• Mitochondria = your body’s “motherboard.” Most chronic disease traces back, in part, to mitochondrial dysfunction—so protect the network that powers you.

• Cardio: Do both HIIT and MICT, but if you must choose one for mitochondrial health, pick HIIT (stronger systemic signal, lactylation → PGC-1α, best results per minute).

• Concurrent training: For mitochondria, go cardio first, then strength (70–80% 1RM), start lifting within ≤15 min.

• Sleep: Sleep lowers mitochondrial ROS, repairs the network, clears damaged organelles, and resets the “sleep-pressure” switch.

• Sunlight (670–900 nm): Short, daily skin exposure beats long, sporadic sessions.

  • Summer: 5–6 min midday; 10–15 min early/late.

  • Winter: 15–25 min at noon; up to 30 min early/late.
    Prioritize bare back/chest; add ~⅓ time with light clothes/clouds; adjust by skin tone. LEDs lack >660 nm and skew blue.

• SAMe: Keep it adequate. It fuels glutathione defenses, maintains mitochondrial membranes (phosphatidylcholine), stabilizes methylation, supports ETC, and prevents over-oxidation.

• Diet + fasting: Mediterranean-style, rich in polyphenols; regular short fasts; moderate protein; cyclical (not constant) ketosis (e.g., fasted aerobic work).

• Protein: 1.2–1.6 g/kg/day [≈0.54–0.73 g/lb/day]. More isn’t better—renal downsides without added benefit.

• Heat:

  • Sauna: 3–4 × 12–15 min at 80–90 °C [176–194 °F], 3–4-min breaks, 4–5 days/week.
    If that’s too much: 20 min at 80 °C [176 °F], 3–4×/week.

  • Hot bath: 45 °C [113 °F] for 45 min (water to base of neck). Hydrate (water + sodium).

• Cold: 10–12 °C [50–53.6 °F] water, 3 × 3 min with light movement between, 3–4×/week. After sauna = extra kick. If chasing hypertrophy, wait ~6 h post-lifting.

• Stress & breathing: Keep cortisol in check. Practice slow nasal diaphragmatic breathing (4–6 breaths/min, exhale ≥ inhale) 10–20 min/day, ≥4 days/week.

• Relationships: Positive social ties synchronize biology, reduce oxidative stress, and support mitochondrial health.

Bottom line: Give mitochondria the environment they evolved for—movement, sunlight, adequate SAMe, smart heat/cold, nutrient-dense food with brief fasts, enough protein and sleep, low stress, and real human connection. No drugs or fancy tech required.

(This article is for educational purposes only and does not constitute medical advice. Lithium can interact with medications and is not appropriate for everyone. Do not start, stop, or change any treatment without talking to your healthcare professional.)

***

If this helped you, collect this post on Paragraph to support my work. Thank you!

***

Now that we know how important it is to keep the “motherboard” finely tuned, it’s time to act. The following tools are simple, backed by recent science, and—best of all—can be woven into daily life without any “high-tech.”

Cardiorespiratory physical activity is, without a doubt, one of the best signals (energy demand) we can send the body to tell it to make more mitochondria and improve the quality of the ones we already have. First it stimulates them to work, and then it triggers an adaptive response that increases both their number and their efficiency.

When someone is so out of shape that they get winded climbing a few stairs and says, “I’m out of breath,” what they’re feeling isn’t a lack of air per se, but that their cardiovascular, respiratory, and muscular systems can’t deliver oxygen to cells—or turn what does arrive into energy—at the speed the effort requires (due, among other things, to low mitochondrial density).

To keep it very simple, we could say there are two main ways to train “cardio”:

1. Short high-intensity intervals (HIIT): more on the anaerobic side (with an “oxygen debt”).

2. Long-duration, moderate-intensity continuous cardio (MICT): more aerobic (with oxygen).

Both types of exercise induce different adaptations in the mitochondrial network (study):

· Short, intense bursts (HIIT): they create a more longitudinal network, with connections aligned along the muscle axis (think straight, fast highways). This speeds the flow of ATP right where the muscle generates force, enabling brief power peaks and quick recoveries.

· Continuous, moderate exercise (MICT): it yields a grid-like network, with both transverse and longitudinal connections (imagine crisscrossing streets and avenues). This allows ATP to be distributed evenly, favoring sustained efforts and resistance to fatigue.

Of course, you don’t have to pick just one. The ideal approach is to combine both, adapting them to each person’s level. However, if the sole goal were to improve mitochondrial health and I had to choose just one, I’d go with HIIT. Here’s why:

1. Full-body coordination

As we saw in the first part of the article, much of our physical and mental health depends on maintaining internal energy coherence: all mitochondria working in sync and energy flowing without bottlenecks.

High-intensity exercise boosts that coherence because it poses a bigger energy challenge to the body–mind. It forces total collaboration among organs, cells, and mitochondria. It’s not just about moving muscles faster; it’s a genuine storm of signals among the brain, heart, lungs, blood vessels—and, of course, the mitochondria.

2. Epigenetic signaling via lactylation and activation of the PGC-1α gene

As I explain in more detail in my book Nutritional Epigenetics, lactylation is a recently discovered epigenetic process.

Lactate is a metabolite generated when we use glucose as fuel. The body can also recycle it and use it in the mitochondria to produce energy, especially in the brain, muscles, and heart.

During high-intensity exercise, the high energy demand increases glucose use and, therefore, lactate production. When the mitochondria’s capacity to recycle it is exceeded, blood lactate builds up.

Here’s where lactylation comes in: it consists of adding a lactyl group (derived from lactate) to histones, the proteins around which DNA is wrapped. Normally, histones compact DNA, reducing access to certain genes. But when the lactyl group binds, that structure loosens and allows, among other effects, activation of the PGC-1α gene, which is responsible for creating new mitochondria.

In short: the rise in lactate from intense exercise is a powerful signal for the body to make more mitochondria and improve the efficiency of the ones it already has.

3. Greater efficiency per unit of time

Another advantage of HIIT is that it requires less time to achieve results equivalent to—or better than—traditional cardio.

