Six Conditions for Viable Zone Maintenance: A Falsifiable Framework for Longevity Research

Author: Mullo Saint
Publisher: American Longevity Science
Published: February 12, 2026
Source: Principia Sanitatis, Volume II, Book VII, Chapters 3-7

Abstract

The pursuit of indefinite healthspan requires a falsifiable theoretical framework. This article presents six necessary and sufficient conditions—derived from control theory and the biology of aging—that must hold for a biological system to remain within its viable operating region indefinitely. These conditions (C1–C6) establish testable criteria for evaluating whether aging can be managed as an engineering control problem. If any condition fails, indefinite healthspan is theoretically impossible; if all conditions hold and interventions of sufficient magnitude exist, it becomes theoretically achievable. Each condition is accompanied by formal definition, biological interpretation, supporting evidence with grading, current measurement approaches, and specific falsification criteria. Condition C6 (Sufficient Control Authority) emerges as the critical empirical uncertainty requiring resolution through rigorous clinical investigation.

1. Introduction

For millennia, aging was considered an immutable law of nature—a process as inevitable as gravity. The 21st century has witnessed the transformation of aging from philosophical mystery to engineering problem. The twelve hallmarks of aging have been systematically characterized. Epigenetic clocks can measure biological age with precision approaching 2-3 years. Interventions ranging from NAD+ precursors to senolytics have demonstrated measurable effects on aging biomarkers.

Yet amid this proliferation of interventions and biomarkers, a fundamental question remains unanswered: Under what conditions is indefinite healthspan theoretically possible? What must be true about biological aging for it to be manageable through continuous intervention? And critically: how would we know if these conditions fail to hold?

This article addresses these questions by establishing a falsifiable framework grounded in control theory. The framework identifies six necessary conditions—Observable State, Bounded Viable Zone, Deterministic Dynamics, Continuous Dynamics, Controllable Dynamics, and Sufficient Control Authority—that collectively determine whether a biological system can be maintained within a healthy operating region indefinitely.

1.1 The Control Theory Perspective

Control theory provides the mathematical foundation for maintaining systems within desired operating regions despite disturbances and drift. Consider a thermostat: it measures temperature (observable state), maintains the room within comfortable bounds (viable zone), responds predictably to heating/cooling (deterministic dynamics), adjusts continuously (continuous dynamics), can influence temperature (controllable dynamics), and has sufficient heating/cooling capacity to counteract external temperature changes (sufficient control authority).

Biological aging presents a fundamentally similar control problem: the state vector drifts toward deterioration, and interventions must maintain state variables within boundaries compatible with healthy function. The six conditions formalize what must be true for this control problem to be solvable.

1.2 The Power of Falsifiability

As Karl Popper established, a theory that cannot be falsified is not a scientific theory. The framework presented here is explicitly designed for empirical testing. Each condition generates specific predictions about what would constitute failure. This is not a weakness—it is the framework's primary strength. By stating falsification criteria clearly, we transform indefinite healthspan from a philosophical aspiration into a testable scientific hypothesis.

2. The Six Conditions

The following sections present each condition with formal mathematical definition, biological interpretation, evidence assessment with grading (A = highest confidence to D = preliminary), current measurement approaches, and falsification criteria.

Condition C1: Observable State (Finite-Dimensional Representation)

Formal Definition:
The aging-relevant state of an individual can be adequately captured by a finite number of state variables X = [E, C, Sen, R, P, F] ∈ ℝ⁶, and these variables can be measured through biomarkers with sufficient precision for monitoring and control.

Biological Interpretation

This condition asserts that despite the staggering complexity of human biology—trillions of cells, countless molecular interactions—the relevant information for aging control can be compressed into a manageable number of measurements. The proposed state vector includes:

  • E (Energy): Cellular energy production capacity, primarily NAD+ levels and mitochondrial function
  • C (Clearance): Autophagy efficiency and proteostasis—the cell's ability to clear damaged components
  • Sen (Senescence): Burden of senescent cells and intensity of SASP (senescence-associated secretory phenotype)
  • R (Regeneration): Stem cell number, function, and tissue repair capacity
  • P (Program): Epigenetic state stability and DNA methylation patterns
  • F (Function): Integrated functional capacity (physical, cognitive, metabolic)

Evidence Supporting C1 Grade A–B

Hallmarks Framework: The twelve hallmarks of aging (López-Otín et al., 2013, 2023) provide finite categorization of major aging processes. This systematization demonstrates that aging mechanisms can be enumerated and classified.

