In the aging somatic landscape, cells are locked in a quiet tug-of-war between two strategies for managing extra centrosomes.

On one side sits the Clustering Fidelity Hypothesis, which frames centrosome clustering as a robust evolutionary safety switch. The idea is that it prevents multipolar mitosis, effectively shielding genome stability from numerical aberrations. Proponents suggest this is why we don’t suffer immediate mitotic catastrophe the moment our centrosomes start duplicating in our 50s.

Then there’s the Persistent Mutational Sink Hypothesis. This view argues that clustering is little more than a cosmetic bandage. It masks the mechanical strain on the spindle, creating subtle, recurring kinetochore attachment errors that slip right past the spindle assembly checkpoint. Here, we aren't preventing instability; we’re just normalizing it.

Which side wins? My money is on the Sink.

Look at the transcriptomic profiles of aged somatic cells and you’ll find chronic, low-level activation of p53-mediated DNA damage responses that don't always trigger senescence. This suggests cells are living with a constant, hidden level of chromosomal breakage that clustering doesn't fix—it just keeps the cell cycling long enough to pick up the next mutation.

We’re essentially watching a cellular version of kicking the can down the road. By clustering these extra centrosomes, the cell buys itself a few more divisions, but at the cost of compounding its genetic debt.

If this is right, the implications for aging are massive: our supposed safety mechanisms might be the very things driving the somatic mutational burden that defines late-life decline.

The field is at a crossroads. We need more high-resolution live-imaging data on aged primary human fibroblasts, and we need it yesterday. We’re under-funding the mechanical biology of the aging cell at our own peril. We have the tools—cryo-ET, advanced light-sheet microscopy, single-cell sequencing—but we lack the focused, multi-lab collaboration required to map this dynamic process in vivo.

Are we looking at an inevitable trade-off, or can we modulate the clustering machinery to force these cells into apoptosis before they become the mutational engines of tomorrow? I’m curious to hear from those working on spindle-assembly stabilizers. Are we fixing the engine, or just painting over the rust?