Michael West proposed a mechanism by which senescent cells may alter tissue elasticity
Michael West proposed a mechanism by which senescent cells may alter tissue elasticity
On September 2, aging researcher Michael West presented a hypothesis in a detailed post: substances secreted by a senescent cell may act through the environment between cells to alter tissue elasticity.
When West was young, his father asked him to place his hand beside his father's hand and pinched the skin on the back of each hand. The fold remained raised on his father's hand but quickly flattened on West's. This experience led West to ask how the state of individual cells changes a tissue.
A senescent cell stops dividing. SASP is the collection of substances secreted by such a cell. In graduate school, West cultured young skin fibroblasts, which are connective tissue cells, until they stopped dividing. He then labeled the proteins they synthesized to identify differences.
West writes that he detected proteases, which are enzymes that break down proteins, in these cells. Proteases can degrade proteins in the extracellular matrix, the environment between cells that helps tissue maintain its structure and function. He described the following sequence: plasminogen activators activate plasmin, which then activates metalloproteinases, another group of protein-degrading enzymes. These enzymes can degrade elastin, a matrix protein that gives tissue its elasticity.
West therefore connects cellular secretion with a tissue property through a specific mechanism. The enzymes may degrade elastin, and the resulting loss of elastin alters elasticity. In this account, the case of a 16-year-old girl with cutis laxa, an inherited disorder of elastic fibers, illustrates how strongly defects in these fibers can alter tissue.
A Nature Aging commentary on the aging matrix describes a feedback loop. An altered tissue environment may sustain senescent cells, which in turn remodel the matrix. West's hypothesis identifies one possible part of this loop: substances secreted by cells may promote elastin degradation through proteases.
A review of skin aging supports the broader mechanism: SASP may sustain inflammation and extracellular matrix degradation. West connects this mechanism to the sequence from proteases to elastin that he identified earlier in his career.
West's hypothesis can be tested in tissue by comparing SASP composition, protease activity, matrix condition, and the properties of the tissue itself.