According to 2025 studies and meta-analyses (study, study), high-intensity interval training generates roughly twice the mitochondrial adaptation per hour invested as low-intensity continuous work. In other words: more volume and higher quality in your cellular “power grid” per minute trained.

Strength training has numerous benefits, but if we’re speaking strictly about improving the quantity and quality of mitochondria, it’s much less efficient than cardio. This is because cardio activates the AMPK–PGC-1α pathway, which signals the body to make more mitochondria (biogenesis). In contrast, strength work activates a different pathway: mTOR, which is more involved in muscle growth (protein synthesis, hypertrophy).

That said, the evidence indicates that concurrent training (combining cardio and strength) not only does not interfere with mitochondrial biogenesis, but actually further enhances the signal activated by cardio alone (study).

If your priority is to optimize mitochondrial health (and not hypertrophy), there are three key factors to watch (study):

1. Moderate–high load and moderate repetitions
   High mechanical tension appears to be the trigger that turns the mTOR pathway into an ally of PGC-1α. In contrast, protocols with lots of repetitions and low load could weaken that effect.

2. Order matters: cardio first, then strength
   Doing cardio first depletes more ATP and activates AMPK–PGC-1α. The subsequent strength training (with loads between 70–80% of 1 RM) activates mTOR, further reinforcing the activation of PGC-1α.

3. Timing matters too
   Strength should be performed immediately after cardio (within ≤15 minutes), since this maximizes the synergistic cascade between mTOR and PGC-1α.

The answer to the mystery of why animals sleep may lie in mitochondria.

A revealing study from the University of Oxford, newly published (July 2025) in Nature, shows that the “pressure” to sleep arises from the buildup of electrical stress in the mitochondria of certain neurons.

As the day goes on, the mitochondria in these sleep-regulating neurons become overloaded and start to lose electrons. This generates harmful reactive oxygen species (ROS). When that “electron leak” crosses a threshold, it acts as a warning signal: the brain must sleep before the damage spreads.

Four coordinated processes occur during sleep:

1. Excess stored energy decreases
   During the day, these neurons barely work and accumulate energy (ATP). When we sleep, they activate and begin to spend that energy, eliminating the excess that caused the overload (and the production of ROS).

2. Mitochondria repair themselves and fuse again
   While we’re awake, mitochondria fragment. During sleep, they re-join and form networks. This improves their function and reduces electron loss.

3. The most damaged mitochondria are removed and repaired
   Sleep activates a cleaning system that recycles broken or more oxidized mitochondria, preventing them from continuing to generate reactive oxygen species.

4. New mitochondrial parts are made
   During the day, genes that code for new parts are activated. At night, those parts are assembled and mitochondria are renewed, improving their efficiency and reducing the risk of damage.

In short: these neurons act like automatic circuit breakers, activating the rest (sleep) system to prevent a ROS overload in mitochondria. Sleep restores ATP demand, reconfigures the mitochondrial network, and removes the most dysfunctional organelles. The danger signal subsides, and the sleep-pressure “switch” resets until the next wake period.

These findings also help explain why smaller animals—which consume more oxygen per gram of body weight (a faster metabolism)—tend to sleep more (they need to repair more damage) and live shorter lives.
Sleep, like aging, may be an inevitable consequence of how we generate energy. Another way to understand the phrase: “we die because we live.”

Mitochondria respond to light—but not just any light, rather the kind they evolved with: light spanning the full spectrum of wavelengths, including the longer ones (between 670 and 860 nanometers), i.e., sunlight.

Several recent studies have shown that direct exposure of our skin to long wavelengths, like those present in sunlight (with no window in between), penetrates deeply into our tissues. Unlike blue light, which remains in the skin, these wavelengths pass even through the chest or clothing, reaching internal tissues such as muscles, nerves, or the retina. And most importantly: once inside, they improve mitochondrial function.

A trial newly published in Nature (July 2025) showed that after exposing participants’ backs for 15 minutes to 850 nm infrared light (similar to sunlight), visual function, mitochondrial function, and ATP production improved 24 hours later—even when the eyes had been completely covered. How is this possible? Because the effect doesn’t depend solely on the eyes: the skin acts as a gateway, triggering effects that spread throughout the body.

Another 2024 study analyzed isolated mitochondria exposed to 810 nm light. The results were clear: the light increased energy (ATP) production, with a conversion efficiency above 10%. This is notable, especially considering that natural photosynthesis rarely exceeds 5%.

The most interesting finding was that reaching a “total dose” of light wasn’t enough. The cadence and power at which it was applied mattered as much or more than the total energy delivered. In other words, the quality and intensity of sunlight are key.

In another recent study, this time in healthy humans, a single 15-minute exposure to red light (670 nm) on the back was enough to significantly reduce blood glucose levels after consuming sugar (an oral glucose test). This reduction affected not only the peak but also the total area under the curve (AUC); in other words, there was less glucose circulating over time. This finding suggests that sunlight may benefit our metabolism, even in people without preexisting conditions.

In addition, some participants exhaled more carbon dioxide after exposure, indicating greater glucose oxidation. In other words, their mitochondria were making better use of the available fuel. And all of this without any drugs—just light.

These same studies warn about the harmful effects of continuous exposure to today’s LED lights. In standard LED lighting (whether warm or cool—this doesn’t matter), there are barely any wavelengths above 660 nm; instead, blue light around 450 nm dominates. It’s an unnatural spectrum, far from the sun’s full spectrum. This blue light (without the longer wavelengths) reduces the energy efficiency of our mitochondria (increasing fatigue), raises heart rate, and increases blood glucose levels.

It should go without saying, but to be clear: getting these mitochondrial and health benefits does not mean sunbathing until you burn. Let’s see how to reach the minimum effective dose.

The useful range (670 to 900 nm) shown in studies is present all day, but its energy density varies with solar elevation and the atmosphere. In summer at midday, power in that range can be 2–3 times higher than in winter. At sunrise or sunset, intensity drops to only 15–25% of noon.

These are the minimum minutes needed to “activate” the mitochondrial effect, depending on context:

• Summer: 5–6 min at midday hours; 10–15 min early or late.

