The Polycentric Aging Framework (PAF) is an original framework developed by Michał Bartoszewicz to organise interconnected mechanisms of aging and the constraints on potential rejuvenation.
The framework was described in a review published in Aging on 9 October 2026. Michał Bartoszewicz is the creator of the model. Michał Bartoszewicz and Mariusz Niemczyk are the authors of the publication.
PAF in one minute
Aging need not have a single cause or a single clock. PAF describes several layers of constraints that can develop in parallel and reinforce one another. Improving one mechanism may leave other barriers in place.
The central hypothesis assigns epigenetic regulation a dominant, but not exclusive, role in limiting human lifespan. This is a proposal requiring further testing, not proof that a rejuvenation treatment works.
Three layers of constraints
Epigenetic regulation
Proposed dominant layer in humans
Regulation of gene activity and maintenance of cellular identity.
Genetic and physical damage
Constraints that are not removed simply by restoring regulation.
Proteostasis and cellular waste
Protein quality and clearance of damaged macromolecules and organelles.
The layers interact. Changing one does not automatically remove the other constraints.
Connections between layers: mitochondria link metabolism, signalling and damage; telomeres act as checkpoints; stem cells and their niches provide an interface for regeneration. Cellular senescence and SASP may act as effectors and amplifiers. Systemic signalling provides context. These elements are not treated as equivalent, independent clocks.
What does PAF contribute?
PAF connects aging mechanisms within a hierarchical structure of constraints. It asks not only whether an intervention improves a biomarker, but which barrier it changes, which barriers remain and whether the change improves organismal function.
Evidence, interpretation and predictions
- Evidence: findings from research on aging mechanisms reviewed and cited in the paper. Their strength depends on the experimental model, measurements and study design.
- PAF interpretation: the proposed relationships between these findings and the hypothesis of a dominant epigenetic-regulatory layer in humans.
- Predictions: improvement in one layer may expose other constraints; assessing rejuvenation requires molecular measures alongside durable functional benefit and safety.
How can PAF be tested?
Studies should distinguish biomarker changes from functional improvement, compare interventions targeting different layers and assess the durability of outcomes. The proposed dominance of epigenetic regulation would need revision if other constraints explained aging better, or if restoring regulation failed to produce predicted functional benefits when other barriers were controlled.
A lower epigenetic clock estimate alone does not demonstrate whole-organism rejuvenation. PAF is not a treatment protocol or a recommendation to use drugs, hormones or supplements.
Model creator and publication history
Michał Bartoszewicz originated the Polycentric Parallel Aging Hypothesis, subsequently developed into the Polycentric Aging Framework. As stated in the author contributions, he developed the conceptual framework, reviewed the literature and drafted the manuscript. Mariusz Niemczyk proposed the literature review, contributed to manuscript planning and provided academic supervision and manuscript revision.
Source and citation
Bartoszewicz M, Niemczyk M. The polycentric aging framework: epigenetic regulation as a dominant lifespan-limiting center in human aging. Aging. 2026;18:1365–1423. DOI: 10.18632/aging.206426. Published: 9 October 2026.
This page is a plain-language introduction. Read the full publication for the detailed argument, limitations, references and author contributions.
Further reading
Michał Bartoszewicz — model creator · A guide to aging research · Why an epigenetic clock is not enough