Disease incidences increase with age, but the molecular characteristics of ageing that lead to increased disease susceptibility remain inadequately understood. Here we perform a whole-blood gene expression meta-analysis in 14,983 individuals of European ancestry (including replication) and identify 1,497 genes that are differentially expressed with chronological age. The age-associated genes do not harbor more age-associated CpG-methylation sites than other genes, but are instead enriched for the presence of potentially functional CpG-methylation sites in enhancer and insulator regions that associate with both chronological age and gene expression levels. We further used the gene expression profiles to calculate the ‘transcriptomic age' of an individual, and show that differences between transcriptomic age and chronological age are associated with biological features linked to ageing, such as blood pressure, cholesterol levels, fasting glucose, and body mass index. The transcriptomic prediction model adds biological relevance and complements existing epigenetic prediction models, and can be used by others to calculate transcriptomic age in external cohorts.
Human angiostrongyliasis caused by Angiostrongylus cantonensis, a rat lungworm, has been reported globally. Human infections are acquired by ingestion of raw or undercooked snails or slugs, paratenic hosts such as prawns, or contaminated vegetables that contain the infective larvae of the worm. So far, at least 2827 cases of the disease have been documented worldwide. During the past few years, several outbreaks of human angiostrongyliasis have been reported in mainland China, Taiwan, and the USA. Additionally, sporadic cases in travellers who have returned from endemic areas have been reported. We review the clinical features, diagnosis, and treatment of human angiostrongyliasis, and describe the geographical distribution and prevalence of A cantonensis. Educating the public about the dangers of eating raw or undercooked intermediate and paratenic hosts in endemic areas is essential for the prevention and control of this foodborne zoonotic disease.
Elevated branched-chain amino acids (BCAAs) are associated with obesity and insulin resistance. How long-term dietary BCAAs impact late-life health and lifespan is unknown. Here, we show that when dietary BCAAs are varied against a fixed, isocaloric macronutrient background, long-term exposure to high BCAA diets leads to hyperphagia, obesity and reduced lifespan. These effects are not due to elevated BCAA per se or hepatic mammalian target of rapamycin activation, but instead are due to a shift in the relative quantity of dietary BCAAs and other amino acids, notably tryptophan and threonine. Increasing the ratio of BCAAs to these amino acids results in hyperphagia and is associated with central serotonin depletion. Preventing hyperphagia by calorie restriction or pair-feeding averts the health costs of a high-BCAA diet. Our data highlight a role for amino acid quality in energy balance and show that health costs of chronic high BCAA intakes need not be due to intrinsic toxicity but instead are a consequence of hyperphagia driven by amino acid imbalance.
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