• Winter: 15–25 min at noon; up to 30 min early or late.

• Prioritize a bare back or chest.

• With light clothing or on cloudy days, increase time by one third.

Depending on your skin tone, these minutes may double, but beyond that point extra mitochondrial gain is minimal and photoaging increases. Once you reach that point, cover up with clothing, find shade, or apply sunscreen.

Remember: brief but daily exposure clearly beats long, sporadic sessions.

Bonus tip: Combining this exposure with exercise creates a special synergy; you don’t just get two simultaneous benefits—here 1 + 1 = 3.

Final thoughts: The human body evolved under sunlight. Today we spend 90% of our time indoors under artificial lighting, with lights that lack the beneficial wavelengths (>660 nm) and are dominated by bluish tones (<450 nm), which can harm our mitochondria. Returning to regular natural sunlight exposure isn’t only about synthesizing vitamin D; it’s also a direct source of energy and health.

In this section we’ve covered the benefits of sunlight that penetrates the skin, but there are additional benefits (improved mood, prevention of mental illness, among others) when sunlight enters through the eyes.

I won’t go into the specific ways to increase our levels of S-adenosylmethionine (SAMe), because I cover them extensively in my book Nutritional Epigenetics. In the book I explain in depth how increasing SAMe—and therefore improving our methylation capacity—slows aging and reduces disease risk. This happens because SAMe improves three key drivers of aging: epigenetic alterations, genomic instability, and mitochondrial dysfunction.

Here I will focus exclusively on SAMe’s benefits for our mitochondria:

• Reinforces antioxidant defense: Mitochondria generate energy, but they also produce harmful reactive oxygen species (ROS). To neutralize them, they use glutathione, for which SAMe is an essential precursor. Without enough SAMe, our mitochondria lose protection against oxidative stress.

• Maintains healthy mitochondrial membranes: Mitochondrial membranes need phosphatidylcholine (made from SAMe) to maintain their fluidity and function. When SAMe is lacking, these membranes become rigid and hinder energy production. In addition, a fluid membrane allows better entry of glutathione, which is essential for protecting the mitochondrion (study).

• Improves communication between the mitochondrion and the endoplasmic reticulum: During fasting or exercise, mitochondria and the endoplasmic reticulum increase their interaction to share calcium and generate energy. SAMe regulates this interaction, preventing the stress from that crosstalk from becoming toxic (study).

• Regulates fat burning and energy production: Under energy stress, SAMe acts like a “brake” that controls excessive fat oxidation (β-oxidation), thereby preventing runaway production of reactive oxygen species. It is a key regulator that prevents mitochondria from overworking.

• Maintains the mitochondrial electrical potential: To generate energy (ATP), the mitochondrion needs to maintain a specific electrical charge (“mitochondrial potential”). Adequate SAMe levels sustain this charge, preventing the cell’s energy collapse.

• Takes part in the epigenetic regulation of mitochondrial genes: SAMe donates methyl groups that modify the activity of mitochondrial genes (DNA methylation). Around 30% of cellular SAMe is found in mitochondria, where it is transported across the membrane (

In my book Evolutionary Nutrition I broadly summarize the benefits of basing our nutrition on the foods we evolved with and of including brief, regular periods of total food restriction (intermittent fasting).

This way of eating, with an alternating pattern (eat–fast, eat–fast…), seems ideal for caring for our mitochondria. A systematic review published in 2022 by several universities concluded that the most effective dietary strategy to boost mitochondrial biogenesis and improve its efficiency includes:

• A Mediterranean-style pattern rich in polyphenols.

• Regular episodes of energy restriction or fasting.

• A moderate but sufficient amount of protein.

• Prudent, cyclical use of ketosis (for example, fasted aerobic exercise), avoiding continuous ketogenic diets, especially in people with heart disease.

According to a recent study from the University of Santiago de Compostela, fasting benefits humans because it promotes health, delays aging, and protects against obesity. But for the adaptive response to be optimal, it is crucial to ensure sufficient SAMe levels in the body. As noted earlier, SAMe protects against mitochondrial oxidative stress, prevents liver injury, and maintains the functional integrity of mitochondria—mainly because it is required to synthesize phosphatidylcholine and protect cell membranes.

In addition, low SAMe levels in the liver impair metabolic adaptation after a fasting period. This is because they reduce the ability to quickly switch off fat oxidation once we start eating again, producing what we call “metabolic inflexibility.

Nothing gets built in the human body without enough protein (“no bricks, no building”). According to recent studies, consuming between 1.2 and 1.6 g of protein per kilogram of body weight per day [≈0.54–0.73 g/lb/day] provides the best balance between mitochondrial stimulus, kidney health, and dietary sustainability (study, study).

That said, it’s not advisable to exceed this range, especially as we age. It has been shown that eating more protein than necessary produces an unfavorable renal response, lowering glomerular filtration rate without offering any additional benefit (study). As so often happens in biology: “less is bad, but more isn’t better.”

In addition, it has also been demonstrated (study) that carbohydrate periodization (greater restriction on days with more aerobic than anaerobic work) optimizes training adaptations, increasing the size, content, number, and activity of mitochondria. I explain the specific protocols, the best way to implement them, and the science behind them in depth in my book Evolutionary Nutrition for Athletes.

A Finnish sauna session raises core body temperature just enough to activate heat-shock proteins. These proteins improve the efficiency of existing mitochondria and send a signal that activates the PGC-1α gene, which is needed to build new mitochondria (study, study).

The most effective protocol studied consists of 3–4 rounds of 12–15 minutes at 80–90 °C [176–194 °F], with 3–4-minute breaks outside the sauna at an ambient temperature of 20–22 °C [68–71.6 °F] (no cold immersion). The recommended frequency is 4–5 days per week (study, study).

Although this protocol is the most beneficial for mitochondria, it’s also quite demanding. If you don’t have experience, it’s best to adapt gradually (fewer minutes and fewer rounds), increasing as your tolerance improves—just as you would with exercise.