Epigenetic Clocks: Horvath's epigenetic clocks demonstrate that biological age can be predicted from a finite number of CpG methylation sites (hundreds to thousands, but still finite) with precision typically within 2-3 years of chronological age in healthy individuals. Subsequent clocks (GrimAge, PhenoAge, DunedinPACE) trained on mortality and clinical outcomes further validate finite-dimensional representation.

Biomarker Panels: Inflammatory markers (hs-CRP, IL-6), NAD+ measurements, senescence markers (p16INK4a), and functional assessments all provide meaningful, measurable information about underlying aging state.

Current Measurement Approaches

  • E: NAD+ (whole blood, tissue), hs-CRP, mitochondrial respiration assays
  • C: LC3-II/LC3-I ratio, p62/SQSTM1 levels, homocysteine
  • Sen: p16INK4a expression, SASP factors (IL-6, IL-8, MCP-1), GDF-15
  • R: CD34+ circulating progenitors, functional regeneration assays
  • P: Epigenetic clocks (Horvath, GrimAge, DunedinPACE), global methylation
  • F: Grip strength, gait speed, VO₂ max, cognitive assessment (MoCA)

C1 Would Be Falsified If:

  • Aging exhibited essential infinite-dimensional behavior that no finite measurement set could capture
  • No finite set of variables could adequately predict aging outcomes or response to interventions
  • Biomarker measurements had error margins exceeding the Viable Zone width, making control impossible
  • Individuals with identical state vectors had dramatically different aging outcomes, indicating missing variables

Condition C2: Bounded Viable Zone (Safe Operating Region)

Formal Definition:
There exists a well-defined region in state space—the Viable Zone V ⊂ ℝ⁶—within which healthy function is maintained. Formally: V = {X ∈ ℝ⁶ | Xₘᵢₙ ≤ X ≤ Xₘₐₓ}, where states within V maintain health and states outside V lead to dysfunction.

Biological Interpretation

This condition asserts that health is not a single point but a region—a range of biomarker values compatible with proper function. The Viable Zone concept mirrors engineering "safe operating envelopes": aircraft can fly safely across a range of altitudes and speeds, but exceeding boundaries (stall speed, maximum altitude) leads to catastrophic failure.

For biological aging, the Viable Zone represents the region where cellular maintenance, repair, and regeneration outpace damage accumulation. Boundaries are defined by thresholds: NAD+ levels below which autophagy stalls, senescent cell burdens beyond which SASP overwhelms tissue function, epigenetic drift exceeding correction capacity.

Evidence Supporting C2 Grade B

Clinical Homeostatic Ranges: Standard clinical medicine already recognizes viable ranges for biomarkers (glucose 70-100 mg/dL fasting, blood pressure < 120/80 mmHg). Exceeding these boundaries correlates with dysfunction and disease.

Supercentenarian Evidence: The existence of supercentenarians (age 110+) who maintain health into extreme age demonstrates that states exist from which rapid deterioration is not inevitable. These individuals prove that healthy function can be sustained, at least temporarily, at advanced chronological ages.

Intervention Response: Biomarker improvement through intervention (NAD+ restoration, senescent cell clearance) corresponds with functional improvement, suggesting that moving deeper into the Viable Zone enhances health outcomes.

Current Boundary Estimation

Precise Viable Zone boundaries require outcome studies correlating biomarker values with health maintenance. Preliminary thresholds:

Variable Proposed Lower Bound Proposed Upper Bound
NAD+ (Energy) ≥ 80% of young adult reference —
hs-CRP (Clearance) — < 0.5 mg/L (deep clearance)
SASP (Senescence) — IL-6 < 2 pg/mL
DunedinPACE (Program) — < 1.0 (non-aging)
Grip Strength (Function) > 25 kg (age-adjusted) —

C2 Would Be Falsified If:

  • Health were all-or-nothing with no gradation—a binary healthy/sick state with no intermediate region
  • No stable healthy region existed—all individuals eventually crossing into pathology regardless of state values
  • Boundaries shifted unpredictably, making target definition impossible
  • No correlation existed between biomarker values and health outcomes

Condition C3: Deterministic Dynamics

Formal Definition:
The evolution of the state vector over time follows deterministic dynamics that can be characterized and modeled: dX/dt = f(X, t) + ε(t), where f is a deterministic function and ε represents stochastic perturbations of bounded variance.

Biological Interpretation

This condition requires that aging follow predictable laws—that current state and interventions determine future state in a reproducible manner. While biological systems contain stochastic elements (random DNA damage, molecular noise), the underlying dynamics must be lawful enough to enable prediction and control.

