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Structured Evidence Base

Curated, classified, and continuously updated.

The literature operating beneath the BAM framework. Tier-classified by methodology. System-mapped against the system architecture. Reviewed on a defined cadence.

Library Composition

Strong Evidence

292

Moderate Evidence

60

Emerging Evidence

425

Contextual Foundations

0

Total References

777

Four Tiers · Methodology-graded

Every reference enters the library at one of four tiers, classified by study methodology rather than topic appeal. Tier discipline is what separates a structured evidence base from a citation list.

292

T-01

Strong Evidence

Meta-analyses · Large RCTs · Cochrane

60

T-02

Moderate Evidence

Cohort · Prospective · Longitudinal

425

T-03

Emerging Evidence

Reviews · Mechanistic · Pilot · Case

0

T-04

Contextual Foundations

Textbooks · Narrative · Historical

Nine Systems · One Taxonomy

Every reference mapped against the same architecture operated by the Index.

D-01

Structural

777 refs

D-02

Oral-Systemic

0 refs

D-03

Metabolic

0 refs

D-04

Neurological

0 refs

D-05

Autonomic

0 refs

D-06

Recovery

0 refs

D-07

Toxic

0 refs

D-08

Regenerative

0 refs

D-09

Hormonal &
Endocrine

0 refs

Evidence Integration Model

How the Library Feeds the System

Evidence is not displayed. It is operated. Each reference flows into one of three integration points — none of them ornamental.

I-01

System Scoring

Tier 1–2 evidence calibrates the threshold curves used to score each system. The framework refuses to assign a system weight that lacks a strong-or-moderate evidence anchor.

F-02

Cross-System Relationships

Tier 1–3 evidence supports the cross-system correlation map — the interaction profile that distinguishes BAM from single-biomarker models.

F-03

System Output

Evidence governs how composite ALRI is constructed, classified, and translated into governance-grade output. Every banding decision traces back to a documented source.

Literature → Tier Classification → System Mapping → Integration ALRI

Search by System, Tier, or Relevance

The library is exposed in full under structured query — never as a flat catalogue. Filter by tier, by system, or by keyword to inspect the references underneath any framework decision.

TIER 3

D-01 · Structural

On the Concept of Health Capital and the Demand for Health

Grossman M. · 1972 · J Political Economy, 1972

TIER 3

D-01 · Structural

The economic value of targeting aging

Scott AJ, Ellison M, Sinclair DA. · 2021 · Nature Aging, 2021

TIER 3

D-01 · Structural

Does Preventive Care Save Money?

Cohen JT, Neumann PJ, Weinstein MC. · 2008 · NEJM, 2008

TIER 3

D-01 · Structural

Systems medicine and the emergence of proactive P4 medicine: predictive, preventive, personalized, participatory

Hood L, Flores M. · 2012 · New Biotechnology, 2012

TIER 1

D-01 · Structural

General health checks in adults for reducing morbidity and mortality

Krogsboll LT et al. · 2012 · BMJ (Cochrane), 2012

TIER 3

D-01 · Structural

DNA methylation age of human tissues and cell types

Horvath S. · 2013 · Genome Biology, 2013

TIER 2

D-01 · Structural

DunedinPACE, a DNA methylation biomarker of the pace of aging

Belsky DW, Caspi A et al. · 2022 · eLife, 2022

TIER 3

D-01 · Structural

Epigenetic-based age acceleration: associations with aging-related morbidity and mortality

Faul JD et al. · 2023 · PNAS, 2023

TIER 3

D-01 · Structural

Heavy Metal Exposure and Cardiovascular Disease

Pan Z et al. · 2024 · Circulation Research, 2024

TIER 2

D-01 · Structural

Toxic metals and chronic kidney disease

Moody EC et al. · 2018 · Curr Environ Health Reports, 2018

TIER 3

D-01 · Structural

35 meta-analyses, 29M+ participants

Heavy metal umbrella review · 2024 · J Hazardous Materials, 2024

TIER 3

D-01 · Structural

Long-term PM2.5 exposure and mortality (WHO-commissioned)

