Fuel for thought

A brain fit for the 21st century is one that understands – and respects – its own bioenergetic foundations

by Hannah Critchlow + BIO

A coloured transmission electron micrograph of a steroid-secreting cell of the zona fasciculata. The mitochondria (red) are surrounded by smooth endoplasmic reticulum (blue). Photo by Jose Calvo/Science Photo Library

is a neuroscientist, author and broadcaster based at Magdalene College at the University of Cambridge, UK. Her books include The Science of Fate (2019), Joined-Up Thinking (2022) and The 21st Century Brain (2026).

Edited byNigel Warburton

About 2 billion years ago, evolution performed an improbable experiment. A larger ancestral cell engulfed a smaller bacterium. It should have been a meal. Instead, it became a merger. The bacterium survived inside its host, and together they forged one of the most consequential partnerships in the history of life. The host offered shelter and access to oxygen. The bacterium supplied something revolutionary: a vastly more efficient way to generate energy.

From this intimate alliance emerged the eukaryotic cell – and with it, the possibility of complex life. Every plant, animal and thinking being traces its lineage back to that ancient symbiosis. Our capacity for reflection, imagination and doubt rests upon what was once a free-living microbe. We call these descendants mitochondria.

They persist in nearly every cell of our bodies, hundreds to thousands at a time. In total, we carry an estimated 10 million billion of them – collectively accounting for roughly a 10th of our body mass. Red blood cells are the exception: they lack mitochondria, which maximises oxygen transport. Almost every other cell depends on them absolutely. Neurons are especially demanding hosts. Each contains thousands of mitochondria, occupying up to 40 per cent of its volume.

These rod-shaped structures are often described as the cell’s powerhouses. Through aerobic metabolism, they generate most of the chemical energy that keeps cells alive and functioning – the molecular fuel that sustains every biological process.

Although the brain represents just 2 per cent of body weight, it consumes about 20 per cent of our energy at rest. Every perception, memory, emotion and idea is metabolically expensive. Thought itself is an energy-hungry act. Weight for weight, our brains are more mitochondrial than neural. This is more than a biological curiosity. It suggests that cognition is inseparable from metabolism – that the mind is not only shaped by networks of neurons but by networks of energy.

When I was a doctoral student two decades ago, mitochondria were presented as static ‘powerhouses’ of the cell, dutiful but conceptually dull. Today, they are at the centre of a scientific reappraisal. Far from being passive batteries, mitochondria are dynamic regulators of cellular life and death, stress responses, inflammation and ageing. Increasingly, they are implicated in how clearly we think, how resilient we feel, and how well we adapt to uncertainty.

The scientific picture has shifted dramatically over the succeeding 20 years. In my own work as a neuroscientist, author and broadcaster, I have watched mitochondria move from the margins of biology to the centre of an emerging conversation about how modern lives shape our brains. As I explore in my book The 21st Century Brain: Using Cutting-Edge Neuroscience to Help Us Navigate the Future (2026), a quiet energy crisis may be unfolding within modern bodies.

Sedentary lifestyles, chronic stress, environmental pressures and nutritional excess can paradoxically strain the very systems that sustain cellular power. If cognition is metabolically grounded, then the quality of our thinking may depend – more than we have yet recognised – on the vitality of these ancient symbionts.

To understand how we fuel our thoughts is to revisit the evolutionary bargain that made thought possible in the first place. The story of mitochondria is not simply a tale of cellular energetics. It is a reminder that intelligence emerged from cooperation – and that the clarity of our minds may hinge on the health of an alliance forged billions of years ago.

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The idea that intelligence might depend on energy sounds almost trivial. Of course the brain requires fuel. Yet only recently has it become possible to observe, in living humans, the energetic machinery underlying thought.

At Imperial College London, the molecular psychiatrist Oliver Howes and colleagues used positron emission tomography (PET) scanning to map the distribution of mitochondrial complex I (MC-I) – the largest enzyme in the oxidative phosphorylation pathway that produces ATP, the cell’s energy currency. MC-I functions at the very start of the respiratory chain. Without it, efficient energy production falters.

Monkeys with strong working memory had greater numbers of structurally healthy mitochondria

In a pilot study of healthy volunteers, the team measured participants’ cognitive performance and then scanned their brains to estimate MC-I availability. The finding was striking: higher IQ scores correlated with greater MC-I availability. The interpretation was cautious but suggestive. Cognitive performance appears linked to the brain’s capacity to generate energy within relevant networks. Put simply, the greater the available energy, the greater the potential for complex thought.

Animal research converges on the same theme. At the Icahn School of Medicine at Mount Sinai in New York City, Yuko Hara and colleagues examined synapses in the prefrontal cortex of rhesus monkeys. Working memory – the ability to hold and manipulate information in mind – varied with the density and shape of mitochondria within these synapses. Monkeys with strong working memory had greater numbers of structurally healthy mitochondria. Those with poorer performance showed more malformed mitochondria, consistent with oxidative stress and reduced ATP production.