Remember that “perfect shouldn’t be the enemy of good.” If lack of time or difficulty keeps you from the ideal protocol, doing less is still positive (fewer weekly sessions or fewer minutes per session). A 20-minute protocol at 80 °C [176 °F], 3–4 times per week (if more sessions are feasible, even better), has also shown durable mitochondrial effects. And if you want to further amplify the benefits of the heat session, you can finish with a cold session (see below).

In addition, recent studies have shown that sauna use brings benefits beyond the mitochondrial (perhaps derived from them): it reduces cardiovascular mortality risk, increases endurance in athletes, helps preserve muscle mass and strength, decreases inflammation, boosts our “brain fertilizer” (BDNF) supporting neurogenesis, reduces dementia risk, improves mood, and lowers anxiety.

It has also been shown that a hot bath at 45 °C [113 °F] for 45 minutes straight, with water up to the base of the neck, delivers mitochondrial benefits comparable to the best sauna protocol (study).

This is because hot water has two thermophysical advantages:

1. Higher conductivity: it transfers heat to the body more quickly.

2. It suppresses evaporation: you lose less heat through sweat.

Thus, for the same duration—but at a lower temperature—immersion produces an equivalent rise in body temperature and an even more intense adaptive response.

A clarification: typical hot tubs or gym spas won’t do. In most gyms the water is kept between 37–39 °C [98.6–102.2 °F] (for comfort and safety), a temperature insufficient to obtain these benefits.

Warning: Before doing any of these protocols, it is essential to ensure proper hydration (water + sodium).

Intermittent cold exposure is also a powerful activator for mitochondrial biogenesis and optimization. The rapid drop in temperature triggers a spike of norepinephrine, stimulating the AMPK/SIRT1 → PGC-1α pathway, and activates UCP-1, the protein responsible for heat production in brown fat. All of this increases the number of mitochondria, improves their coupling/uncoupling capacity, and promotes fat burning. In addition, the brief pulses of reactive oxygen species (ROS) generated by cold strengthen mitochondrial antioxidant defenses (study, study).

• Cold water at 10–12 °C [50–53.6 °F]

• 3 rounds of 3 minutes (9 minutes total)

• 2–3 minutes of easy movement (light drying) between rounds

• Do it 3–4 days per week

• Doing it after a sauna session enhances the benefits

If you’ve done strength training and your goal is hypertrophy, it’s better to wait about 6 hours before applying cold (or do it on rest days), since cold blunts the acute post-exercise inflammation needed to generate adaptations.

Exposure to stressful situations alters our neuroendocrine system, increasing the release of cortisol and catecholamines. This can generate mitochondrial dysfunction, an accumulation of damaged proteins, and an excess of reactive oxygen species (ROS). The result is oxidative stress, increased cell membrane permeability, DNA damage, and inflammatory reactions that lead to accelerated cellular aging and even cell death (study). No small thing.

In addition, the relationship between stress and mitochondria is bidirectional: stress harms our mitochondria, and dysfunctional mitochondria make us worse at handling stress, generating even more stress and damage—a vicious cycle.

On the other hand, it has been shown that stress-induced mitochondrial damage also exaggerates the immune response, contributing to depressive behavior (study) and other psychiatric illnesses (study). To grasp the relevance of mitochondria in our brain, it’s enough to know that a single neuron in the cerebral cortex consumes (at rest) around 4.7 billion molecules of ATP per second (yes, almost 5 million each second), and in the cortex alone (the outermost layer) we have about 12 million neurons.

Moreover, stress not only harms existing mitochondria; it also hinders the synthesis of new mitochondria (study).

It’s no surprise, then, that when we breathe in a way that favors relaxation, markers of oxidative stress go down, mitochondrial biogenesis switches on, and our bioenergetic capacity improves (study, study).

Although there is no “one protocol,” the scientific literature converges on a pattern that’s most effective: breathing that is deep and slow (4–6 breaths per minute), nasal, diaphragmatic (with abdominal expansion), and with an exhale as long as—or up to twice as long as—the inhale. These benefits only appear with regular, deliberate practice (10–20 minutes per day, ≥4 days per week).

Under chronic stress, men tend to cross the threshold into mitochondrial dysfunction more quickly. Women, by contrast, preserve mitochondrial function better under stress thanks to the protective effect of estradiol, which promotes the creation of new mitochondria, improves energy efficiency, and strengthens antioxidant defenses. After menopause, however, as estradiol declines, that protection is lost and mitochondria become as vulnerable as in men (study).

Positive social experiences—from a friendly conversation to a shared laugh—not only improve our mood; they also seem to fine-tune mitochondrial function. Although conclusive human studies are still lacking, numerous animal experiments have shown that enriched environments and social relationships promote mitochondrial biogenesis, increase efficiency, and reduce oxidative damage (study). This occurs because social interaction lowers cortisol, raises oxytocin, and activates molecular pathways that strengthen our cellular “energy network.”

In humans, early evidence points the same way. Recent studies have observed that positive emotions and social support are associated with greater mitochondrial activity, less network fragmentation, and fewer signs of biochemical stress. Hugs, music, laughter, or even shared exercise can act like metronomes that synchronize our cells and recharge our energy reserves. Caring for our bonds can literally be a way to care for our vitality, because mitochondria respond not only to what we eat or how we train, but also to how we live and with whom we share it.

Here too the relationship is bidirectional: the better our mitochondrial health, the more we enjoy psychosocial experiences and the better our mood (study).

Our systemic health and the pace at which we age depend to a great extent on the state of our mitochondria. The latest scientific evidence suggests there is no current chronic disease that isn’t linked, to some degree, to mitochondrial dysfunction.

Therefore, it’s essential to care for the ones that care for us, providing the stimuli and environment they’ve known for millions of years: physical exercise, adequate SAMe levels, sunlight exposure, a calm life with managed stress, sufficient high-quality protein and sleep, brief exposures to heat and cold, nutritious foods alternated with short fasting periods, and enriching social relationships (connection with your “tribe”).

Let’s get to it. No drugs or sophisticated technology are needed.

