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

Vollständiger Abstract

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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.