These findings reinforce a simple but profound conclusion: a brain capable of sophisticated cognition requires a reliable energy system. Intelligence is constrained, in part, by bioenergetics.

We inherit many things from our parents: a turn of phrase, a tendency to melancholy, the architecture of the face. But deep within the cell lies a quieter inheritance, one that arrives exclusively through the mother. The mitochondria – those tiny organelles that generate the chemical energy on which life depends – carry their own DNA. At conception, the egg supplies the embryo with its mitochondrial genome; the mitochondria contributed by the sperm are typically dismantled and destroyed. In this asymmetry of biological bequest, evolution has written a matrilineal script.

This unusual pattern of inheritance has long invited speculation. If mitochondria are the cell’s power plants, and if they are transmitted only along the maternal line, might subtle variations in their DNA shape how we age, even how long we live?

In 2017, Iva Čukić and Ian Deary at the University of Edinburgh published one of the most comprehensive studies ever undertaken on the relationship between intelligence and longevity. Drawing on the Scottish Mental Survey of 1947, they traced more than 70,000 individuals who had sat an IQ test at age 11. Remarkably, they were able to account for 94 per cent of the original cohort, following their survival up to the age of 79.

The scale and duration of the study allowed for unusually firm conclusions. The higher someone’s IQ at 11, the longer they were likely to live. At first glance, this seems counterintuitive. What has intelligence to do with cancer, motor neurone disease or accidents? Yet even these outcomes display statistical correlations with childhood IQ. Such findings provoke uncomfortable questions about causation and mechanism. Intelligence is not a shield against misfortune in any direct sense. Rather, it may reflect a deeper biological integrity – a subtle efficiency in the systems that sustain life.

Ageing may represent a widening gap between energy demand and energy supply

Here the mitochondrion returns to centre stage. The evolutionary biologist David Geary has proposed that mitochondria exist as the linchpin of intelligence, health and ageing. Because mitochondria are responsible for cellular energy production, and because the brain is an energetically voracious organ, even small differences in bioenergetic efficiency could have cumulative effects across the lifespan. Over decades, marginal differences might express themselves as variation in cognitive resilience, physical health and longevity. Ageing itself may be, in part, the story of energy production faltering over time.

Mitochondria continually replicate (mitogenesis) and are selectively removed when damaged (mitophagy). Across the lifespan, both processes decline. Dysfunctional mitochondria accumulate. The resulting inefficiencies have been linked to neurodegenerative disease, cardiovascular disease, intestinal inflammation and cancer.

At the same time, cellular damage accumulates and must be repaired. Repair requires energy. Ageing may therefore represent a widening gap between energy demand and energy supply. As production wanes and costs rise, the body begins to prioritise. Low-priority processes are suppressed. Fatigue, slowed cognition and heightened inflammation follow.

This framing helps explain a central paradox. Oxidative phosphorylation – the process that produces ATP – also generates reactive oxygen species (ROS). At moderate levels, ROS act as essential signalling molecules and can even correlate with higher cognitive performance. But, in excess, ROS damage mitochondrial DNA and cellular structures. Too little energy is debilitating; too much uncontrolled oxidative byproduct is destructive. The brain operates within a narrow energetic corridor. Among people of the same chronological age, differences in vitality, clarity and resilience are often stark. One emerging framework interprets this divergence through bioenergetics.

Energy production is not the only clock governing cellular ageing. Telomeres – protective caps at the ends of chromosomes – shorten with each cell division. When critically shortened, they trigger processes leading to cell death. Telomere length is now widely used as a biomarker of biological ageing.

The enzyme telomerase can restore telomere length, but its activity declines over time and is sensitive to lifestyle and stress. At the University of California, San Francisco, Elissa Epel and colleagues showed that women reporting high chronic stress had significantly shorter telomeres – equivalent to roughly a decade of additional biological ageing – compared with those reporting lower stress.

Chronic stress was associated with both diminished mitochondrial function and declining telomerase

Exercise, by contrast, appears to enhance telomerase activity. So does robust mitochondrial function. Increasingly, evidence suggests intimate links between mitochondrial efficiency and telomere maintenance. Impaired bioenergetics may hasten telomere erosion; robust bioenergetics may buffer against it.

In a consortium study led by Martin Picard at Columbia University in New York City, patients with primary mitochondrial disease displayed elevated resting energy expenditure – a kind of biological hyperinflation in which simply existing carried unusually high energetic costs. Higher energetic strain corresponded to faster telomere erosion.

In another longitudinal study of chronically stressed mothers caring for children with autism, Picard and Epel found that higher baseline mitochondrial health predicted more stable telomerase activity over nine months, whereas chronic stress was associated with both diminished mitochondrial function and declining telomerase. Energy failure and cellular ageing appeared entwined.

