When Cells Compete: How Energy Economics Shapes Health, Aging, and Cancer

Imagine your body as a living economy. Every cell is a citizen drawing from a shared pool of energy, nutrients, and oxygen. When resources are scarce, the system must decide: which cells are worth the investment?

Nature has already solved this problem through a remarkable process known as cell competition—a quality-control mechanism that ensures tissues remain efficient, adaptive, and resilient.

A recent review by Jules Lavalou and colleagues in Current Opinion in Cell Biology (2025), titled “Mechanisms of cellular fitness and cell competition: Towards an integrated view,” offers a sweeping synthesis of how cells “audit” one another’s bioenergetic performance to maintain tissue integrity. Their work provides a molecular blueprint for understanding how health, aging, and even cancer can be viewed through the lens of energy allocation.

A Cellular Survival Game: Winners and Losers

Within tissues, not all cells are equal.

• Winner cells are metabolically robust: they maintain high mitochondrial membrane potential, efficient oxidative phosphorylation (OXPHOS), and balanced redox and proteostasis networks.

• Loser cells, by contrast, show low mTOR and c-MYC activity, elevated p53 signaling, reduced ATP output, and activation of the Integrated Stress Response (ISR)—a cellular brake that suppresses protein synthesis and ramps up stress-defense genes.

In early embryos, for example, loser cells with poor mitochondrial performance or damaged DNA are removed via apoptosis, ensuring only the most efficient cells contribute to development. This same process continues subtly in adult tissues, pruning damaged cells and preserving functional balance.

Metabolism as the Engine of Cellular Fitness

At the molecular level, energy metabolism defines competitive status.

• mTOR (mechanistic target of rapamycin) acts as a nutrient sensor. When active, it promotes growth, ribosome biogenesis, and protein synthesis—but also raises energy demand.

• AMPK (AMP-activated protein kinase) counters mTOR, signaling when ATP is low and pushing cells toward energy conservation and repair.

• c-MYC, a transcriptional amplifier, increases mitochondrial biogenesis and glycolytic flux, but if its downstream resources (amino acids, oxygen) are insufficient, the resulting imbalance triggers p53 activation and cell death.

This metabolic tug-of-war defines who survives. Cells that can sustain ATP supply and manage reactive oxygen species (ROS) remain in the game. Those that cannot are energetically bankrupt.

Lavalou’s review also shows how metabolite flows influence competition. In Drosophila models, “winner” cells siphon lactate from “loser” neighbors to feed their TCA cycle—a literal energy transfer within the tissue micro-economy.

Proteostasis: When Quality Control Fails

Beyond metabolism, protein homeostasis (proteostasis) is another determinant of fitness.

Cells with ribosomal mutations—called Minute mutants—accumulate misfolded proteins and activate stress kinases (JNK, eIF2α phosphorylation) and transcription factors like Xrp1 and Nrf2.These stress loops amplify proteotoxic burden, marking the cell for elimination.

Interestingly, mTOR inhibition or autophagy activation can rescue these cells, showing that restoring the balance between anabolism (protein synthesis) and catabolism (clearance) re-stabilizes their energy economy.

Mechanical Fitness: Energy Meets Architecture

Even the physical structure of cells feeds into this bioenergetic calculus.

Cells with lower stiffness or weaker adhesion are more easily compressed and extruded from epithelial layers.

Here, molecules like YAP (Yes-associated protein) act as mechanical-metabolic transducers:

• High YAP activity enhances cytoskeletal tension, increases glycolysis, and supports survival.

• Low YAP activity signals loss of mechanical fitness, triggering Hippo pathway activation and elimination.

Through these intertwined signals—mTOR, MYC, p53, YAP, Nrf2—the cell continuously integrates energy status, mechanical pressure, and proteostatic balance to determine whether to persist or withdraw.

The ERM Lens: Bioenergetic Economy of Tissues

Within the Exposure-Related Malnutrition (ERM) framework, cell competition mirrors how the body manages energy during stress and recovery.

Healthy tissue functions like a balanced market:

• Energy flows to efficient producers (healthy mitochondria).

