Links Between Inflammatory Senescent Cell Secretions and Markers of Inflammation are Lacking

Senescent cells contribute significantly to the chronic inflammation of aging, via their secretions, the senescence-associated secretory phenotype. A comparatively small number of such cells produces an outsized effect both on nearby cell behavior, and behavior throughout the body, and this accelerates the progression of age-related degeneration. Yet this increase in inflammatory signaling due to the presence of senescent cells takes place without producing well-correlated effects on the established inflammatory marker assays measured in blood samples. This is one of the aspects of senescent cell biology that complicates the production of useful, low-impact tests to measure senescent cell burden in an individual.

Is there any established correlation between Senescence-Associated Secretory Phenotype (SASP) or senescent cell burden on one side and the measured C-reactive protein level or any other routinely measured inflammatory marker in an individual on the other side? Unfortunately not. Scientists first started asking this question around the time of the first proof-of-concept of the value of destroying senescent cells, and initially hoped it would be a straightforward matter of simply measuring the levels of various SASP factors directly in the blood. While none of the components of the SASP are common blood tests like C-reactive protein, some commercial blood-testing labs do test for specific proteins that are part of the SASP, including interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α).

Somewhat surprisingly, however, things did not turn out to be quite that simple, for reasons that aren't entirely clear. Perhaps the SASP factors concentrate too locally around senescent cells to be easily picked up in the blood. Or perhaps it relates to the fact that none of the individual proteins and lipid derivatives released from senescent cells as part of the SASP are actually unique to senescent cells. Instead, all of the proteins that make up the witches' brew of proteins that is the SASP are are repurposed growth factors, protein-degrading enzymes, and above all inflammatory signaling molecules that also produced by non-senescent cells in the body to do things like break down damaged muscle, recruit immune cells, remodel injured tissue, and so on. This might mean that the signal from true SASP factors is swamped out by the fact that those same factors are produced at relatively high levels in an aged person's body for other reasons, in response to their high burden of aging damage.

And precisely because each individual SASP factor is produced by non-senescent cells for other purposes entirely, no one marker can be used as a reliable index of SASP production: the level of any given factor always reflects a mixture of SASP-related production and production for entirely different reasons. As such, measuring just one or even a few SASP factors in the blood and correlating that to the actual number of senescent cells in your body or the level of SASP they're producing is likely a fool's errand from the start.


Comment Submission

Post a comment; thoughtful, considered opinions are valued. New comments can be edited for a few minutes following submission. Comments incorporating ad hominem attacks, advertising, and other forms of inappropriate behavior are likely to be deleted.

Note that there is a comment feed for those who like to keep up with conversations.