The analogy: weather is chaotic and contains randomness, but follows deterministic physical laws (thermodynamics, fluid dynamics). This deterministic substrate enables forecasting. Similarly, aging must have sufficient deterministic structure for intervention planning to be meaningful.

Evidence Supporting C3 Grade A

Biomarker Trajectory Consistency: Epigenetic clocks advance predictably with chronological age. Biological age at one time point strongly predicts biological age at later time points, demonstrating temporal continuity and deterministic drift.

Intervention Reproducibility: Interventions produce consistent, reproducible effects across individuals. NMN supplementation reliably increases NAD+ levels. Senolytics reduce senescent cell burden. Exercise improves VO₂ max. This reproducibility indicates underlying deterministic dynamics.

Gompertz Law: Human mortality doubles approximately every 8 years after age 30—a remarkably consistent exponential relationship observed across populations and time periods. This regularity indicates deterministic aging dynamics at the population level.

Measurement and Modeling

Deterministic dynamics are validated through:

  • Longitudinal studies: Tracking individuals over time to confirm that biomarker trajectories are consistent
  • Intervention trials: Demonstrating that identical interventions produce similar responses across cohorts
  • Mathematical modeling: Building predictive models (differential equations, machine learning) that accurately forecast biomarker evolution

C3 Would Be Falsified If:

  • Aging were fundamentally and irreducibly stochastic—no predictable relationship between current state and future trajectory
  • Identical states produced wildly different trajectories under identical conditions
  • Intervention effects were entirely random with no consistency across individuals
  • No mathematical model, regardless of complexity, could predict aging trajectory better than random chance

Condition C4: Continuous Dynamics

Formal Definition:
The state variables evolve continuously in time without irreversible discontinuous jumps that cannot be prevented by anticipatory control. Formally: for small Δt, ||X(t + Δt) - X(t)|| → 0 as Δt → 0.

Biological Interpretation

This condition requires that aging progresses gradually—that state variables change smoothly rather than undergoing sudden, unpredictable catastrophic transitions. Continuity enables anticipatory control: if variables drift slowly enough, monitoring can detect approaching boundaries and trigger corrective intervention before failure occurs.

Critical distinction: acute events like stroke or heart attack appear discontinuous, but they arise from continuous deterioration of underlying state variables (atherosclerosis, endothelial dysfunction, inflammatory burden). If these variables are monitored, the "sudden" event becomes predictable and potentially preventable.

Evidence Supporting C4 Grade B–C

Epigenetic Clock Continuity: Epigenetic age advances smoothly and continuously. Horvath clocks do not exhibit sudden jumps; they track gradual methylation changes accumulating over years.

Biomarker Trajectories: NAD+ levels decline progressively with age. hs-CRP increases gradually. Senescent cell burden accumulates incrementally. These are continuous processes, not step functions.

Pre-Disease Detection: Cardiovascular events are preceded by measurable deterioration in arterial stiffness, inflammatory markers, and endothelial function. Cancer is preceded by accumulating mutations and immune escape. These findings suggest that seemingly sudden failures have continuous antecedents.

The Challenge of Rare Discontinuities

The primary threat to C4 would be truly random, catastrophic aging events with no continuous precursors—biological equivalents of sudden hardware failure. Current evidence suggests most "sudden" aging events have detectable prodromal phases, but this requires further validation, particularly for rare events.

C4 Would Be Falsified If:

  • Aging occurred through irreversible, unpredictable catastrophic transitions that no amount of monitoring could anticipate
  • State variables exhibited discontinuous jumps with no continuous precursors
  • Measurement at arbitrarily fine intervals could not predict sudden failures
  • The majority of age-related dysfunction arose from truly random events rather than accumulated continuous deterioration

Condition C5: Controllable Dynamics

Formal Definition:
For each state variable Xᵢ, there exist interventions uᵢ that can modify its dynamics in desired directions: dX/dt = f(X, u), where u represents the intervention vector and control authority ∂f/∂u ≠ 0.

Biological Interpretation

This condition requires that aging dynamics are not merely observable and deterministic—they must also be modifiable. For each state variable, interventions must exist that can influence its trajectory. Controllability is the difference between weather (observable, deterministic, but largely uncontrollable) and indoor climate (observable, deterministic, and controllable via HVAC).