If stress impairs mitochondria, and mitochondria help regulate the pace of cellular ageing, then stress is not merely psychological. It is metabolic.

The reach of mitochondrial research has extended into domains once thought too subjective for biology: personality and wellbeing.

An analysis from the long-running Baltimore Longitudinal Study of Aging linked higher mitochondrial DNA copy number in blood cells – a marker of mitochondrial health – with personality traits associated with longevity: extraversion, conscientiousness, openness and agreeableness, alongside lower neuroticism. Replication in an independent Italian cohort strengthened the finding. Mitochondrial health correlated not only with survival but with aspects of temperament.

In a postmortem study at Columbia University led by Caroline Trumpff, older adults who had reported greater life satisfaction and social integration over decades showed higher abundance of mitochondrial proteins in the dorsolateral prefrontal cortex – a region central to executive function and emotional regulation. Positive psychosocial experience was measurably reflected in mitochondrial biology.

Social isolation, on this account, is not only emotionally painful; it may be a part of a bioenergetic tax system

Loneliness offers a counterpoint. In a large-scale analysis of UK Biobank participants, the psychiatrist Barbara Sahakian at the University of Cambridge and colleagues identified growth differentiation factor 15 (GDF15) – a marker of mitochondrial energetic stress – as the protein most strongly associated with social isolation. Elevated GDF15 has been linked to illness, frailty and mortality.

Picard has proposed that the brain continuously monitors bodily energy status – a process he calls ‘metaboception’. When energy demand threatens to outstrip supply, signalling molecules such as GDF15 may initiate conservation responses, experienced subjectively as fatigue or anxiety. Social isolation, on this account, is not only emotionally painful; it may be a part of a bioenergetic tax system.

Notably, in a small, daily-diary study, positive mood predicted improved mitochondrial energy transformation the following day, whereas mitochondrial measures did not predict subsequent mood. Though preliminary, the asymmetry hints that psychological experience may shape cellular energetics more readily than the reverse.

We are accustomed to saying that we ‘feel energised’ by good company. The metaphor may be closer to physiology than we imagined.

In an era preoccupied with cognitive enhancement and artificial minds, it is worth remembering that intelligence depends on sustaining delicate energetic equilibria. To care for our bodies, our relationships and our environment is, in a literal sense, to care for the energy that makes thought possible.

The evolutionary merger that gave rise to mitochondria offers a final lesson. Complexity and intelligence did not emerge from domination but from partnership. Within us, ancient bacteria still labour – not as servants but as collaborators. Every thought we have, every spark of imagination, is powered by this quiet cooperation at the cellular level. Intelligence, in any form, is a partnership with energy itself.

One takeaway is that a brain fit for the 21st century may be one that understands – and respects – its bioenergetic foundations.

The mitochondrial science is still unfolding, but we know enough already to make the following recommendations:

Eat in ways that support energy stabilityDiets centred on minimally processed foods, adequate protein, unsaturated fats (such as those found in oily fish, nuts and olive oil), and fibre-rich vegetables help stabilise glucose supply and reduce oxidative stress. Excess alcohol and smoking, by contrast, place direct strain on mitochondrial membranes and DNA. Nutrient sufficiency – particularly B vitamins, magnesium and CoQ10 – underpins efficient oxidative phosphorylation.

Move daily, and sometimes intenselyPhysical exercise is one of the most potent stimuli for mitogenesis – the creation of new mitochondria. Aerobic activity, in particular, enhances mitochondrial density and efficiency in both muscle and brain. Regular exertion not only improves mood in the short term but enlarges the body’s long-term energetic capacity.

Protect sleep as a biological necessity, not a luxuryDuring sleep, the brain consolidates memory, clears metabolic waste and recalibrates energy balance. Mitophagy – the removal of damaged mitochondria – is supported by consistent circadian rhythms. Chronic sleep restriction, by contrast, leaves energetic debris uncleared, narrowing the corridor between adaptive stress and oxidative overload.

Treat stress as metabolic, not merely emotionalChronic psychological strain translates into measurable changes in mitochondrial function and telomere dynamics. Short bursts of stress can be adaptive; unrelenting stress erodes resilience. Practices that reduce perceived threat – mindfulness, social support, time in nature, deliberate recovery periods – are not indulgences. They are forms of energetic repair.

Invest in social connectionLoneliness is not only subjectively painful; it appears biologically costly. Positive interactions correlate with improved mitochondrial efficiency, while isolation is associated with markers of energetic stress. Relationships are therefore part of our metabolic ecology. Conversation, shared purpose and belonging may help maintain the flow that sustains cognition.

Think in terms of energy budgetsAgeing may reflect a widening gap between energetic demand and supply. Wisdom lies partly in allocating energy where it matters – pruning low-value commitments, embracing restorative practices, and accepting that conservation is not weakness but strategy.

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