Get Nutritional Epigenetics on Amazon

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Get Evolutionary Nutrition for Athletes

***

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***

• Mitochondria = your body’s “motherboard.” Most chronic disease traces back, in part, to mitochondrial dysfunction—so protect the network that powers you.

• Cardio: Do both HIIT and MICT, but if you must choose one for mitochondrial health, pick HIIT (stronger systemic signal, lactylation → PGC-1α, best results per minute).

• Concurrent training: For mitochondria, go cardio first, then strength (70–80% 1RM), start lifting within ≤15 min.

• Sleep: Sleep lowers mitochondrial ROS, repairs the network, clears damaged organelles, and resets the “sleep-pressure” switch.

• Sunlight (670–900 nm): Short, daily skin exposure beats long, sporadic sessions.

  • Summer: 5–6 min midday; 10–15 min early/late.

  • Winter: 15–25 min at noon; up to 30 min early/late.
    Prioritize bare back/chest; add ~⅓ time with light clothes/clouds; adjust by skin tone. LEDs lack >660 nm and skew blue.

• SAMe: Keep it adequate. It fuels glutathione defenses, maintains mitochondrial membranes (phosphatidylcholine), stabilizes methylation, supports ETC, and prevents over-oxidation.

• Diet + fasting: Mediterranean-style, rich in polyphenols; regular short fasts; moderate protein; cyclical (not constant) ketosis (e.g., fasted aerobic work).

• Protein: 1.2–1.6 g/kg/day [≈0.54–0.73 g/lb/day]. More isn’t better—renal downsides without added benefit.

• Heat:

  • Sauna: 3–4 × 12–15 min at 80–90 °C [176–194 °F], 3–4-min breaks, 4–5 days/week.
    If that’s too much: 20 min at 80 °C [176 °F], 3–4×/week.

  • Hot bath: 45 °C [113 °F] for 45 min (water to base of neck). Hydrate (water + sodium).

• Cold: 10–12 °C [50–53.6 °F] water, 3 × 3 min with light movement between, 3–4×/week. After sauna = extra kick. If chasing hypertrophy, wait ~6 h post-lifting.

• Stress & breathing: Keep cortisol in check. Practice slow nasal diaphragmatic breathing (4–6 breaths/min, exhale ≥ inhale) 10–20 min/day, ≥4 days/week.

• Relationships: Positive social ties synchronize biology, reduce oxidative stress, and support mitochondrial health.

Bottom line: Give mitochondria the environment they evolved for—movement, sunlight, adequate SAMe, smart heat/cold, nutrient-dense food with brief fasts, enough protein and sleep, low stress, and real human connection. No drugs or fancy tech required.

(This article is for educational purposes only and does not constitute medical advice. Lithium can interact with medications and is not appropriate for everyone. Do not start, stop, or change any treatment without talking to your healthcare professional.)

***

If this helped you, collect this post on Paragraph to support my work. Thank you!

***

Now that we know how important it is to keep the “motherboard” finely tuned, it’s time to act. The following tools are simple, backed by recent science, and—best of all—can be woven into daily life without any “high-tech.”

Cardiorespiratory physical activity is, without a doubt, one of the best signals (energy demand) we can send the body to tell it to make more mitochondria and improve the quality of the ones we already have. First it stimulates them to work, and then it triggers an adaptive response that increases both their number and their efficiency.

When someone is so out of shape that they get winded climbing a few stairs and says, “I’m out of breath,” what they’re feeling isn’t a lack of air per se, but that their cardiovascular, respiratory, and muscular systems can’t deliver oxygen to cells—or turn what does arrive into energy—at the speed the effort requires (due, among other things, to low mitochondrial density).

To keep it very simple, we could say there are two main ways to train “cardio”:

1. Short high-intensity intervals (HIIT): more on the anaerobic side (with an “oxygen debt”).

2. Long-duration, moderate-intensity continuous cardio (MICT): more aerobic (with oxygen).

Both types of exercise induce different adaptations in the mitochondrial network (study):

· Short, intense bursts (HIIT): they create a more longitudinal network, with connections aligned along the muscle axis (think straight, fast highways). This speeds the flow of ATP right where the muscle generates force, enabling brief power peaks and quick recoveries.

· Continuous, moderate exercise (MICT): it yields a grid-like network, with both transverse and longitudinal connections (imagine crisscrossing streets and avenues). This allows ATP to be distributed evenly, favoring sustained efforts and resistance to fatigue.

Of course, you don’t have to pick just one. The ideal approach is to combine both, adapting them to each person’s level. However, if the sole goal were to improve mitochondrial health and I had to choose just one, I’d go with HIIT. Here’s why:

1. Full-body coordination

As we saw in the first part of the article, much of our physical and mental health depends on maintaining internal energy coherence: all mitochondria working in sync and energy flowing without bottlenecks.

High-intensity exercise boosts that coherence because it poses a bigger energy challenge to the body–mind. It forces total collaboration among organs, cells, and mitochondria. It’s not just about moving muscles faster; it’s a genuine storm of signals among the brain, heart, lungs, blood vessels—and, of course, the mitochondria.

2. Epigenetic signaling via lactylation and activation of the PGC-1α gene

As I explain in more detail in my book Nutritional Epigenetics, lactylation is a recently discovered epigenetic process.

Lactate is a metabolite generated when we use glucose as fuel. The body can also recycle it and use it in the mitochondria to produce energy, especially in the brain, muscles, and heart.

During high-intensity exercise, the high energy demand increases glucose use and, therefore, lactate production. When the mitochondria’s capacity to recycle it is exceeded, blood lactate builds up.

Here’s where lactylation comes in: it consists of adding a lactyl group (derived from lactate) to histones, the proteins around which DNA is wrapped. Normally, histones compact DNA, reducing access to certain genes. But when the lactyl group binds, that structure loosens and allows, among other effects, activation of the PGC-1α gene, which is responsible for creating new mitochondria.

In short: the rise in lactate from intense exercise is a powerful signal for the body to make more mitochondria and improve the efficiency of the ones it already has.

3. Greater efficiency per unit of time

Another advantage of HIIT is that it requires less time to achieve results equivalent to—or better than—traditional cardio.