Orellano P et al. · 2024 · Int J Public Health, 2024

TIER 3

D-01 · Structural

Indoor VOCs health effects 1980–2017

Liu N et al. · 2022 · Indoor Air, 2022

TIER 3

D-01 · Structural

Persistent organic pollutants and metabolic disease risk

Ruzzin J et al. · 2012 · BMC Public Health, 2012

TIER 3

D-01 · Structural

Modulation of Metabolic Detoxification Pathways Using Foods

Hodges RE et al. · 2015 · J Nutr Metab, 2015

TIER 3

D-01 · Structural

Genetic Biomarkers of Metabolic Detoxification for Personalized Lifestyle Medicine

Aronica L et al. · 2022 · Nutrients, 2022

TIER 3

D-01 · Structural

Diversity, stability and resilience of the human gut microbiota

Lozupone CA et al. · 2012 · Nature, 2012

TIER 3

D-01 · Structural

The Microbiota-Gut-Brain Axis

Cryan JF et al. · 2019 · Physiological Reviews, 2019

TIER 3

D-01 · Structural

Interaction between microbiota and immunity

Zheng D, Liwinski T, Elinav E. · 2020 · Cell Research, 2020

TIER 3

D-01 · Structural

Gut microbiota associated with immune cell dynamics in humans

Schluter J, Peled JU et al. · 2020 · Nature, 2020

TIER 3

D-01 · Structural

Natural cytotoxic activity and cancer incidence: 11-year follow-up

Imai K et al. · 2000 · The Lancet, 2000

TIER 3

D-01 · Structural

NK cell-mediated immunosurveillance of human cancer

Malmberg KJ et al. · 2017 · Semin Immunol, 2017

TIER 1

D-01 · Structural

Leukocyte count and all-cause/cardiovascular mortality: meta-analysis

Park C et al. · 2023 · Am J Cardiol, 2023

TIER 3

D-01 · Structural

CRP and risk of CHD, stroke, and mortality

Kaptoge S et al. · 2010 · The Lancet, 2010

TIER 2

D-01 · Structural

hs-CRP and all-cause, cardiovascular, and cancer mortality

Li Y et al. · 2017 · Atherosclerosis, 2017

TIER 3

D-01 · Structural

Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty

Ferrucci L et al. · 2018 · Nature Reviews Cardiology, 2018

TIER 3

D-01 · Structural

Inflammation and aging: signaling pathways and intervention therapies

Li X et al. · 2023 · Signal Transduction Targeted Therapy, 2023

TIER 1

D-01 · Structural

IL-6, TNF, IL-1β and age-related diseases: meta-analysis

Tylutka A et al. · 2024 · Frontiers Immunology, 2024

TIER 3

D-01 · Structural

Serum ferritin as inflammatory disease marker

Kell DB et al. · 2014 · Metallomics, 2014

TIER 3

D-01 · Structural

Ferritin and cardiovascular/all-cause mortality

Kadoglou NPE et al. · 2017 · PLOS ONE, 2017

TIER 3

D-01 · Structural

Fasting glucose and cause-specific death

Seshasai SRK et al. · 2011 · NEJM, 2011

TIER 2

D-01 · Structural

Metabolic syndrome and all-cause mortality

Wu SH, Liu Z, Ho SC. · 2010 · Eur J Epidemiol, 2010

TIER 3

D-01 · Structural

Waist circumference as a vital sign: IAS/ICCR Consensus

Ross R et al. · 2020 · Nature Reviews Endocrinology, 2020

TIER 3

D-01 · Structural

Mitochondria in health, disease, and aging

Harrington JS et al. · 2023 · Physiological Reviews, 2023

TIER 3

D-01 · Structural

Mitochondrial and metabolic dysfunction in ageing

Miwa S et al. · 2022 · Nature Reviews Endocrinology, 2022

TIER 3

D-01 · Structural

Cardiorespiratory fitness as predictor of all-cause mortality and CV events

Kodama S et al. · 2009 · JAMA, 2009

TIER 2

D-01 · Structural

CRF is a strong predictor of morbidity and mortality: overview of meta-analyses

Lang JJ et al. · 2024 · Br J Sports Med, 2024

TIER 3

D-01 · Structural

VOâ‚‚max: a key predictor of longevity?

