Longevity Features Research Articles

1H NMR-Based Metabolomics Reveals the Intrinsic Interaction of Age, Plasma Signature Metabolites, and Nutrient Intake in the Longevity Population in Guangxi, China.

Health and longevity populations have distinct metabolic and nutrient intake profiles. However, the relationship between biomarkers of longevity-related metabolites and dietary nutrient intake profiles, as well as metabolic markers associated with longevity features, have not been fully elucidated. Therefore, 1H nuclear magnetic resonance (1H NMR)-based plasma metabolomics profiling was conducted in the present study to identify potential metabolites which can be used as specific markers for the evaluation of healthy aging. Plasma samples were obtained from centenarians and nonagenarians from the longevous region, and elderly participants aged 60–89 from the longevous region, as well as a low centenarian ratio region. The results showed that participants from longevous regions exhibited higher plasma levels of citrate, tyrosine, choline, carnitine, and valine, as well as lower contents of VLDL, lactate, alanine, N-acetyl glycoprotein (NAG), trimethylamine oxide (TMAO), α-glucose, β-glucose, and unsaturated lipids. The differential plasma metabolites were associated with an alteration in glycolysis/gluconeogenesis; aminoacyl-tRNA biosynthesis; alanine, aspartate, and glutamate metabolism; and phenylalanine, tyrosine, and tryptophan biosynthesis in participants from longevous regions. The signature metabolites were associated with higher dietary fiber intake, as well as lower energy and fat intake. The results of the present study demonstrate key longevity signature metabolites in plasma, and the dietary patterns identified provide a basis for further health and longevity research.

An Empirical Analysis on the Longevity of Dairy Cows in Relation to Economic Herd Performance.

Several studies have stated the various effects of an increased dairy cow longevity on economic herd performance, but empirical studies are lacking. This study aimed to investigate the association between longevity of dairy cows and the economic performance of dairy herds based on longitudinal Dutch accounting data. Herd and farm accounting data (n = 855 herds) over the years 2007–2016 were analyzed. Herd data contained yearly averages on longevity features, herd size and several production variables. Longevity was defined as the age of cows at culling and by lifetime milk production of culled cows. Farm accounting data contained yearly averages on revenues, fixed and variable costs of the herds, by which gross margins were defined. Data was analyzed using generalized linear mixed modeling, with gross margin as dependent variable. The independent variables consisted of average age of culled cows, average lifetime production of culled cows, year, herd size, herd intensity (milk production per ha), herd expansion rate, soil type, milking system, successor availability, total full-time equivalent, heifer ratio (% of heifers per cow) and use of outsourced heifer rearing. Herd was included as a random effect to account for the heterogeneity among herds. Descriptive statistics showed that the average age of culled cows was 5.87 (STD = 0.78) years and the average lifetime milk production of culled cows was 31.87 (STD = 7.56) tons per cow with an average herd size of 89 cows (STD = 38.85). The average age of culled cows was stable over the 10 years (variation between 5.79 AND 5.90 years). The gross margin was on average €24.80/100 kg milk (STD = 4.67), with the lowest value in year 2009 and the highest value in year 2013. Gross margin was not significantly associated with age of culled cows and lifetime milk production of culled cows. Variance in longevity between herds was large (STD = 0.78 years) but herds with a higher longevity did not perform economically better nor worse than herds resulting in lower longevity. This indicates that, within current practice, there is potential for improving longevity in order to meet society's concerns on animal welfare and environmental pollution, without affecting the economic performance of the herd.

Sorafenib promotes graft-versus-leukemia activity in mice and humans through IL-15 production in FLT3-ITD-mutant leukemia cells.

Individuals with acute myeloid leukemia (AML) harboring an internal tandem duplication (ITD) in the gene encoding Fms-related tyrosine kinase 3 (FLT3) who relapse after allogeneic hematopoietic cell transplantation (allo-HCT) have a 1-year survival rate below 20%. We observed that sorafenib, a multitargeted tyrosine kinase inhibitor, increased IL-15 production by FLT3-ITD+ leukemia cells. This synergized with the allogeneic CD8+ T cell response, leading to long-term survival in six mouse models of FLT3-ITD+ AML. Sorafenib-related IL-15 production caused an increase in CD8+CD107a+IFN-γ+ T cells with features of longevity (high levels of Bcl-2 and reduced PD-1 levels), which eradicated leukemia in secondary recipients. Mechanistically, sorafenib reduced expression of the transcription factor ATF4, thereby blocking negative regulation of interferon regulatory factor 7 (IRF7) activation, which enhanced IL-15 transcription. Both IRF7 knockdown and ATF4 overexpression in leukemia cells antagonized sorafenib-induced IL-15 production in vitro. Human FLT3-ITD+ AML cells obtained from sorafenib responders following sorafenib therapy showed increased levels of IL-15, phosphorylated IRF7, and a transcriptionally active IRF7 chromatin state. The mitochondrial spare respiratory capacity and glycolytic capacity of CD8+ T cells increased upon sorafenib treatment in sorafenib responders but not in nonresponders. Our findings indicate that the synergism of T cells and sorafenib is mediated via reduced ATF4 expression, causing activation of the IRF7-IL-15 axis in leukemia cells and thereby leading to metabolic reprogramming of leukemia-reactive T cells in humans. Therefore, sorafenib treatment has the potential to contribute to an immune-mediated cure of FLT3-ITD-mutant AML relapse, an otherwise fatal complication after allo-HCT.

Precision architecture

The processor component of the Hewlett-Packard Precision Architecture system is described. The architecture's goals, how the architecture addresses the spectrum of general-purpose user information processing needs, and some architectural design tradeoffs are examined. Extendibility and longevity features are considered.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>