According to 2025 studies and meta-analyses (study, study), high-intensity interval training generates roughly twice the mitochondrial adaptation per hour invested as low-intensity continuous work. In other words: more volume and higher quality in your cellular “power grid” per minute trained.

Strength training has numerous benefits, but if we’re speaking strictly about improving the quantity and quality of mitochondria, it’s much less efficient than cardio. This is because cardio activates the AMPK–PGC-1α pathway, which signals the body to make more mitochondria (biogenesis). In contrast, strength work activates a different pathway: mTOR, which is more involved in muscle growth (protein synthesis, hypertrophy).

That said, the evidence indicates that concurrent training (combining cardio and strength) not only does not interfere with mitochondrial biogenesis, but actually further enhances the signal activated by cardio alone (study).

If your priority is to optimize mitochondrial health (and not hypertrophy), there are three key factors to watch (study):

1. Moderate–high load and moderate repetitions
   High mechanical tension appears to be the trigger that turns the mTOR pathway into an ally of PGC-1α. In contrast, protocols with lots of repetitions and low load could weaken that effect.

2. Order matters: cardio first, then strength
   Doing cardio first depletes more ATP and activates AMPK–PGC-1α. The subsequent strength training (with loads between 70–80% of 1 RM) activates mTOR, further reinforcing the activation of PGC-1α.

3. Timing matters too
   Strength should be performed immediately after cardio (within ≤15 minutes), since this maximizes the synergistic cascade between mTOR and PGC-1α.

The answer to the mystery of why animals sleep may lie in mitochondria.

A revealing study from the University of Oxford, newly published (July 2025) in Nature, shows that the “pressure” to sleep arises from the buildup of electrical stress in the mitochondria of certain neurons.

As the day goes on, the mitochondria in these sleep-regulating neurons become overloaded and start to lose electrons. This generates harmful reactive oxygen species (ROS). When that “electron leak” crosses a threshold, it acts as a warning signal: the brain must sleep before the damage spreads.

Four coordinated processes occur during sleep:

1. Excess stored energy decreases
   During the day, these neurons barely work and accumulate energy (ATP). When we sleep, they activate and begin to spend that energy, eliminating the excess that caused the overload (and the production of ROS).

2. Mitochondria repair themselves and fuse again
   While we’re awake, mitochondria fragment. During sleep, they re-join and form networks. This improves their function and reduces electron loss.

3. The most damaged mitochondria are removed and repaired
   Sleep activates a cleaning system that recycles broken or more oxidized mitochondria, preventing them from continuing to generate reactive oxygen species.

4. New mitochondrial parts are made
   During the day, genes that code for new parts are activated. At night, those parts are assembled and mitochondria are renewed, improving their efficiency and reducing the risk of damage.

In short: these neurons act like automatic circuit breakers, activating the rest (sleep) system to prevent a ROS overload in mitochondria. Sleep restores ATP demand, reconfigures the mitochondrial network, and removes the most dysfunctional organelles. The danger signal subsides, and the sleep-pressure “switch” resets until the next wake period.

These findings also help explain why smaller animals—which consume more oxygen per gram of body weight (a faster metabolism)—tend to sleep more (they need to repair more damage) and live shorter lives.
Sleep, like aging, may be an inevitable consequence of how we generate energy. Another way to understand the phrase: “we die because we live.”

Mitochondria respond to light—but not just any light, rather the kind they evolved with: light spanning the full spectrum of wavelengths, including the longer ones (between 670 and 860 nanometers), i.e., sunlight.

Several recent studies have shown that direct exposure of our skin to long wavelengths, like those present in sunlight (with no window in between), penetrates deeply into our tissues. Unlike blue light, which remains in the skin, these wavelengths pass even through the chest or clothing, reaching internal tissues such as muscles, nerves, or the retina. And most importantly: once inside, they improve mitochondrial function.

A trial newly published in Nature (July 2025) showed that after exposing participants’ backs for 15 minutes to 850 nm infrared light (similar to sunlight), visual function, mitochondrial function, and ATP production improved 24 hours later—even when the eyes had been completely covered. How is this possible? Because the effect doesn’t depend solely on the eyes: the skin acts as a gateway, triggering effects that spread throughout the body.

Another 2024 study analyzed isolated mitochondria exposed to 810 nm light. The results were clear: the light increased energy (ATP) production, with a conversion efficiency above 10%. This is notable, especially considering that natural photosynthesis rarely exceeds 5%.

The most interesting finding was that reaching a “total dose” of light wasn’t enough. The cadence and power at which it was applied mattered as much or more than the total energy delivered. In other words, the quality and intensity of sunlight are key.

In another recent study, this time in healthy humans, a single 15-minute exposure to red light (670 nm) on the back was enough to significantly reduce blood glucose levels after consuming sugar (an oral glucose test). This reduction affected not only the peak but also the total area under the curve (AUC); in other words, there was less glucose circulating over time. This finding suggests that sunlight may benefit our metabolism, even in people without preexisting conditions.

In addition, some participants exhaled more carbon dioxide after exposure, indicating greater glucose oxidation. In other words, their mitochondria were making better use of the available fuel. And all of this without any drugs—just light.

These same studies warn about the harmful effects of continuous exposure to today’s LED lights. In standard LED lighting (whether warm or cool—this doesn’t matter), there are barely any wavelengths above 660 nm; instead, blue light around 450 nm dominates. It’s an unnatural spectrum, far from the sun’s full spectrum. This blue light (without the longer wavelengths) reduces the energy efficiency of our mitochondria (increasing fatigue), raises heart rate, and increases blood glucose levels.

It should go without saying, but to be clear: getting these mitochondrial and health benefits does not mean sunbathing until you burn. Let’s see how to reach the minimum effective dose.

The useful range (670 to 900 nm) shown in studies is present all day, but its energy density varies with solar elevation and the atmosphere. In summer at midday, power in that range can be 2–3 times higher than in winter. At sunrise or sunset, intensity drops to only 15–25% of noon.