Strasser B, Burtscher M. · 2018 · Frontiers Bioscience, 2018

TIER 1

D-01 · Structural

HRV in prediction of mortality: meta-analysis

Jarczok MN et al. · 2022 · Neurosci Biobehav Rev, 2022

TIER 3

D-01 · Structural

HRV and Exceptional Longevity

Hernandez-Vicente A et al. · 2020 · Frontiers Physiology, 2020

TIER 3

D-01 · Structural

HRV and ANS imbalance: biomarkers of aging and inflammaging

Olivieri F et al. · 2024 · Ageing Research Reviews, 2024

TIER 3

D-01 · Structural

ANS imbalance during aging impairs anti-inflammaging strategies

Giunta S et al. · 2024 · GeroScience, 2024

TIER 1

D-01 · Structural

Resting heart rate and all-cause/CV mortality: meta-analysis

Zhang D et al. · 2016 · CMAJ, 2016

TIER 1

D-01 · Structural

Resting heart rate: dose-response meta-analysis

Aune D et al. · 2017 · Nutr Metab Cardiovasc Dis, 2017

TIER 1

D-01 · Structural

Blood pressure variability and cardiovascular disease: meta-analysis

Stevens SL et al. · 2016 · BMJ, 2016

TIER 3

D-01 · Structural

Composite physiological dysregulation as mortality predictor

Arbeev KG et al. · 2020 · Frontiers Public Health, 2020

TIER 3

D-01 · Structural

Short sleep and insomnia associated with accelerated epigenetic age

Kusters CDJ et al. · 2023 · Psychosomatic Medicine, 2023

TIER 3

D-01 · Structural

Sleep traits causally affect epigenetic age acceleration

Mendelian randomization study · 2024 · Scientific Reports, 2024

TIER 3

D-01 · Structural

Imbalanced sleep increases mortality risk by 14–34%

Ungvari Z et al. · 2025 · GeroScience, 2025

TIER 3

D-01 · Structural

Sleep regularity is a stronger mortality predictor than duration

Windred DP et al. · 2024 · Sleep, 2024

TIER 1

D-01 · Structural

Periodontal disease and CV/all-cause mortality: meta-analysis

Guo X et al. · 2023 · PLOS ONE, 2023

TIER 3

D-01 · Structural

Periodontal disease, systemic inflammation, and CV risk

Carrizales-Sepulveda EF et al. · 2018 · Heart Lung Circ, 2018

TIER 3

D-01 · Structural

ECM: structure, composition, biological functions, diseases, and therapeutic targets

Kamal KM et al. · 2026 · Molecular Biomedicine, 2026

TIER 3

D-01 · Structural

Remodeling and homeostasis of the ECM: implications for fibrosis and cancer

Cox TR, Erler JT. · 2011 · Disease Models Mechanisms, 2011

TIER 3

D-01 · Structural

HBOT increases telomere length and decreases immunosenescence

Hachmo Y et al. · 2020 · Aging, 2020

TIER 3

D-01 · Structural

Ozone therapy: pharmacodynamics, research, and clinical utility

Smith NL et al. · 2017 · Medical Gas Research, 2017

TIER 3

D-01 · Structural

Ozone treatment as integrative medicine: evidence-and-gap map

Serra MEG et al. · 2023 · Frontiers Public Health, 2023

TIER 3

D-01 · Structural

EBOO: controlled trial in peripheral artery disease

Di Paolo N, Bocci V et al. · 2005 · Int J Artif Organs, 2005

TIER 3

D-01 · Structural

Scientific and Medical Aspects of Ozone Therapy: State of the Art

Bocci VA. · 2006 · Arch Med Res, 2006

TIER 1

D-01 · Structural

Ozone major autohemotherapy in chronic fatigue (Univ. Bonn Dissertation)

Müller WJ. · 2007 · Univ. Bonn, 2007

What This Evidence Base Claims — And What it Does Not

A structured library is only credible when its limitations are surfaced as explicitly as its strengths. The framework names them on purpose.

No claim of clinical certainty

Evidence supports a structured risk read. It does not certify outcome and does not constitute diagnosis.

Evidence is dynamic

The library is reviewed on a defined cadence. Sources can be retired, demoted, or replaced as the literature evolves.

Tiering is transparent

Every reference is tier-classified by methodology. The framework does not promote weak studies into strong evidence.

Bias is acknowledged

Selection follows institutional protocol but is not blinded. Limitations are surfaced, not hidden.

See Where This Evidence Operates

The library is not the framework. It is the calibration source underneath it. The framework defines how the references resolve into a single governance instrument.

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