Evidence Supporting C5 Grade A–B

C5 is among the most strongly supported conditions. For each state variable, interventions with demonstrated effects exist:

Variable Intervention Demonstrated Effect Evidence
Energy (E) NMN/NR, exercise 40–100% NAD+ increase Grade B
Clearance (C) Rapamycin, fasting, spermidine Enhanced autophagy, reduced inflammation Grade B–C
Senescence (Sen) Dasatinib + Quercetin, Fisetin Senescent cell burden reduction Grade B
Regeneration (R) Resistance training, BPC-157 Improved stem cell function, tissue repair Grade B–C
Program (P) Yamanaka factors, alpha-ketoglutarate Epigenetic age reversal (in vitro) Grade A (cells), C (humans)
Function (F) Exercise, cognitive training Improved physical and cognitive function Grade A

Caloric Restriction: Modifies aging trajectory across multiple species, demonstrating controllability at the organismal level (Grade A in model organisms).

Epigenetic Reprogramming: Yamanaka factors can reverse aspects of cellular aging without full dedifferentiation, demonstrating that even the "program" variable is modifiable (Grade A in cell culture and mice).

C5 Would Be Falsified If:

  • Aging dynamics were completely unresponsive to any intervention
  • One or more state variables exhibited no response to any known or potential intervention
  • Intervention effects were purely placebo or measurement artifacts rather than genuine biological changes
  • Control authority ∂f/∂u = 0 for all intervention vectors

Condition C6: Sufficient Control Authority

Formal Definition:
Available interventions are powerful enough to counteract the drift toward deterioration at the Viable Zone boundary indefinitely. Formally: ||dX/dt|drift|| ≤ ||∂f/∂u · u|| for sustainable intervention magnitudes u.

Biological Interpretation

This is the most demanding and uncertain condition. C5 establishes that interventions exist; C6 requires that they are powerful enough. The distinction is critical: a thermostat can control temperature (C5), but if the heater is too weak for the building size, it cannot maintain temperature on a cold day (C6 fails).

For aging, C6 asks: Can current or foreseeable interventions generate sufficient corrective force to counteract aging drift indefinitely? This is the central empirical question determining whether indefinite healthspan is achievable with present technology or requires fundamental breakthroughs.

Evidence Supporting C6 Grade C–D

Partial Support from Preclinical Studies:

  • Rapamycin extends lifespan 10-25% in mice (Grade A in mice)
  • NMN/NR raise NAD+ levels 40-100% in humans (Grade B)
  • Senolytics reduce senescent burden measurably (Grade B)
  • Epigenetic reprogramming reverses cellular age in vitro (Grade A in cells)

These findings demonstrate intervention magnitude is non-trivial, but they do not prove sufficiency for indefinite human healthspan.

Evidence Creating Uncertainty About C6 Grade D

  • Preclinical vs. Clinical Gap: Most evidence is from cell culture or model organisms. Human translation may reduce effect sizes.
  • Unknown Drift Rates at Advanced Ages: Aging may accelerate nonlinearly; drift rates at age 80+ may exceed intervention capacity.
  • Long-Term Sustainability Unknown: Can interventions be sustained for decades without cumulative side effects or tachyphylaxis?
  • Combinatorial Effects Uncharacterized: Multi-intervention protocols may have synergistic or antagonistic interactions that alter net control authority.

C6 Is the Critical Empirical Question

All other conditions (C1–C5) are well-supported by current evidence. C6 remains uncertain. The framework predicts what magnitude would be sufficient; empirical research must verify whether current or future interventions meet that standard.

Importantly, C6 failure would be informative: the framework would specify how much more control authority is needed, guiding therapeutic development priorities.

C6 Would Be Falsified If:

  • Drift rates exceeded what any combination of interventions could counteract
  • Interventions that affect state variables were insufficient in magnitude to prevent Viable Zone boundary crossing
  • Cumulative side effects made long-term intervention unsustainable
  • Tachyphylaxis (declining response over time) eliminated intervention effectiveness
  • Aging drift accelerated faster than intervention capacity could scale

3. The Falsification Framework

3.1 Why Falsifiability Matters

Karl Popper established falsifiability as the demarcation criterion separating science from pseudoscience. A theory that cannot be tested—that makes no predictions distinguishable from alternatives—has no scientific content. The Six Conditions framework is explicitly designed for empirical refutation.

This is not a weakness. It is the framework's primary intellectual virtue. By stating falsification conditions clearly, we transform indefinite healthspan from philosophical speculation into testable hypothesis. Each condition generates specific empirical predictions. Experiments can be designed to evaluate whether these predictions hold.

3.2 What Falsification Would Reveal

Crucially, falsification of any condition would be informative—it would clarify what is needed:

In every case, falsification clarifies the path forward rather than terminating inquiry.

