Our New Publication: Aging as the Wound That Fails to Heal

How a Bioenergetic Perspective Could Transform the Way We Understand—and Treat—Aging

We’re pleased to share the publication of our latest Perspective article in Biogerontology: “Aging as the Wound That Fails to Heal: A Bioenergetic Continuum of Resolution Failure.”

This work builds on the Exposure-Related Malnutrition (ERM) framework. It offers a new way to understand aging—not as passive wear-and-tear, but as a chronic failure of resolution. In this state, the body remains stuck in an energy-limited, incomplete healing process.

Understanding the Paper's Proposals

Across 12 pages and a central systems-level diagram (Fig. 1, p.4), the paper integrates molecular, metabolic, and regenerative biology into a single continuum. Let’s break down the key points.

1. Aging Resembles a Wound That Never Completes Healing

Ogrodnik’s “unhealed wound” model describes aging as persistent inflammation without regeneration. We extend this by identifying the missing link: insufficient bioenergetic capacity. This lack of energy prevents the body from healing properly.

2. Chronic Stress and Substrate Misallocation Drive “Bioenergetic Exhaustion”

The ERM framework explains how the body reallocates energy toward stress responses and defense—often at the expense of repair. With sustained stress exposure, several issues arise:

• ATP and NADPH levels become insufficient.

• Lipid droplets accumulate.

• Mitochondrial substrate congestion develops.

• Cells shift from OXPHOS to glycolytic “survival mode.”

• Regeneration stalls.

  
  

3. When Energy Cannot Return to Anabolism, Aging Accelerates

The key transition is the failure to move from catabolic containment → anabolic recovery. Once the metabolic cycle collapses, tissues enter a state of:

• chronic inflammation,

• metabolic gridlock,

• impaired repair,

• fibrotic remodeling,

• senescence.

  
  

4. Senescence is Framed as an Energetic Checkpoint

The paper consolidates evidence that senescence is initially reversible when ATP, NAD⁺, and NADPH levels can be restored. Only when energy recovery fails does senescence become irreversible.

Clinical Relevance: Why This Matters for Patient Care

This bioenergetic perspective provides a clinically actionable lens for interpreting metabolic stress, frailty, and chronic disease patterns seen every day in practice.

1. Aging = Accumulated Incomplete Recovery

Clinicians frequently encounter patients who are not “old,” but energetically depleted. This model clarifies why:

• chronic inflammation,

• mitochondrial dysfunction,

• metabolic inflexibility,

• immune suppression or immunosenescence,

• poor wound healing,

often coexist long before overt disease manifests.

2. A Framework for Identifying Early ERM (Exposure-Related Malnutrition)

ERM is proposed as the bioenergetic inflection point where repair becomes constrained. Clinically, this aligns with patterns such as:

• low NAD⁺ status,

• elevated GDF15,

• impaired OXPHOS markers,

• fatigue syndromes,

• redox imbalance,

• micronutrient insufficiency,

• stress-related metabolic shifts.

  
  

These markers may help identify patients at risk of accelerated aging or poor recovery before structural disease manifests.

3. Practical Implications for Intervention

The paper highlights translational strategies that restore catabolic-anabolic cycling, including:

• caloric restriction and time-restricted eating,

• stress-recovery oscillation,

• mitochondrial nutrient support,

• circadian fuel cycling,

• exercise-induced hormesis,

• redox restoration,

• correction of nutrient allocation patterns.

  
  

These approaches may enhance regenerative capacity without overstimulating growth pathways.

The Future of Aging Research

As we delve deeper into the bioenergetic perspective, we can uncover more about how our bodies age. Understanding these mechanisms can lead to better treatment options. It opens the door to innovative therapies that focus on restoring energy balance and enhancing recovery.

Conclusion: A New Lens on Aging

In conclusion, this bioenergetic framework offers a transformative way to view aging. It shifts our understanding from a passive process to an active one, where energy dynamics play a crucial role. By addressing these energy deficits, we can potentially improve health outcomes and quality of life.

Tippairote, T., Hoonkaew, P., Suksawang, A., & Tippairote, P. (2026). Aging as the wound that fails to heal: A bioenergetic continuum of resolution failure. Biogerontology, 27, 7. https://doi.org/10.1007/s10522-025-10356-2