Open problems · P1
Mitochondrial efficiency: marker or mechanism?
As people age and accumulate allostatic load, the efficiency with which mitochondria turn fuel into usable energy declines. Is that decline just one more marker of load, or a measurable mechanism that drives the loss of stability and the move from adaptation into disease?
Why it matters
This is the model's main open question. If falling mitochondrial efficiency is the mechanism, the PFL becomes a way to predict when adaptation is close to failing, not only a new picture of allostatic load. If it is only a marker, it adds a measurement but not a cause.
What exists
- Recovery-time and early-warning tests near measurable edges in MIDUS (Mountainside) and the stability analysis (Stability).
- The allostasis model with load and capacity as two coupled states (Allostatic load).
- Requested: cohorts that measure mitochondrial function directly (muscle phosphocreatine recovery by magnetic resonance spectroscopy, or respirometry on biopsies) alongside repeated routine blood tests and outcomes.
A first step
Write down the two versions as models: efficiency as a readout of load, and efficiency as the capacity term that sets how close a person is to the fold. Derive what each predicts for recovery time, reactivity and the order in which markers change, then name the smallest study that could tell them apart.