Optimize Mitochondrial Biogenesis To Extend Healthspan

Mitochondrial Biogenesis

Mitochondrial Biogenesis optimization will help you to live a long and strong life. If you want to extend your healthspan, learn what to do to enhance mitochondrial biogenesis.


Mitochondrial Biogenesis

Credit: genome.gov


Mitochondrial biogenesis is something worth knowing about if your aim is to live as healthy as you can for as long as you can. This is a story of sorts that involves three actors:

  1. Metabolism,
  2. ATP, and
  3. Mitochondria.

Understanding the intricate relationship between metabolism, ATP production, and mitochondrial function is crucial for optimizing health and extending health span.

High-quality plant foods and a healthy lifestyle promote efficient metabolism and robust mitochondrial biogenesis, while ultra-processed foods and industrially raised meat products can lead to metabolic disorders and mitochondrial dysfunction.

By focusing on nutrient-dense, antioxidant-rich foods and healthy lifestyle practices, we can support mitochondrial health, enhance energy production, and improve our healthspan — our healthy years.

Here’s what I cover in this post:

Let’s dig in…


How Metabolism, ATP, and Mitochondria Are Linked

ATP, generated by mitochondria, fuels metabolic processes, making mitochondria critical for sustaining metabolic functions. Mitochondria have their own DNA and are essential for cellular respiration, energy production, and regulating cellular metabolism. Without sufficient ATP, cells cannot perform essential functions, leading to impaired organ function and overall health decline. Mitochondria, by producing ATP, sustain cellular energy and play a key role in maintaining cellular health and function.

Mitochondria and metabolism are central to cellular energy production. Mitochondria convert nutrients from food into ATP through the citric acid cycle and oxidative phosphorylation. Metabolic processes provide the necessary substrates for ATP production. Efficient metabolism and mitochondrial function are crucial for maintaining cellular energy balance and overall health.


Metabolism encompasses all the chemical reactions that occur within a living organism to maintain life. It refers to the complex network of chemical reactions within living organisms that sustain life. These processes enable organisms to grow, reproduce, repair damage, and respond to their environment. Metabolism can be broadly divided into two categories:

  • Catabolism, which breaks down molecules to produce energy.
  • Anabolism, which uses energy to construct components of cells such as proteins and nucleic acids.

Recent research indicates that metabolic rate doesn’t necessarily slow down with age independently, but rather due to reduced physical activity and loss of lean body mass (muscle) [1]. Here’s how these factors interact with mitochondrial biogenesis:

  1. Reduced Activity Level:
    • Physical inactivity decreases the demand for ATP, leading to reduced mitochondrial biogenesis and function.
    • Regular physical activity stimulates mitochondrial biogenesis through pathways such as AMPK and PGC-1α, maintaining metabolic efficiency [2].
  2. Loss of Lean Body Tissue:
    • Muscle tissue is metabolically active and rich in mitochondria. A decline in muscle mass results in fewer mitochondria and reduced metabolic rate.
    • Strength training and resistance exercises can help preserve and build muscle mass, enhancing mitochondrial density and metabolic rate [3].


ATP (Adenosine Triphosphate) is known as the “energy currency” of the cell. It is a high-energy molecule that stores and supplies the energy needed for many biochemical cellular processes. ATP is crucial for activities such as muscle contraction, nerve impulse propagation, and chemical synthesis.


Mitochondria are the “powerhouses” of the cell, responsible for generating the majority of the cell’s supply of ATP through a process called oxidative phosphorylation. They are central to metabolism as they are the primary sites for oxidative phosphorylation, where the majority of ATP is produced.

Connecting the Three

ATP, generated by mitochondria, fuels metabolic processes, making mitochondria critical for sustaining metabolic functions. Mitochondria have their own DNA and are essential for cellular respiration, energy production, and regulating cellular metabolism.

Without sufficient ATP, cells cannot perform essential functions, leading to impaired organ function and overall health decline. Mitochondria, by producing ATP, sustain cellular energy and play a key role in maintaining cellular health and function.

Mitochondria and Metabolism play a central role in cellular energy production. Mitochondria are the site of the citric acid cycle (Krebs cycle) and oxidative phosphorylation. This is where nutrients from food are converted into ATP. Metabolic processes provide the substrates (e.g., glucose, fatty acids, amino acids) that mitochondria use to generate ATP. Thus, efficient metabolism and mitochondrial function are crucial for maintaining cellular energy balance and overall health.


