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ZENODO
Part of book or chapter of book . 2026
License: CC BY
Data sources: ZENODO
ZENODO
Preprint . 2026
License: CC BY
Data sources: Datacite
ZENODO
Preprint . 2026
License: CC BY
Data sources: Datacite
ZENODO
Preprint . 2026
License: CC BY
Data sources: Datacite
ZENODO
Part of book or chapter of book . 2026
License: CC BY
Data sources: Datacite
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Aging as Meta-Disease: A Comprehensive Framework Integrating Set Theory with Cellular Senescence as Causal Nexus

Authors: Csoka, Antonei B.; Stambler, Ilia; West, Michael D.; Heinbockel, Thomas; Bhowmik, Debsindhu; Herbig, Utz; Stair, Susan E.;

Aging as Meta-Disease: A Comprehensive Framework Integrating Set Theory with Cellular Senescence as Causal Nexus

Abstract

Whether aging should be classified as a disease remains contentious. We propose a conceptual synthesis: aging is a meta-disease - a universal, upstream pathological condition that gives rise to the full spectrum of age-related disorders, as well as the structural and cosmetic changes historically dismissed as “normal aging.” This framework reflects a Hegelian dialectic, in which the traditional thesis (aging is a natural process) and the antithesis (aging is a disease) are integrated into a higher-order synthesis. This synthesis preserves the valid insights of each while overcoming their limitations: aging is not a discrete disease, yet it is mechanistically central to disease emergence. It is thus the generative causal architecture from which age-related diseases arise - not itself a subset within pathology, but the ontological ground that gives rise to it. This reconceptualization rests on two core pillars. First, a set-theoretic nosology: aging defines the universal set A. Each age-related disease family constitutes a proper subset within A (e.g. cardiovascular disease V ⊂ A, neurodegeneration N ⊂ A). Cosmetic (K) and structural (T) changes comprise partially overlapping subsets (K ⊂ A, T ⊂ A). This formalism enables a precise explanation of comorbidity, multimorbidity, and the structural and cosmetic overlap of age-related conditions. Second, cellular senescence is the causal nexus: diverse molecular lesions converge on senescence, defined by irreversible proliferative arrest and activation of the senescence-associated secretory phenotype, and characterized by a distinctive multi-omic signature we term the senescome. Senescence functions as a pivotal biological switch - an “event horizon” - beyond which transient molecular insults are converted into chronic, system-wide dysfunction. Through these mechanisms, senescence is the causal generating set (S) inside A that initiates and propagates the various disease subsets. This meta-disease framework situates geroscience within a causal ontology, defining aging as the generative source of pathology. As the antecedent ground of disease, aging thus emerges as the logical primary therapeutic target. Integrating these concepts clarifies terminology and provides formal coherence to International Classification of Diseases extension code XT9T (“Ageing-related”) and stem code MG2A (“Ageing associated decline in intrinsic capacity”). It also provides practical levers for advancing biomarker portfolios, composite clinical trial endpoints, mechanism-based therapeutic development, regulatory frameworks, and reimbursement models for geroprotective interventions. We conclude by proposing a policy roadmap for translating the meta-disease paradigm into coordinated clinical, regulatory, and public health action, and by examining its implications for the purpose and future of medicine.

This is a preprint of a chapter in the forthcoming edited volume Healthy Longevity: Policies and Practices; Volume 23 of the book series Healthy Ageing and Longevity (Springer Nature), to be published in 2026.

Keywords

Aging, Meta-Disease, ICD-11, Longevity, Hegelian Dialectic, Set Theory, Event Horizon, Longevity Dividend, Geroscience, Cellular Senescence, Causal Nexus

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
0
Average
Average
Average