More on the SASP Atlas, a Basis for Biomarkers of Aging

In the publicity materials here, researchers discuss the recently published SASP Atlas, a fairly comprehensive map of the molecules secreted by senescent cells - the senescence-associated secretory phenotype (SASP). Cells become senescent at the end of their replicative lifespan, but also in response to wounding, DNA damage, a toxic environment, or the signals of senescent neighbors. Senescence is transient, in the sense that these cells should self-destruct or be destroyed by the immune system shortly after their creation. Unfortunately these processes become inefficient with age, leading to rising numbers of senescent cells throughout the body. When senescent cells are present in sizable numbers for long periods of time, the SASP becomes very harmful. It disrupts tissue function and produces chronic inflammation. It is an important contributing cause of aging.

Senescent cells, which stop dividing under stress, are long-recognized drivers of multiple diseases of aging. Mouse studies have shown that targeted removal of these cells and the inflammatory factors they secrete, known as the senescence-associated secretory phenotype (SASP), has beneficial results on multiple organ systems and functions. Success in the laboratory has given rise to companies and research projects aimed at developing either senolytics, drugs that clear senescent cells, or senomorphics, drugs that suppress the SASP. But drug development and clinical utilization require simple, reliable biomarkers to assess the abundance of senescent cells in human tissues.

Researchers have now extensively profiled the SASP of human cells and have generated a curated database available for use in the field, the SASP Atlas. "The stage is now set for the development of clinically-relevant biomarkers of aging. This will speed efforts to get safe and effective drugs into the clinic and, in the long term, could enable physicians to give patients a clear read-out of how well, or poorly, their various tissues and organs are aging. The complexity of the SASP, which is typically monitored by a few dozen secreted proteins, has been greatly underappreciated, and a small set of factors cannot explain the diverse phenotypes senescence produces in vivo."

The SASP Atlas as a comprehensive proteomic database of soluble and exosome SASP factors originating from multiple senescence inducers and cell types. Each profile consists of hundreds of largely distinct proteins, but also includes a 'core' subset of proteins elevated in all SASPs. "For the first time we have the capability of measuring the burden of senescent cells in vivo and making educated guesses on how they became senescent and how neighboring cells are being affected."


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