The Goal: Optimize Mitochondrial Biogenesis

Mitochondrial biogenesis

Mitochondrial biogenesis is the process by which new mitochondria are formed within the cell. This is crucial for maintaining cellular energy levels, especially in high-energy-demand tissues such as muscles, brain, and heart.

Exercise, Muscle and Food

Optimizing mitochondrial biogenesis ensures efficient ATP production, reduces oxidative stress, and supports overall metabolic health. Enhanced mitochondrial function can improve physical endurance, cognitive function, and longevity [4].

Maintaining a high level of physical activity and muscle mass through exercise is critical for promoting mitochondrial biogenesis. Both aerobic exercise and resistance training stimulate pathways that enhance mitochondrial function and biogenesis:

  • AMPK Pathway Activation: Exercise activates AMPK (a fuel-sensing enzyme), which promotes the expression of PGC-1α, a master regulator of mitochondrial biogenesis [5]. 
  • Increased Muscle Mass: Resistance training increases muscle mass, which is directly related to higher mitochondrial content and improved metabolic health [6].

What you eat also greatly impacts your ability to form new mitochondria, which I’ll address in a moment, but first let me briefly explain how aging affects mitochondrial biogenesis.

Aging and Mitochondrial Biogenesis

As we age, the efficiency of mitochondrial biogenesis decreases. This decline is associated with reduced cellular energy production and increased susceptibility to oxidative damage.

Mitochondrial dysfunction is a recognized Hallmark of Aging. It’s linked to other hallmarks, such as genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, and cellular senescence, dysregulated nutrient sensing and altered intercellular communication.

(Read my post, The New Hallmarks of Aging: Why You Age.)

As we age, mitochondrial biogenesis (again, the process by which cells create new mitochondria) tends to decline. This decline contributes to several of the negative effects associated with aging.

Here’s a breakdown:

  • Reduced Mitochondrial Number: Studies have shown a decrease in the number and density of mitochondria within cells, especially in tissues with high energy demands like muscles and the brain [7].
  • Impaired Mitochondrial Function: Fewer mitochondria means less energy production and a decrease in cellular efficiency. Additionally, damaged mitochondria can accumulate, leading to increased production of harmful free radicals that further impair cellular function [8].

Why Optimizing Mitochondrial Biogenesis is Important in Aging:

  • Combating Cellular Decline: By promoting the creation of new, healthy mitochondria, we can potentially counteract the age-related decline in cellular energy production and function. This could contribute to improved physical performance, cognitive function, and overall health.
  • Reducing Oxidative Stress: Newer mitochondria tend to be more efficient and produce fewer free radicals. This helps to reduce oxidative stress, a major contributor to aging and age-related diseases [9].
  • Enhanced Cellular Repair Mechanisms: Mitochondria play a role in cellular repair processes. Optimizing their function could potentially improve the ability of cells to repair damage and maintain healthy function.

Optimizing mitochondrial biogenesis as get older holds promise for promoting healthy cellular function, reducing age-related decline, and potentially improving overall health and well-being.

Sounds like something worth pursuing,

Now let’s address why food matters.


The Journey of Food: From Digestion to Metabolism to ATP and Mitochondria


Food digestion to ATP

Metabolism, ATP and mitochondria depend on food, and the quality of food matters tremendously.

Here’s how the process works:

A. Digestion and Absorption

  1. Carbohydrates:
    • Broken down into simple sugars like glucose.
    • Absorbed into the bloodstream via the intestines.
  2. Proteins:
    • Broken down into amino acids.
    • Absorbed and used for protein synthesis or energy production.
  3. Fats:
    • Broken down into fatty acids and glycerol. (Fatty acids are the building blocks of the fat in our bodies and in the food we eat. , and glycerol is a naturally occurring alcohol.)
    • Absorbed and transported via the lymphatic system to the bloodstream.

The rest of this is sciency and complicated, but for those interested…

B. Cellular Uptake and Initial Metabolism

  1. Glucose:
    • Taken up by cells through glucose transporters.
    • In the cytoplasm (inside the membrane of cells), glucose undergoes glycolysis (the breakdown of glucose by enzymes) producing pyruvate, NADH, and a small amount of ATP (2 ATP per glucose molecule).
  2. Fatty Acids:
  3. Amino Acids:
    • Deaminated to remove the amino group (which is what “deaminated” means).
    • Converted into intermediates that enter the citric acid cycle.

