondrial biogenesis is the process by which new mitochondria are formed within the cell, enhancing the cell’s capacity to produce ATP, which cells require to live.

How important is ATP?

Well, consider this: Without ATP, we couldn’t form a thought or move a muscle. ATP keeps our nerves firing and our heart beating. It’s our body’s “energy currency”.

If you produced no ATP, you’d be dead in about six seconds.

That’s unlikely to happen, but what will happen to a greater or lesser extent is that your capacity to produce ATP via mitochondrial biogenesis will decline as you age. Let’s first look at what constitutes adequate mitochondrial biogenesis and then its age-related decline.

Indicators of Adequate Mitochondrial Biogenesis
  • Physical Endurance and Recovery: Enhanced endurance and quicker recovery times often indicate healthy mitochondrial function. This is subjective and can vary given several unconstrained factors, such as exercise intensity and frequency; however, this indication is the most accessible.
  • Biomarkers: Levels of certain proteins (e.g., PGC-1α, a master regulator of mitochondrial biogenesis) can be measured through blood tests to assess mitochondrial health, although a provider for this test is difficult to find.
  • Muscle Biopsy: Direct measurement of mitochondrial density and function in muscle tissues, though this is invasive and less commonly used.


Part 5: Age-Related Decline in Mitochondrial Biogenesis


Causes of Decline with Age
  • Oxidative Stress: Accumulation of oxidative damage over time impairs mitochondrial DNA and function .
  • Decreased Physical Activity: Reduced activity levels with age lead to fewer signals for mitochondrial biogenesis .
  • Nutrient Deficiency: Aging can affect nutrient absorption, impacting the availability of key vitamins and minerals required for mitochondrial function.
Metabolism Decline

A decline in your metabolic rate is unlikely the reason for weight gain.

It’s common to think that your metabolism means metabolic rate (the speed at which your body burns calories to keep its basic functions running), that it slows with age, and is the reason your body composition changes, but that’s not usually the case. As you’re discovering here, metabolism is more than its “rate”, and although your metabolic rate does change during your early life, it plateaus between the ages of 20 and 60, and only decreases by around 1% per year after that.

Typically, the reason people tend to gain weight as they get older is due to less activity, being more sedentary and losing muscle tissue (sarcopenia). Consistent cardiorespiratory exercise and resistance training can dramatically reduce the decrease of your metabolic rate after 60 years of age.

Impact on Hallmarks of Aging

Mitochondrial dysfunction is itself one of the Hallmarks of Aging that I describe in The New Hallmarks of Aging — Why You Age, and it affects more of the other Hallmarks more than any other.

  • Genomic Instability: Mitochondrial dysfunction contributes to DNA damage.
  • Telomere Attrition: Poor mitochondrial function is linked to faster telomere shortening.
  • Loss of Proteostasis: Impaired mitochondria disrupt protein homeostasis, leading to accumulation of damaged proteins.
  • Deregulated Nutrient Sensing: Dysfunctional mitochondria affect cellular signaling pathways involved in nutrient sensing.


Part 6: Enhancing Mitochondrial Health

Metabolic and mitochondrial health are tied together — typically you don’t get one without the other.

How to Improve Mitochondrial Biogenesis and Function
  • Regular Physical Activity: Exercise stimulates mitochondrial biogenesis through increased demand for ATP and activation of pathways like AMPK and PGC-1α .
  • Balanced Diet: Consuming a diet rich in whole, unprocessed foods provides essential nutrients and antioxidants that support mitochondrial health. (See “Plant Foods” below and my posts The Blue Zone Diet Will Transform You and Eat Like A Gorilla.)
  • Intermittent Fasting: Fasting can promote mitochondrial biogenesis by activating autophagy and stress response pathways. (My posts about IF. Note: Recent studies affirm that the benefits from IF for the metabolically healthy mainly come from caloric restriction and closing your eating window two to three hours before bed.)
  • Adequate Sleep: Quality sleep is crucial for mitochondrial repair and biogenesis. (My posts about restorative sleep,)
  • Stress Management: Reducing chronic stress lowers cortisol levels, which can negatively impact mitochondrial function. (My posts about stress.)
Diet and Metabolism: The Impact of Plant Foods vs. Ultra-Processed Foods
  • Plant Foods: Greens, cruciferous vegetables, whole grains, fruits, seeds, and nuts are nutrient-dense, rich in fiber, antioxidants, vitamins, and minerals. They support metabolic health by reducing inflammation, improving insulin sensitivity, and promoting healthy mitochondrial function. (Read Move To A Plant-based Diet With These 2 Food Groups.)
  • Ultra-Processed Foods: These foods are typically high in refined sugars, unhealthy fats, and additives, leading to increased inflammation, oxidative stress, and insulin resistance. Such conditions impair mitochondrial function and biogenesis, reducing ATP production and cellular health. (Read How Ultraprocessed Foods Can Hurt Your Brain and Gut.)


