Transcriptomic landscape of human stromal cells upon therapy-induced senescence and/or senotherapeutic intervention with PQQ

In higher eukaryotes, cellular senescence represents a significantly conserved stress response triggered by acute or chronic damage signals. In humans, senescent cells can accumulate in multiple tissues and organs at different rates, from 2- to 20-fold when comparing young (<35 years) to old (>65 years) healthy donors. The pathogenic role of cellular senescence in the vast majority of age-related diseases can be explained by the senescence-associated secretory phenotype (SASP). Pyrroloquinoline quinone (PQQ) is a water-soluble vitamin-like compound exhibiting strong antioxidant capacity, and was first discovered to function as a cofactor for oxidoreductases in bacteria. The effects of PQQ largely rely on its radical-scavenging activity, which has been demonstrated to be 7.4-fold higher than that of vitamin C. However, the specific mechanism underlying its antioxidant function remains largely unclear. Although PQQ cannot be synthesized in mammals, it is available in foods such as milk, vegetables and meat, making it an ideal agent for alleviating oxidative stress-induced diseases. The purpose of this study was to investigate whether PQQ exerts certain effects on cellular senescence-associated phenotypes, specifically the SASP. We profiled the influence of PQQ on the transcriptome-wide expression of human stromal cells that were made senescent by genotoxicity in vitro. Together, this is the first report to determine the possibility of using PQQ as a source of antioxidant senomorphics for senescence-modulation and explore its potential in anti-aging pipelines, particularly pharmacological development for future geriatric medicine.