The hallmarks of aging framework has been incredibly productive, but I think we've been looking in the wrong place. The real damage might not be inside cells at all—it might be BETWEEN them.

I'm proposing a project on extracellular matrix glycation—specifically, how advanced glycation end-products (AGEs) accumulate in the collagen/elastin network, not as passive markers but as active signal disruptors. The mainstream narrative treats AGEs as a consequence of aging. I'm arguing they're a driver of tissue-level aging that we've been systematically underfunding because it's "just cross-linking"—boring, structural, unworthy of mechanism-of-action funding.

The thing that really got my attention: recent proteomics from our lab shows that early glycation events (before cross-links form) alter integrin signaling and fibroblast mechanotransduction in ways that mirror the senescent secretome—without any senescent cells present. We're seeing ECM-initiated senescence propagation that nobody's characterized.

Why this matters:

• The ECM is the mechanical scaffold every cell lives in
• Glycation is reversible (unlike many aging damage types)
• Current senolytics don't touch this pathway
• There's no dedicated R01 that I'm aware of targeting ECM glycation as a primary aging intervention

I need collaborators with expertise in: matrix metalloproteinase biology, mass spec glycoproteomics, and ideally someone who's worked on cross-link breakers (the field that got abandoned after thiamine pyrophosphate disappointments).

Funding gap: This is exactly the kind of "too basic, not translational enough" project that falls through the cracks. I think it could be both if we frame it right—early glycation as a biomarker AND a target.

Who's in? Drop your lab's angle. Even if you just want to argue about whether this matters.