• Defective or energy-hungry cells are retired to protect systemic balance.

This dynamic reflects the same adaptive cycle that governs whole-body resilience—Respond → Adapt → Resolve → Renew.

When resolution fails, energy debt accumulates, and maladaptation spreads from the cellular to the systemic level.

Bioenergetic Triage from Mitochondria to Tissues

The concept of cell competition as tissue-level bioenergetic triage extends all the way down to the mitochondria themselves.

Inside each cell, mitochondria perform their own version of survival economics. Under energy crisis, they divide (fission) to isolate damaged segments, fuse to share membranes and genetic components, and even transfer between cells to rescue energy-depleted neighbors.

These dynamic behaviors are guided by molecular regulators such as DRP1 (for fission), MFN1/2 and OPA1 (for fusion), and Miro1 or tunneling nanotubes (for intercellular transfer).

Through these mechanisms, mitochondria collectively preserve bioenergetic integrity across the cellular network.

Thus, the same principle of energetic prioritization governs both scales:

• Within the cell, mitochondrial quality control ensures efficient energy production.

• Within the tissue, cell competition ensures efficient energy utilization.

Resilience emerges when both layers of this hierarchy—organelle and tissue—are synchronized in their ability to allocate, recycle, and renew energy.

When the Market Crashes: Hyperinsulinemia and Energy Distortion

Here’s where the connection to insulin resistance and cancer becomes profound.

Lavalou’s review notes that hyperinsulinemia, a hallmark of early insulin resistance, disrupts the fairness of this cellular economy.

Chronically elevated insulin keeps PI3K–Akt–mTOR signaling turned on, regardless of true energy status.

This acts like a constant flow of unearned subsidies—allowing energetically inefficient or damaged (“loser”) cells to survive and even expand.

In this skewed environment:

• Normal metabolic checkpoints (AMPK, p53) are overridden.

• Autophagy and ISR are suppressed, impairing cellular cleanup.

• Damaged mitochondria persist, producing ROS that further mutate DNA.

• Clones with oncogenic mutations (Ras, PI3KCA, or YAP-high) exploit insulin signaling to gain dominance.

Essentially, hyperinsulinemia removes the energy-based accountability system that keeps cellular populations fit.

Loser cells no longer face bankruptcy—they’re artificially sustained.

Over time, this energy misallocation manifests as tissue inefficiency, pre-malignant overgrowth, and carcinogenesis.

In metabolic terms, insulin resistance is the macro-scale symptom of the same process: the body’s energy flow becomes trapped in a state of chronic anabolic signaling, unable to clear the cellular debts of stress and damage.

Restoring the Natural Market of Energy

Rebalancing this system requires more than lowering blood sugar—it demands re-establishing the rhythm of energetic flux:

• Periodic fasting and circadian alignment allow catabolic phases for cleanup.

• Exercise re-sensitizes tissues to insulin while promoting mitochondrial renewal.

• Nutritional sufficiency (amino acids, micronutrients) supports the anabolic rebound.

• Redox modulation (e.g., glutathione, NAD⁺ balance) maintains cellular audit capacity.

Through the ERM lens, these interventions aren’t merely metabolic tweaks—they restore fairness to the bioenergetic economy, allowing tissues to allocate resources based on true fitness once again.

Final Reflection

What Lavalou and colleagues describe at the cellular level is the same principle you see across biology:

Resilience is not the absence of stress—it’s the efficiency of recovery and renewal.

When hyperinsulinemia, chronic stress, or nutrient imbalance distort this internal marketplace, cells that should retire stay alive, consuming energy without contributing to repair. Over time, these inefficiencies scale upward—from mitochondria to tissues to the whole organism—culminating in disease.

Re-establishing the bioenergetic fairness that evolution built into our cells may be one of the most powerful strategies we have to prevent cancer, slow aging, and restore resilience.

References:

Lavalou J, Kulakova K, Subramaniam YJ, & Piddini E. (2025). Mechanisms of cellular fitness and cell competition: Towards an integrated view. Current Opinion in Cell Biology, 96, 102571.