These are the minimum minutes needed to “activate” the mitochondrial effect, depending on context:

• Summer: 5–6 min at midday hours; 10–15 min early or late.

• Winter: 15–25 min at noon; up to 30 min early or late.

• Prioritize a bare back or chest.

• With light clothing or on cloudy days, increase time by one third.

Depending on your skin tone, these minutes may double, but beyond that point extra mitochondrial gain is minimal and photoaging increases. Once you reach that point, cover up with clothing, find shade, or apply sunscreen.

Remember: brief but daily exposure clearly beats long, sporadic sessions.

Bonus tip: Combining this exposure with exercise creates a special synergy; you don’t just get two simultaneous benefits—here 1 + 1 = 3.

Final thoughts: The human body evolved under sunlight. Today we spend 90% of our time indoors under artificial lighting, with lights that lack the beneficial wavelengths (>660 nm) and are dominated by bluish tones (<450 nm), which can harm our mitochondria. Returning to regular natural sunlight exposure isn’t only about synthesizing vitamin D; it’s also a direct source of energy and health.

In this section we’ve covered the benefits of sunlight that penetrates the skin, but there are additional benefits (improved mood, prevention of mental illness, among others) when sunlight enters through the eyes.

I won’t go into the specific ways to increase our levels of S-adenosylmethionine (SAMe), because I cover them extensively in my book Nutritional Epigenetics. In the book I explain in depth how increasing SAMe—and therefore improving our methylation capacity—slows aging and reduces disease risk. This happens because SAMe improves three key drivers of aging: epigenetic alterations, genomic instability, and mitochondrial dysfunction.

Here I will focus exclusively on SAMe’s benefits for our mitochondria:

• Reinforces antioxidant defense: Mitochondria generate energy, but they also produce harmful reactive oxygen species (ROS). To neutralize them, they use glutathione, for which SAMe is an essential precursor. Without enough SAMe, our mitochondria lose protection against oxidative stress.

• Maintains healthy mitochondrial membranes: Mitochondrial membranes need phosphatidylcholine (made from SAMe) to maintain their fluidity and function. When SAMe is lacking, these membranes become rigid and hinder energy production. In addition, a fluid membrane allows better entry of glutathione, which is essential for protecting the mitochondrion (study).

• Improves communication between the mitochondrion and the endoplasmic reticulum: During fasting or exercise, mitochondria and the endoplasmic reticulum increase their interaction to share calcium and generate energy. SAMe regulates this interaction, preventing the stress from that crosstalk from becoming toxic (study).

• Regulates fat burning and energy production: Under energy stress, SAMe acts like a “brake” that controls excessive fat oxidation (β-oxidation), thereby preventing runaway production of reactive oxygen species. It is a key regulator that prevents mitochondria from overworking.

• Maintains the mitochondrial electrical potential: To generate energy (ATP), the mitochondrion needs to maintain a specific electrical charge (“mitochondrial potential”). Adequate SAMe levels sustain this charge, preventing the cell’s energy collapse.

• Takes part in the epigenetic regulation of mitochondrial genes: SAMe donates methyl groups that modify the activity of mitochondrial genes (DNA methylation). Around 30% of cellular SAMe is found in mitochondria, where it is transported across the membrane (

In my book Evolutionary Nutrition I broadly summarize the benefits of basing our nutrition on the foods we evolved with and of including brief, regular periods of total food restriction (intermittent fasting).

This way of eating, with an alternating pattern (eat–fast, eat–fast…), seems ideal for caring for our mitochondria. A systematic review published in 2022 by several universities concluded that the most effective dietary strategy to boost mitochondrial biogenesis and improve its efficiency includes:

• A Mediterranean-style pattern rich in polyphenols.

• Regular episodes of energy restriction or fasting.

• A moderate but sufficient amount of protein.

• Prudent, cyclical use of ketosis (for example, fasted aerobic exercise), avoiding continuous ketogenic diets, especially in people with heart disease.

According to a recent study from the University of Santiago de Compostela, fasting benefits humans because it promotes health, delays aging, and protects against obesity. But for the adaptive response to be optimal, it is crucial to ensure sufficient SAMe levels in the body. As noted earlier, SAMe protects against mitochondrial oxidative stress, prevents liver injury, and maintains the functional integrity of mitochondria—mainly because it is required to synthesize phosphatidylcholine and protect cell membranes.

In addition, low SAMe levels in the liver impair metabolic adaptation after a fasting period. This is because they reduce the ability to quickly switch off fat oxidation once we start eating again, producing what we call “metabolic inflexibility.

Nothing gets built in the human body without enough protein (“no bricks, no building”). According to recent studies, consuming between 1.2 and 1.6 g of protein per kilogram of body weight per day [≈0.54–0.73 g/lb/day] provides the best balance between mitochondrial stimulus, kidney health, and dietary sustainability (study, study).

That said, it’s not advisable to exceed this range, especially as we age. It has been shown that eating more protein than necessary produces an unfavorable renal response, lowering glomerular filtration rate without offering any additional benefit (study). As so often happens in biology: “less is bad, but more isn’t better.”

In addition, it has also been demonstrated (study) that carbohydrate periodization (greater restriction on days with more aerobic than anaerobic work) optimizes training adaptations, increasing the size, content, number, and activity of mitochondria. I explain the specific protocols, the best way to implement them, and the science behind them in depth in my book Evolutionary Nutrition for Athletes.

A Finnish sauna session raises core body temperature just enough to activate heat-shock proteins. These proteins improve the efficiency of existing mitochondria and send a signal that activates the PGC-1α gene, which is needed to build new mitochondria (study, study).

The most effective protocol studied consists of 3–4 rounds of 12–15 minutes at 80–90 °C [176–194 °F], with 3–4-minute breaks outside the sauna at an ambient temperature of 20–22 °C [68–71.6 °F] (no cold immersion). The recommended frequency is 4–5 days per week (study, study).

Although this protocol is the most beneficial for mitochondria, it’s also quite demanding. If you don’t have experience, it’s best to adapt gradually (fewer minutes and fewer rounds), increasing as your tolerance improves—just as you would with exercise.

