The Preservation of Functional Reserve: A Control Systems Framework for Human Aging.

The dominant clinical manifestation of aging is not mortality but the progressive depletion of functional reserve-the surplus physiological capacity separating independent function from disability. Existing geroscience frameworks describe molecular aging in detail yet give the point-of-care clinician little basis for prioritizing targets. We reframe functional aging as a control systems problem in which aging is modeled as progressive instability within a coupled, bidirectional mitochondrial-epigenetic axis. That axis is called central in two limited senses only: network connectivity and therapeutic tractability; no causal primacy is claimed over mTOR signaling, inflammaging, senescence, proteostasis failure, telomere attrition, or stem cell exhaustion. Candidate capacities were scored against three conjunctive criteria-independence, necessity, and modifiability. Five satisfy them at the thresholds stated, and sensitivity analysis reports which threshold changes would instead yield four or seven, so the count follows from a stated procedure rather than standing as a natural constant. Interventions are mapped onto these capacities in a separate layer. The result is a hierarchically ordered, clinically actionable, falsifiable architecture in which functional reserve is the primary therapeutic target and lifespan a downstream consequence-and whose primary test, deletion of any single capacity from longitudinal models, is evaluable in existing cohorts without new data collection.