C. Mitochondrial ATP Production:

  1. Citric Acid Cycle (Krebs Cycle):
    • Occurs in the mitochondrial matrix.
    • Pyruvate (from glycolysis) and acetyl-CoA (from beta-oxidation and amino acids) are further broken down.
    • Produces NADH, FADH2, and a small amount of ATP (2 ATP per glucose molecule).
  2. Oxidative Phosphorylation:
    • NADH and FADH2 donate electrons to the electron transport chain (ETC) in the inner mitochondrial membrane.
    • This process creates a proton gradient across the membrane.
    • The flow of protons back into the mitochondrial matrix through ATP synthase drives the production of a large amount of ATP (approximately 34 ATP per glucose molecule).

The bottom line: The food you eat supplies the basic energy source that is used to fuel your cells after it is broken down and converted into ATP.

The type of food you eat matters a great deal.


Impact of Ultra-Processed Foods and Industrially Raised Meat Products on Mitochondria and Metabolism

processed food types

Ultra-processed foods and industrially raised meat products negatively impact metabolism, ATP production, and mitochondrial biogenesis through several mechanisms:

  1. High Glycemic Carbs:
    • Lead to insulin resistance and hyperglycemia.
    • Causes oxidative stress and inflammation that damage mitochondria.
  2. Unhealthy Fats:
    • Saturated and trans fats disrupt mitochondrial membrane integrity and impair the electron transport chain (ETC).
    • Increase chronic inflammation, further damaging mitochondria.
  3. Low Nutrient Density:
    • Lack of essential nutrients and antioxidants.
    • Increases oxidative stress, leading to mitochondrial dysfunction.

Metabolic Disorders:

  • High LDL Cholesterol: Leads to atherosclerosis and endothelial dysfunction, increasing oxidative stress and damaging mitochondria .
  • High Blood Sugar (Hyperglycemia): Causes glycation of mitochondrial proteins, impairing their function .
  • High Triglycerides: Leads to lipid overload and lipotoxicity, damaging mitochondrial membranes and reducing ATP production.

(Read my post, Metabolic Syndrome Affects 30% of the U.S. Population — How About You?)

Remember — the objective is to enhance metabolism and mitochondrial biogenesis, and that is done by consuming the right foods, as well as specific lifestyle factors.


Optimizing Metabolism and Mitochondrial Biogenesis Through Diet and Lifestyle

Better mitochondria via diet and exercise

There are several arguments and pieces of evidence suggesting that plant-based foods can support mitochondrial biogenesis and overall mitochondrial health more effectively than animal-based foods.

Let’s run through these.

Dietary Choices

High-Quality Plant Foods:

Greens, Legumes, Cruciferous Vegetables, Grains, Seeds, and Nuts are rich in essential nutrients, antioxidants, and healthy fats. Such foods support mitochondrial function and biogenesis through activation of AMPK, SIRT1, and PGC-1α pathways.

  1. Healthy Fats:
    • Omega-3 fatty acids found in avocado, flaxseeds, chia seeds, hemp seeds and walnuts.
    • Enhance mitochondrial membrane fluidity and function.
  2. Low Glycemic Index Carbs:
    • These are carbohydrates that tend not to spike blood sugar [10].
    • Provide steady glucose release, preventing blood sugar spikes and insulin resistance.

Lifestyle Factors

  1. Regular Exercise:
    • Promotes mitochondrial biogenesis and function.
    • Increases insulin sensitivity and reduces oxidative stress.
  2. Intermittent Fasting:
    • Activates autophagy, promoting cellular repair and mitochondrial health.
    • Enhances mitochondrial biogenesis through activation of AMPK and SIRT1.
  3. Adequate Sleep:
    • Supports overall metabolic health.
    • Allows for cellular repair and reduces oxidative stress.

(See my posts on Exercise, Intermittent Fasting and Sleep)


Your Takeaway

There’s a lot more to be said about the connection between metabolism, ATP and mitochondria, and how the right foods and lifestyle factors contribute to optimizing metabolic biogenesis, which is particularly important as we age.

But for now, remember these four things:

  1. The food you eat eventually gets transformed into an energy source usable to power your cells, ATP.
  2. The quality of the food matters for the health of your metabolism, mitochondria and ATP.
  3. Mitochondrial biogenesis is about growing new, healthy mitochondria. Aging, ultra processed foods and industrially-grown animal products degrades mitochondrial health.
  4. Plant foods, such as legumes (beans and lentils), greens, cruciferous veggies, grains, nuts, seeds and fruits — along with consistent exercise — keeps your mitochondria healthy.


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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