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

In eukaryotes, cellular senescence is a highly conserved stress response elicited by acute or chronic damage signals. In humans, senescent cells accumulate in multiple tissues 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). Melatonin is a methoxyindole synthesized and secreted mainly by the pineal gland during night under normal light/dark conditions. The endogenous rhythm of melatonin secretion is governed by the suprachiasmatic nuclei and entrained to the light/dark cycle. Light is able to either suppress or synchronize melatonin production in accordance with the light schedule. The nycthohemeral rhythm of this hormone can be evaluated by repeated measurement of plasma or saliva melatonin or urine sulfatoxymelatonin, the main hepatic metabolite. The primary physiological function of melatonin, whose secretion adjusts to night length, is to convey information concerning the daily cycle of light and darkness to body structures. However, there is a lack of insights into the biological capacity of melatonin in modulation of chronological aging and regulation of organismal healthspan. In this study, we aimed to evaluate the anti-aging potential of melatonin, by profiling the influence of melatonin on the transcriptome-wide expression of human stromal cells made senescent by genotoxicity in vitro. Together, this is the first report to determine the possibility of employing melatonin as a source of endogenous rhythm-related molecules in anti-aging pipelines, particularly pharmacological development for future geriatric medicine. Overall design: High-throughput RNA-seq examination of genome-wide transcriptional alterations of human stromal cells that underwent treatment by the chemotherapeutic agent bleomycin and/or exposure to melatonin (recombinant product). Please note that, for melatonin-related investigations, the following samples in GSE264076/PRJNA1100940 samples were re-used/re-analyzed together with the melatonin treatment-related data: SRR28705054 SRX24272271 GSM8209760: CTRL-01 SAMN40982160 SRR28705053 SRX24272272 GSM8209761: CTRL-02 SAMN40982159 SRR28705052 SRX24272273 GSM8209762: CTRL-03 SAMN40982158 SRR28705051 SRX24272274 GSM8209763: BLEO-01 SAMN40982157 SRR28705050 SRX24272275 GSM8209764: BLEO-02 SAMN40982156 SRR28705049 SRX24272276 GSM8209765: BLEO-03 SAMN40982155