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Aging increases the risk of various diseases. The main goal of aging research is to find therapies that attenuate aging and alleviate aging-related diseases. In this study, we screened a natural product library for geroprotective compounds using Werner syndrome (WS) human mesenchymal stem cells (hMSCs), a premature aging model that we recently established. Ten candidate compounds were identified and quercetin was investigated in detail due to its leading effects. Mechanistic studies revealed that quercetin alleviated senescence via the enhancement of cell proliferation and restoration of heterochromatin architecture in WS hMSCs. RNA-sequencing analysis revealed the transcriptional commonalities and differences in the geroprotective effects by quercetin and Vitamin C. Besides WS hMSCs, quercetin also attenuated cellular senescence in Hutchinson-Gilford progeria syndrome (HGPS) and physiological-aging hMSCs. Taken together, our study identifies quercetin as a geroprotective agent against accelerated and natural aging in hMSCs, providing a potential therapeutic intervention for treating age-associated disorders.

Cockayne syndrome (CS) is a rare autosomal recessive inherited disorder characterized by a variety of clinical features, including increased sensitivity to sunlight, progressive neurological abnormalities, and the appearance of premature aging. However, the pathogenesis of CS remains unclear due to the limitations of current disease models. Here, we generate integration-free induced pluripotent stem cells (iPSCs) from fibroblasts from a CS patient bearing mutations in CSB/ERCC6 gene and further derive isogenic genecorrected CS-iPSCs (GC-iPSCs) using the CRISPR/Cas9 system. CS-associated phenotypic defects are recapitulated in CS-iPSC-derived mesenchymal stem cells (MSCs) and neural stem cells (NSCs), both of which display increased susceptibility to DNA damage stress. Premature aging defects in CS-MSCs are rescued by the targeted correction of mutant ERCC6. We next map the transcriptomic landscapes in CS-iPSCs and GC-iPSCs and their somatic stem cell derivatives (MSCs and

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Enterovirus 68 (EV-D68) is associated with respiratory diseases, such as acute upper respiratory tract infections (URTIs), lower respiratory tract infections (LRTIs), pneumonia, neurological diseases, and acute flaccid myelitis (AFM). In recent years, there have been global outbreaks of EV-D68 epidemics. However, there is no effective vaccine against EV-D68, and the understanding of the seroprevalence characteristics of EV-D68 is limited. To evaluate the epidemiological features of this emerging infection in mainland China, serum samples from 20 pairs of pregnant women and their neonates, 405 infants and children (ages 1 month–15 years), and 50 adults were collected to measure EV-D68 neutralizing antibodies (NtAbs). The results showed that the geometric mean titers (GMTs) of pregnant women and their neonates were 168 (95%CI: 93.6–301.7) and 162.3 (95%CI: 89.9–293.1), respectively. The seroprevalence rate of EV-D68 antibodies was negatively correlated with age in 1-month-old to 12-month-old infants (84% for 1-month-old infants vs 10% for 1-year-old infants), whereas it was positively correlated with age for 1-year-old to 15-year-old children (10% for 1-year-old children vs 92% for 15-year-old children). This study evaluated maternal antibodies against EV-D68 in neonates. Our results showed that if mothers had high levels of anti-EV-D68 NtAbs, the NtAbs titers in their neonates were also high. The GMTs and seroprevalence rates of each age group indicated that EV-D68 infection was very common in China. Periodical EV-D68 seroprevalence surveys and vaccination campaigns should be the top priority for preventing EV-D68 infection.