Age-dependent changes in the gut microbiota and serum metabolome correlate with renal function and human aging.

Human aging is invariably accompanied by a decline in renal function, a process potentially exacerbated by uremic toxins originating from gut microbes. Based on a registered household Chinese Guangxi longevity cohort (n = 151), we conducted comprehensive profiling of the gut microbiota and serum metabolome of individuals from 22 to 111 years of age and validated the findings in two independent East Asian aging cohorts (Japan aging cohort n = 330, Yunnan aging cohort n = 80), identifying unique age-dependent differences in the microbiota and serum metabolome. We discovered that the influence of the gut microbiota on serum metabolites intensifies with advancing age. Furthermore, mediation analyses unveiled putative causal relationships between the gut microbiota (Escherichia coli, Odoribacter splanchnicus, and Desulfovibrio piger) and serum metabolite markers related to impaired renal function (p-cresol, N-phenylacetylglutamine, 2-oxindole, and 4-aminohippuric acid) and aging. The fecal microbiota transplantation experiment demonstrated that the feces of elderly individuals could influence markers related to impaired renal function in the serum. Our findings reveal novel links between age-dependent alterations in the gut microbiota and serum metabolite markers of impaired renal function, providing novel insights into the effects of microbiota-metabolite interplay on renal function and healthy aging.

[Application of High Resolution Melting Curve Analysis in Detection of SLC4A1 Gene Mutation in Patients with Hereditary Spherocytosis].

OBJECTIVE: To investigate the feasibility and clinical significance of high resolution melting(HRM) curve analysis to detect SLC4A1 gene D38A and K56E mutations in the patients with hereditary spherocytosis(HS). METHODS: Peripheral blood was collected from 23 cases of HS for routine tests and their genomic DNA was extracted by routine technique. Specific primers of mutation sites D38A and K56E of SLC4A1 gene were designed. The HRM method was used to analyze all the samples, and then the results of HRM were verified with DNA sequencing technology. RESULTS: Among 23 specimens of HS patients, 6 cases of heterozygous mutant gene were detected by HRM technology, including 3 cases of D38A mutation and 3 cases of K56E mutation, which were confirmed by DNA sequencing. CONCLUSION: The HRM technology can correctly detect 2 common mutation sites including D38A and K56E in SLC4A1 gene in an efficient, fast, and reliable way, which not only can be used for clinical diagnosis, but also expected to be a new method for clinical researchers to define gene mutation spectrum in HS patients.

Molecular Genetic Mechanisms of Hereditary Spherocytosis: Current Perspectives.

With the widespread use of genetic diagnostic technologies, many novel mutations have been identified in hereditary spherocytosis (HS)-related genes, including SPTA1, SPTB, ANK1, SLC4A1, and EPB42. However, mutations in HS-related genes are dispersed and nonspecific in the diagnosis of some HS patients, indicating significant heterogeneity in the molecular deficiency of HS. It is necessary to provide the molecular and genetic characteristics of these 5 genes for clinicians to examine HS. Here, we reviewed the recent proposed molecular genetic mechanisms of HS.

Association of circulating branched-chain amino acids with cardiometabolic traits differs between adults and the oldest-old.

Branched-chain amino acids (BCAAs) are promising for their potential anti-aging effects. However, findings in adults suggest that circulating BCAAs are associated with cardiometabolic risk. Moreover, little information is available about how BCAAs influence clustered cardiometabolic traits in the oldest-old (>85 years), which are the fastest-growing segment of the population in developed countries. Here, we applied a targeted metabolomics approach to measure serum BCAAs in Chinese participants (aged 21-110 years) based on a longevity cohort. The differences of quantitative and dichotomous cardiometabolic traits were compared across BCAAs tertiles. A generalized additive model (GAM) was used to explore the dose-response relationship between BCAAs and the risk of metabolic syndrome (MetS). Overall, BCAAs were correlated with most of the examined cardiometabolic traits. The odds ratios for MetS across the increasing BCAA tertiles were 3.22 (1.70 - 6.12) and 5.27 (2.88 - 9.94, referenced to tertile 1) after adjusting for age and gender (Ptrend < 0.001). The association still existed after further controlling for lifestyle factors and inflammation factors. However, the correlations between circulating BCAAs and quantitative traits were weakened in the oldest-old, except for lipids, the levels of which were distinctly different from those in adults. The stratified analysis also suggested that the risky BCAAs-MetS association was more pronounced in adults than in the oldest-old. Moreover, generalized additive model (GAM)-based curve-fitting suggested that only when BCAAs exceeded a threshold (approximately 450 µmol/L) was the BCAAs-MetS association significant. The relationship might be aging-dependent and was more pronounced in adults than in the oldest-old.