Remember that “perfect shouldn’t be the enemy of good.” If lack of time or difficulty keeps you from the ideal protocol, doing less is still positive (fewer weekly sessions or fewer minutes per session). A 20-minute protocol at 80 °C [176 °F], 3–4 times per week (if more sessions are feasible, even better), has also shown durable mitochondrial effects. And if you want to further amplify the benefits of the heat session, you can finish with a cold session (see below).

In addition, recent studies have shown that sauna use brings benefits beyond the mitochondrial (perhaps derived from them): it reduces cardiovascular mortality risk, increases endurance in athletes, helps preserve muscle mass and strength, decreases inflammation, boosts our “brain fertilizer” (BDNF) supporting neurogenesis, reduces dementia risk, improves mood, and lowers anxiety.

It has also been shown that a hot bath at 45 °C [113 °F] for 45 minutes straight, with water up to the base of the neck, delivers mitochondrial benefits comparable to the best sauna protocol (study).

This is because hot water has two thermophysical advantages:

1. Higher conductivity: it transfers heat to the body more quickly.

2. It suppresses evaporation: you lose less heat through sweat.

Thus, for the same duration—but at a lower temperature—immersion produces an equivalent rise in body temperature and an even more intense adaptive response.

A clarification: typical hot tubs or gym spas won’t do. In most gyms the water is kept between 37–39 °C [98.6–102.2 °F] (for comfort and safety), a temperature insufficient to obtain these benefits.

Warning: Before doing any of these protocols, it is essential to ensure proper hydration (water + sodium).

Intermittent cold exposure is also a powerful activator for mitochondrial biogenesis and optimization. The rapid drop in temperature triggers a spike of norepinephrine, stimulating the AMPK/SIRT1 → PGC-1α pathway, and activates UCP-1, the protein responsible for heat production in brown fat. All of this increases the number of mitochondria, improves their coupling/uncoupling capacity, and promotes fat burning. In addition, the brief pulses of reactive oxygen species (ROS) generated by cold strengthen mitochondrial antioxidant defenses (study, study).

• Cold water at 10–12 °C [50–53.6 °F]

• 3 rounds of 3 minutes (9 minutes total)

• 2–3 minutes of easy movement (light drying) between rounds

• Do it 3–4 days per week

• Doing it after a sauna session enhances the benefits

If you’ve done strength training and your goal is hypertrophy, it’s better to wait about 6 hours before applying cold (or do it on rest days), since cold blunts the acute post-exercise inflammation needed to generate adaptations.

Exposure to stressful situations alters our neuroendocrine system, increasing the release of cortisol and catecholamines. This can generate mitochondrial dysfunction, an accumulation of damaged proteins, and an excess of reactive oxygen species (ROS). The result is oxidative stress, increased cell membrane permeability, DNA damage, and inflammatory reactions that lead to accelerated cellular aging and even cell death (study). No small thing.

In addition, the relationship between stress and mitochondria is bidirectional: stress harms our mitochondria, and dysfunctional mitochondria make us worse at handling stress, generating even more stress and damage—a vicious cycle.

On the other hand, it has been shown that stress-induced mitochondrial damage also exaggerates the immune response, contributing to depressive behavior (study) and other psychiatric illnesses (study). To grasp the relevance of mitochondria in our brain, it’s enough to know that a single neuron in the cerebral cortex consumes (at rest) around 4.7 billion molecules of ATP per second (yes, almost 5 million each second), and in the cortex alone (the outermost layer) we have about 12 million neurons.

Moreover, stress not only harms existing mitochondria; it also hinders the synthesis of new mitochondria (study).

It’s no surprise, then, that when we breathe in a way that favors relaxation, markers of oxidative stress go down, mitochondrial biogenesis switches on, and our bioenergetic capacity improves (study, study).

Although there is no “one protocol,” the scientific literature converges on a pattern that’s most effective: breathing that is deep and slow (4–6 breaths per minute), nasal, diaphragmatic (with abdominal expansion), and with an exhale as long as—or up to twice as long as—the inhale. These benefits only appear with regular, deliberate practice (10–20 minutes per day, ≥4 days per week).

Under chronic stress, men tend to cross the threshold into mitochondrial dysfunction more quickly. Women, by contrast, preserve mitochondrial function better under stress thanks to the protective effect of estradiol, which promotes the creation of new mitochondria, improves energy efficiency, and strengthens antioxidant defenses. After menopause, however, as estradiol declines, that protection is lost and mitochondria become as vulnerable as in men (study).

Positive social experiences—from a friendly conversation to a shared laugh—not only improve our mood; they also seem to fine-tune mitochondrial function. Although conclusive human studies are still lacking, numerous animal experiments have shown that enriched environments and social relationships promote mitochondrial biogenesis, increase efficiency, and reduce oxidative damage (study). This occurs because social interaction lowers cortisol, raises oxytocin, and activates molecular pathways that strengthen our cellular “energy network.”

In humans, early evidence points the same way. Recent studies have observed that positive emotions and social support are associated with greater mitochondrial activity, less network fragmentation, and fewer signs of biochemical stress. Hugs, music, laughter, or even shared exercise can act like metronomes that synchronize our cells and recharge our energy reserves. Caring for our bonds can literally be a way to care for our vitality, because mitochondria respond not only to what we eat or how we train, but also to how we live and with whom we share it.

Here too the relationship is bidirectional: the better our mitochondrial health, the more we enjoy psychosocial experiences and the better our mood (study).

Our systemic health and the pace at which we age depend to a great extent on the state of our mitochondria. The latest scientific evidence suggests there is no current chronic disease that isn’t linked, to some degree, to mitochondrial dysfunction.

Therefore, it’s essential to care for the ones that care for us, providing the stimuli and environment they’ve known for millions of years: physical exercise, adequate SAMe levels, sunlight exposure, a calm life with managed stress, sufficient high-quality protein and sleep, brief exposures to heat and cold, nutritious foods alternated with short fasting periods, and enriching social relationships (connection with your “tribe”).

Let’s get to it. No drugs or sophisticated technology are needed.

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