(f) Representative images of SA-?-gal-positive cells in cultures exhibiting <5% SNS, 15% SNS and 30% SNS. pathway. We statement the inhibition of the JAK-STAT pathway with baricitinib, a Food and Drug Administration-approved JAK1/2 inhibitor, restored cellular homeostasis, delayed senescence and decreased proinflammatory markers in HGPS cells. Our ex lover vivo data using human being cell models show the overactivation of JAK-STAT signaling mediates premature senescence and that the inhibition of this pathway could display promise for the AQ-13 dihydrochloride treatment of HGPS and age-related pathologies. gene . In the majority of HGPS cases, a single de novo mutation (LMNA 1824C >T, G608G) activates a cryptic splicing site, causing the production of a truncated prelamin A protein having a 50 amino acid deletion called progerin. Progerin lacks the cleavage site for zinc-metalloproteinase (ZMPSTE24) and therefore remains farnesylated, causing modified gene manifestation, DNA damage, mitochondrial dysfunction, defective proteostasis and oxidative stress which cause cells to enter premature senescence . Among all the characteristics that characterize HGPS individuals, we focused on the four conditions typically acknowledged, namely, vascular disease, AQ-13 dihydrochloride arthritis, lipodystrophy, and alopecia. These pathologies are not specific to HGPS, as these conditions also develop in individuals suffering from additional progeroid syndromes, such as in instances of mandibuloacral dysplasia (MAD), restrictive dermopathy (RD), and Malouf syndrome [5,6]. To examine whether these four conditions might share common defective molecular mechanisms, we investigated the literature to find the occurrence of these pathologies in different combinations in individuals other than HGPS patients. Indeed, the incidence of these four pathologies is not restricted to HGPS; for instance, vascular disease and alopecia are observed in individuals with severe androgenetic alopecia (AGA)  or cerebral autosomal recessive arteriopathy with subcortical infarct and leukoencephalopathy (CARASIL) . Atherosclerosis and loss of subcutaneous excess fat happen in congenital generalized lipodystrophy and in individuals with HIV-associated lipodystrophy syndrome [9,10]. Rheumatoid arthritis and alopecia or lipodystrophy are observed in individuals with juvenile dermatomyositis . Hence, these four conditions also impact normal seniors individuals albeit hardly ever all together. The cooccurrence of these four age-related diseases prompted us to investigate whether these pathologies could result from a DRIP78 shared imbalanced signaling pathway or converging pathways. Several studies on HGPS have reported alterations in different signaling pathways, including the mammalian target of rapamycin (mTOR) , retinoblastoma protein (pRb) , nuclear element kappa B (NF-B)  and nuclear element erythroid 2Crelated element 2 (Nrf2) [15,16]. However, how these pathways initiate the development of HGPS and particularly these four pathologies remains unfamiliar. To gain additional insight into HGPS pathogenesis, we tested our hypothesis that converging signaling pathway(s) might underlie the development of the four conditions, namely, vascular disease, arthritis, lipodystrophy, and alopecia by carrying out a text mining analysis of scientific literature and databases to identify genes reported to be altered in each of these four unique pathologies. This text mining approach recognized a unique set of 17 genes that were found to be altered in all four pathologies. Analyses of the 17 genes using bioinformatics showed that all 17 entities were AQ-13 dihydrochloride interconnected and therefore belonged to converging signaling pathways. Furthermore, 14, out of these 17 genes encoded for proinflammatory factors that are known goals of Janus kinase (JAK)Csignal transducer and activator of transcription (STAT) signaling. Using an former mate cell-based maturing model vivo, we demonstrated the fact that 17 genes, like the 14 genes encoding proinflammatory goals and elements of JAK-STAT signaling, were changed in HGPS and in regular cells during replicative senescence and during DNA harm induced senescence. Our.