Live·Open questions in longevity research
Research perspectives

Research directions

Topology of age-related changes

Study the spatial organisation of life: chromatin folding, cell arrangement and tissue architecture. Test how changes in shape and connections affect function.

Interconnected coloured routes form an abstract organism, in screen-printed wayfinding style.
Conceptual illustration

Levels of spatial organisation

  1. Chromatin folding. Packing density and contacts between genomic regions change. Test how these rearrangements relate to gene expression during ageing.

  2. Cell arrangement. Cell neighbours, polarity and contact with the supporting environment matter. Spatial measurements connect cell state with its location in a tissue.

  3. Tissue architecture. Vessel arrangement and extracellular structure can constrain supply, signalling and repair. Test these relationships by changing tissue structure.

The spatial organisation of cells and tissues

Topology concerns the arrangement and connectivity of elements; geometry adds their shape and distances. Chromatin folding affects gene accessibility and expression. Cells, extracellular material and vessels define tissue architecture. The research idea is to connect age-related changes in this organisation to functional decline and test whether restoring it helps.

What to investigate

  1. Combine chromatin organisation and gene-expression measurements in the same cell types across ages.

  2. Map cells, vessels and extracellular material while preserving measurement coordinates.

  3. Change a specific element of spatial organisation and measure cell or tissue function.

Evidence to build on

A 2016 study examined the chromatin-associated protein HMGB2. In senescent cells it helped maintain expression of genes for secreted signalling factors. Its loss allowed repressive chromatin to spread into these loci and reduced their expression, linking genome organisation to cell function.

What remains unresolved

A chromatin change in a cell model establishes a specific link with gene expression. Tissue restoration and lifespan effects require tissue-level and organism-level experiments.

The next useful experiment

Modify one regulator of chromatin folding and measure spatial contacts, gene expression and cell function. Then test whether the result holds in tissue.

Proposed experiments

The wider strategy

This section develops the study of biological organisation: from shape and connections to causes of age-related change and ways to restore function.

The Death-Fighting Spectrum presentation