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Acarbose improves health and lifespan in aging HET3 mice
Acarbose inhibits alpha-glucosidase, reducing the rate of digestion of polysaccharides and blunding the post-prandial rise in serum glucose. Previous work by Dr. Miller and colleagues demonstrated that treatment with acarbose increases lifespan. This follow-up study confirms and extends that work, testing 3 different doses of acarbose in male and female HET3 mice. Acarbose extended lifespan at all 3 doses, and did so in males to a much greater extent than in females. Effects on lifespan and body weight at different doses are shown in the Figure (females (a) and (c); males (b) and (d)). The two higher doses extended lifespan by 16-17% in males but only 4-5% in females...
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Recent Work by NORCH Investigators
Childhood undernutrition and growth impairment remain substantial burdens in Sub-Saharan Africa. Environmental enteric dysfunction (EED), a subclinical condition associated with inflammation and malabsorpition in the small intestine, is associated with growth failure. As several studies have demonstrated that individuals with low weight in early childhood are at risk for cardiometabolic disease later in life, NORCH Associate Director Dr. Christopher P. Duggan, NORCH member Dr. Wafaie Fawzi, and others recently investigated whether EED in infancy is associated with cardiovascular risk measures in mid-childhood. Anti-flagellin IgA is a marker for EED and is significantly higher in Tanzanian infants compared to infants in Boston. Drs. Duggan, Fawzie, et al. demonstrated that flagellin IgA at 6 weeks of age is associated with both systolic and diastolic blood pressure in mid-childhood
Activation of IRF1 in Human Adipocytes Leads to Phenotypes Associated
with Metabolic Disease
Chronic inflammation is thought to contribute to obesity-related insulin resistance. In obesity, adipocytes are an important source of inflammatory cytokines, but the mechanisms of adipose inflammation in obesity remain unclear. To determine transcriptional regulators of adipose inflammation, Cowan and colleagues compared transcriptional profiles of primary human adipocytes from obese donors with those from in vitro-derived adipocytes that were genetically identical to the primary adipocytes.
Recent Work by NORCH Investigators
With support from a NORCH Pilot and Feasibility Grant, Dr. Lauren Feichtner and others recently reported that gestational weight gain affects the composition and diversity of the infant gut microbiome. Using data and infant fecal samples from 84 infant-mother pairs, four distinct microbiota profiles were identified: Bifidobacterium-dominant, Enterobacter/Veillonella-dominant, Bacteroides-dominant, and Escherichia-dominant. Infants whose mothers had more weight gain during pregnancy were less likely to have a Bacteroides-dominant profile (risk ratio 0.83 [95% CI 0.71-0.96] per 1kg of gestational weight gain). Further, a larger amount of gestational weight gain predicted lower bacterial diversity.
Adipose Tissue-Derived miRNAs Regulate Gene Expression in Other Tissues
MicroRNAs (miRNAs) are small, non-coding RNAs that negatively regulate translation
and thereby contribute to the regulation of metabolic processes. Dr. Kahn and others
recently demonstrated in Nature that adipose tissue is an important source of
circulating miRNAs. Mice with an adipose-tissue-specific knockout of the miRNA
processing enzyme Dicer (ADicerKO) demonstrated substantial reductions in levels of
circulating miRNAs, and fat transplant from wild type animals largely restored miRNA levels.