What We Still Don’t Know About Aging

Why Energy, Recovery, and Resilience Matter

A new paper in GeroScience by Talay and colleagues (2025), titled “Open problems in ageing science: a roadmap for biogerontology,” does something both rare and valuable in modern science: it pauses progress long enough to ask what we still don’t understand.

Rather than proposing another intervention or biomarker, the authors curated 100 open questions that remain unresolved in aging research—from the molecular to the clinical level. Their message is clear: despite remarkable advances, aging science still lacks consensus on its most fundamental issues.

This paper is not about answers. It’s about priorities. And that’s exactly why it matters.

But it also reveals something important by omission—something that frameworks like Exposure-Related Malnutrition (ERM) are designed to address.

The Key Message of the Paper:

We’re Asking Many Questions, But Not Always the Right Ones

The authors show that aging research is highly imbalanced:

• A small set of familiar questions (e.g., “Why do we age?” or “What are the molecular mechanisms of aging?”) dominates the literature.

• Many questions that are likely critical for translation—especially those involving recovery capacity, resilience, and system dynamics—are barely studied at all.

One striking example is a question with almost no representation in the literature:

How can we measure the extent and pace of changes in the homeodynamic space during aging?

In simpler terms: How do we measure the body’s capacity to adapt, recover, and restore balance over time?

This is not a niche question. It is central to how people experience the aging process.

What’s Missing:

Aging Is Still Framed as Damage, Not Failed Recovery

Although the paper is broad and thoughtful, it largely reflects how aging science has traditionally been framed:

• Aging as the accumulation of damage

• Aging as molecular and cellular decline

• Aging as something to be slowed, blocked, or reversed

What is largely missing is a process-level view of aging as unresolved adaptation.

Very few of the open questions explicitly ask:

• What happens when stress responses are repeatedly activated but never fully resolved?

• How does chronic energetic strain limit repair, regeneration, and immune tolerance?

• When does adaptation quietly turn into depletion?

These are not philosophical questions. They are clinical ones.

Where the ERM Framework Fits In

The Exposure-Related Malnutrition (ERM) framework starts from a different premise:

You’re not aging faster because you’re broken.You’re aging faster because you’re exhausted.

ERM describes aging as a progressive failure of energetic resolution driven by chronic exposures—psychological, metabolic, inflammatory, environmental, infectious, and nutritional.

Instead of asking only what damage accumulates, ERM asks:

• Is the body still able to complete the stress–adaptation–recovery cycle?

• Is there sufficient bioenergetic availability to support repair?

• Are resources being diverted away from long-term maintenance toward short-term survival?

Seen through this lens, many of the “open problems” highlighted in the paper suddenly connect.

Re-interpreting the Open Questions Through an ERM Lens

Several underexplored questions identified by Talay et al. align almost perfectly with ERM:

• Homeodynamic space → ERM reframes this as recovery bandwidth

• Biomarkers of aging → ERM asks whether biomarkers measure damage or unresolved debt

• Mitochondrial dysfunction → ERM emphasizes congestion and misallocation, not just failure

• Interventions → ERM asks whether therapies restore capacity or merely suppress signals

• Immune aging → ERM views chronic immune activation as an energetic tax, not an isolated defect

What’s missing in the roadmap is not molecular detail—but integration across time, stress, and energy availability.

Why This Matters for Real People

Most people don’t experience aging as a sudden molecular collapse. They experience it as:

• Slower recovery

• Lower tolerance to stress

• Lingering inflammation

• Fatigue that doesn’t resolve

• Loss of resilience long before disease appears

Aging, in practice, looks like maladaptation without recovery.

ERM offers a framework that:

• Explains why early aging phenotypes can appear reversible

• Helps stage vulnerability before irreversible decline

• Bridges molecular biology with lived clinical experience

Moving Forward:

From Damage Control to Capacity Restoration

The GeroScience paper is an important contribution. It reminds the field that progress depends on question quality, not just technical sophistication.

But the next step is clear:

We need aging models that explicitly account for:

• Energy availability

• Recovery dynamics

• Adaptive resolution

• Cumulative exposure burden

Not as side notes—but as organizing principles.

If aging science is to move from describing decline to preserving resilience, frameworks like ERM are not alternatives to existing biology. They are integrators of it.

Final Thought

Aging may not be primarily a story of things breaking down.

It may be a story of systems that never get the chance to recover fully.

And that is a much more hopeful story—because recovery, unlike time, can sometimes be restored.

Talay, A., Belikov, A. V., To, P. K. P., Alfatemi, H. H., Alon, U., Deelen, J., Ewald, C. Y., Gems, D., Gorbunova, V., Gruber, J., Hägg, S., Hemming, J., Horvath, S., Kaya, A., Lewis, C. J., Maier, A. B., Marinova, M. B., Pawelec, G., Peleg, S., Rattan, S. I. S., Scheibye-Knudsen, M., Schmauck-Medina, T., Saroyan, V., Seluanov, A., Stolzing, A., Teeling, E., Williams, R. W., White, T., Unfried, M., & de Magalhães, J. P. (2025). Open problems in ageing science: A roadmap for biogerontology. GeroScience. https://doi.org/10.1007/s11357-025-01964-4