Nunes, Allancer

Abstract The Midwest Aging Consortium (MAC) has emerged as a critical collaborative initiative aimed at advancing our understanding of aging and developing strategies to combat the rising prevalence of age-related diseases. Founded in 2019, MAC brings together researchers from various disciplines and institutions across the Midwestern United States to foster interdisciplinary geroscience research. This report summarizes the highlights of the Fourth Annual Symposium of MAC, which was held at Iowa State University in May 2023. The symposium featured presentations on a wide array of topics, including studies on slow-aging animals, cellular senescence and senotherapeutics, the role of the immune system in aging, metabolic changes in aging, neuronal health in aging, and biomarkers for measuring the aging process. Speakers shared findings from studies involving a variety of animals, ranging from commonly used species such as mice, rats, worms, yeast, and fruit flies, to less-common ones like naked mole-rats, painted turtles, and rotifers. MAC continues to emphasize the importance of supporting emerging researchers and fostering a collaborative environment, positioning itself as a leader in aging research. This symposium not only showcased the current state of aging biology research but also highlighted the consortium’s role in training the next generation of scientists dedicated to improving the healthspan and well-being of the aging population.

Cellular senescence represents one of the major risk factors for chronic liver disease and contributes to morbidity, mortality, and increased healthcare spending. A relevant strategy for understanding the role of senescent cells in liver pathogenesis is to use genetic or pharmacological strategies to eliminate senescent cells. The combination of the senolytic drugs, Dasatinib and Quercetin (D+Q), effectively reduces senescent cell burden in multiple tissues, extending both healthspan and lifespan in mice, and alliviating obesity and age‐associated hepatic steatosis. The aim of this study was to investigate effects of D+Q treatment on livers of young and old female mice. A total of 40 mice, 20 young females (3‐months) and 20 old females (18‐months), was divided into 4 groups: Young (Y) mice treated with either D+Q or placebo and old (O) mice treated with D+Q or placebo. The treatment was performed for 3 consecutive days every 2 weeks over 10 weeks. Comparative analysis of hepatic miRNAs indicated that D+Q treatment significantly decreased levels of senescence‐specific miR‐126 expression in livers of old mice treated with D+Q compared to vehicle‐treated old mice (p=0.025), As expected, there was no effect of D+Q treatment in young animals. Analysis of miR‐126 target genes indicated that PI3K gene expression was significantly increased in response to D+Q treatment (p=0.003). Additionally, Akt1 and mTOR mRNA levels were increased in D+Q‐treated mice (p=0.008 and p=0.02, respectively). In summary, our data suggest that the mechanism of PI3K signaling pathway activation upon elimination of senescent cells by treatment with D+Q is mediated through downregulation of senescence‐specific miR‐126. Support or Funding Information This work is supported by National Institutes of Health (NIH) (R56AG061414, R15AG059190 and R03AG059846)