Cellular senescence: zombie cells and matrix metalloproteinases

In a recent Quartz piece called The first drugs designed to fight aging are ready for human testing, the journalist W. Harry Fortuna provides an excellent and pictorial description of the important biological process, cellular senescence:

Senolytics target a known mechanism of aging, cell senescence. Normally, cells die a “complete” death known as apoptosis. Senescence is when a cell sort of zombifies: After senescence, the cell is essentially empty, and doesn’t replicate or do anything useful. What it does do, is hang around and secrete inflammatory chemicals which disrupt the functions of healthy cells adjacent to it. Why exactly some cells enter senescence instead of apoptosis is not fully understood, but one theory is that senescence is a defensive response that prevents a cell from becoming tumorous: it halts unchecked growth, stopping a cell from becoming cancer.

One thing these zombie cells do is to excrete protein digesting enzymes called matrix metalloproteinases(MMs) in large amounts, see references in the classic paper Four faces of cellular senescence by Rodier and Campisi.

Matrix metalloproteinases come in different flavours  and they are capable to digest different kinds of extracellular matrix proteins. For instance MMP-1 is called collagenase and can break down, guess what, collagen, the main structural protein, protein in our bodies, that also happens to be the most abundant protein due to its function. The MMs’ digesting capability is essential for tissue remodelling and organogenesis during development and growth and also for normal tissue turnover, the everyday business of replacing, renewing the ECM.

But in  zombie cells, the excess amount of MMs are creating a hostile tissue environment for normal functioning cells and form part of the proinflammatory secretome of senesecent cells that might contribute to the tissue level aging process.

Targeting senescent cells is a very promising and very popular treatment strategy these days and different startups raised significant amount of funding to fight senescent cells in different diseases, like osteoarthritis or chronic kideny disease.

One of the age related super stories we report back is on these frail cells. In this story AgeCurve users can learn about their matrix metalloproteinase levels compared to their age group suggesting accelerated, normal or decelerated aging status concerning this molecular hallmark of aging. We particularly report on MMP-9, which is detected in >85% of our samples.