Your Takeaway

So, now you know that there’s a strong link between diet, physical activity, and mitochondrial health that is crucial for maintaining a youthful metabolism and extending health span. Shape your lifestyle choices accordingly to enhance your mitochondrial function, improve energy levels, and reduce the risk of age-related diseases, including several Hallmarks of Aging.

It all distills down to these five things:

1. Eat more plant foods, such as greens, cruciferious veggies, legumes (beans and lentils), fruits, nuts (especially walnuts and almonds), seeds (pumpkin, hemp, chia and flax) and whole grains (buckwheat, barley, millet, quinoa, bulger, oats).

2. Eliminate ultra-processed foods.

Here’s a chart from Healthline to help you make some nutritious swaps:

Ultra-processed Processed Home version
sweetened breakfast cereals plain bran cereal oat groats or steel-cut oats sweetened with honey
soda artificially flavored sparkling water water with a splash of fruit juice or fruit slices
flavored potato chips plain tortilla chips DIY pita chips
white bread whole wheat bread with minimal ingredients homemade baked potato chips
fried chicken deli rotisserie chicken roast chicken from scratch
flavored candy bar with long ingredient list simple candy bar with short ingredient list dark chocolate squares
frozen, blended coffee drink store-bought cold brew drip coffee
mashed potato flakes frozen potatoes fresh, whole potatoes
energy drink sweetened fruit juice fresh-squeezed orange juice
flavored granola bars with added sugar and preservatives granola bars with minimal additives DIY granola
artificially flavored cheese crackers naturally flavored crackers apple and cheese slices

3. Regularly do cardiorespiratory exercises (fast walking, jogging, stairs, biking, rowing, swimming) and resistance training (weights and/or calisthenics).

4. Lower your stress by first identifying it and the second, lowering it through mindfulness and meditation.

5. Get restorative sleep on a regular basis.



  1. Medical News Today. (2020). Plant-based diet: Everything you need to know. Retrieved from
  2. Healthline. (2021). The health benefits of leafy greens. Retrieved from
  3. Harvard T.H. Chan School of Public Health. (n.d.). The nutrition source: Processed foods and health. Retrieved from
  4. Mayo Clinic. (2020). Nutrition and healthy eating: Ultra-processed foods. Retrieved from
  5. National Institutes of Health. (2014). Abdominal fat and what to do about it. Retrieved from
  6. Cleveland Clinic. (2020). HDL (Good), LDL (Bad) Cholesterol and Triglycerides. Retrieved from
  7. American Heart Association. (2021). High blood pressure and metabolic syndrome. Retrieved from
  8. Diabetes UK. (2021). High blood glucose (hyperglycaemia). Retrieved from
  9. WebMD. (2020). Triglycerides: What you need to know. Retrieved from
  10. NCBI. (2017). Aging and mitochondrial function. Retrieved from
  11. Scientific American. (2019). How exercise affects your mitochondria. Retrieved from
  12. Nature. (2015). Intermittent fasting promotes metabolic health. Retrieved from



Last Updated on June 22, 2024 by Joe Garma

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Joe Garma

I help people live with more vitality and strength. I'm a big believer in sustainability, and am a bit nutty about optimizing my diet, supplements, hormones and exercise. To get exclusive Updates, tips and be on your way to a stronger, more youthful body, join my weekly Newsletter. You can also find me on LinkedIn, Twitter and Instagram.

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