3.3 Current Status: Condition-by-Condition Assessment

The conditions are ordered by certainty based on available evidence:

Condition Certainty Evidence Grade Status
C5 (Controllability) High A–B Well-Supported
C3 (Deterministic) High A Well-Supported
C1 (Observable) Moderate-High A–B Well-Supported
C2 (Bounded Viable Zone) Moderate B Supported
C4 (Continuous) Moderate B–C Supported
C6 (Sufficient Magnitude) Low-Moderate C–D Uncertain — Critical Test

Five of six conditions are well-supported by existing evidence. C6 remains the critical uncertainty requiring resolution through rigorous clinical investigation.

4. A Research Program for Rigorous Testing

The falsification conditions suggest a concrete research program:

4.1 Validate State Variables (C1 Test)

4.2 Calibrate Viable Zone Boundaries (C2 Test)

4.3 Improve Measurement Precision (C1, C4 Test)

4.4 Test Intervention Sufficiency (C6 Test — THE PARAMOUNT QUESTION)

This is the critical empirical question. Required studies:

4.5 Timeline and Resources

A rigorous test of C6 requires:

5. Discussion

5.1 The Innovation: A Falsifiable Framework

Prior discussions of indefinite healthspan often treat it as speculative futurism—aspirational but untestable. The Six Conditions framework transforms this speculation into rigorous hypothesis. By formalizing necessary and sufficient conditions with explicit falsification criteria, the framework enables scientific evaluation.

The key insight: If any condition fails, indefinite healthspan is impossible. If all conditions hold and interventions of sufficient magnitude exist, it becomes theoretically achievable. This provides a decision tree for the field: test each condition; identify failures; address gaps; iterate.

5.2 The Path Forward

Current evidence strongly supports C1-C5. These conditions establish that aging is observable, operates within bounded regions, follows deterministic laws, progresses continuously, and responds to interventions. These are non-trivial findings—they rule out entire classes of alternative hypotheses (aging as infinite-dimensional chaos, fundamentally random, or completely uncontrollable).

C6 remains uncertain. Whether current interventions have sufficient magnitude to counteract aging drift indefinitely is the empirical question requiring resolution. This is not a conceptual problem—it is an engineering parameter that can be measured.

5.3 What Success Looks Like

Validation of all six conditions would not prove that indefinite healthspan has been achieved. It would prove that indefinite healthspan is theoretically achievable with sufficient intervention intensity, and that current or foreseeable interventions approach the required magnitude.

This shifts the problem from "Is this possible?" to "How do we optimize implementation?" The latter is a tractable engineering problem amenable to systematic improvement.

5.4 The Urgency

Approximately 100,000 people die daily from age-related causes—two-thirds of global mortality. Every day of delay in resolving the C6 question costs more lives than most natural disasters. The urgency is absolute, even if normalized into invisibility by ubiquity.

The framework presented here provides the theoretical architecture for systematic investigation. The tools exist. The biomarkers exist. The interventions exist. What remains is coordinated empirical effort at sufficient scale and duration to test whether intervention magnitude is sufficient.

6. Conclusion

This article has presented six necessary and sufficient conditions for indefinite healthspan maintenance, derived from control theory and aging biology. Each condition has been specified with formal mathematical definition, biological interpretation, evidence grading, measurement approaches, and falsification criteria.

Five conditions (C1-C5) are well-supported by current evidence. C6—Sufficient Control Authority—remains the critical empirical uncertainty. Resolution requires rigorous, long-term clinical trials evaluating whether intervention combinations can maintain aging biomarkers within the Viable Zone indefinitely.

The framework's power lies not in its certainty but in its falsifiability. Each condition generates testable predictions. Failure would clarify what is needed. Success would validate theoretical achievability and guide optimization.

We stand at a threshold. The theoretical architecture exists. The measurement tools exist. The interventions exist. What remains is the collective will to conduct the decisive empirical test—to answer, once and for all, whether aging must be accepted or can be managed.

Key Takeaway

Indefinite healthspan is not a question of philosophy or futurism. It is a question of measurable parameters: Can interventions generate corrective force exceeding aging drift? The Six Conditions framework transforms this from speculation into testable hypothesis. The next decade of longevity research should be organized around answering this question rigorously.

References

This article is derived from Principia Sanitatis (Volume II, Book VII, Chapters 3-7) by Mullo Saint. For complete citations, mathematical proofs, and clinical implementation protocols, consult the full manuscript.

Core Literature Cited