Intrinsic aerobic capacity sets a divide for aging and longevity

<p><b>Rationale:</b> Low aerobic exercise capacity is a powerful predictor of premature morbidity and mortality for healthy adults as well as those with cardiovascular disease. For aged populations, poor performance on treadmill or extended walking tests indicates closer proximity to future health declines. Together, these findings suggest a fundamental connection between aerobic capacity and longevity.</p> <p><b>Objectives:</b> Through artificial selective breeding, we developed an animal model system to prospectively test the association between aerobic exercise capacity and survivability (aerobic hypothesis).</p> <p><b>Methods and Results:</b> Laboratory rats of widely diverse genetic backgrounds (N:NIH stock) were selectively bred for low or high intrinsic (inborn) treadmill running capacity. Cohorts of male and female rats from generations 14, 15, and 17 of selection were followed for survivability and assessed for age-related declines in cardiovascular fitness including maximal oxygen uptake (VO<sub>2max</sub>), myocardial function, endurance performance, and change in body mass. Median lifespan for low exercise capacity rats was 28% to 45% shorter than high capacity rats (hazard ratio, 0.06; P<0.001). VO<sub>2max</sub>, measured across adulthood was a reliable predictor of lifespan (P<0.001). During progression from adult to old age, left ventricular myocardial and cardiomyocyte morphology, contractility, and intracellular Ca<sup>2+</sup> handling in both systole and diastole, as well as mean blood pressure, were more compromised in rats bred for low aerobic capacity. Physical activity levels, energy expenditure (Vo<sub>2</sub>), and lean body mass were all better sustained with age in rats bred for high aerobic capacity.</p> <p><b>Conclusions:</b> These data obtained from a contrasting heterogeneous model system provide strong evidence that genetic segregation for aerobic exercise capacity can be linked with longevity and are useful for deeper mechanistic exploration of aging.</p&gt

Scalable production of large quantities of defect-free few-layer graphene by shear exfoliation in liquids

To progress from the laboratory to commercial applications, it will be necessary to develop industrially scalable methods to produce large quantities of defect-free graphene. Here we show that high-shear mixing of graphite in suitable stabilizing liquids results in large-scale exfoliation to give dispersions of graphene nanosheets. X-ray photoelectron spectroscopy and Raman spectroscopy show the exfoliated flakes to be unoxidized and free of basal-plane defects. We have developed a simple model that shows exfoliation to occur once the local shear rate exceeds 10(4) s(-1). By fully characterizing the scaling behaviour of the graphene production rate, we show that exfoliation can be achieved in liquid volumes from hundreds of millilitres up to hundreds of litres and beyond. The graphene produced by this method performs well in applications from composites to conductive coatings. This method can be applied to exfoliate BN, MoS2 and a range of other layered crystals

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Influenza immunization among Chinese seniors: Urgent calling for improving vaccination coverage, education, and research

It is with great pleasure that we provide this commentary with a focus on influenza vaccination for an expert consensus entitled “Recommendations for influenza and Streptococcus pneumoniae vaccination in elderly people in China” to be published in this issue of Aging Medicine.1 Influenza is a major global public health burden with pandemic threat. Seasonal influenza infection is responsible for 3‐5 million severe illness cases and 290 000‐650 000 respiratory deaths annually worldwide.2, 3 According to the Centers for Disease Control and Prevention (CDC), influenza affects 5%‐20% of the population each year in the United States.4 It is estimated that influenza causes 226 000 excess hospitalizations, 25 000‐69 000 deaths, and US $87 billion excess health‐care cost with over 600 000 life‐years lost annually.5, 6 Among all infectious diseases, influenza is foremost in its age‐related increase in serious complications, leading to hospitalization, catastrophic disability, and death in older adults.7, 8 Moreover, influenza frequently causes exacerbation of many chronic conditions that are common in older adults, including cardiovascular diseases,9, 10 further indirectly impacting senior health and mortality. In fact, over 90% of influenza‐related mortality occurs in persons aged over 65 years.11 In the United States, influenza and its secondary pneumonia are the fourth leading cause of death in this population.12 Therefore, prevention and treatment of influenza in older adults have become a major public health priority

Connection between Systemic Inflammation and Neuroinflammation Underlies Neuroprotective Mechanism of Several Phytochemicals in Neurodegenerative Diseases

Oxidative damage, mitochondrial dysfunction, and neuroinflammation are strongly implicated in the pathogenesis of neurodegenerative diseases including Alzheimer’s disease (AD) and Parkinson’s disease (PD), and a substantial portion of elderly population at risk of these diseases requires nutritional intervention to benefit health due to lack of clinically relevant drugs. To this end, anti-inflammatory mechanisms of several phytochemicals such as curcumin, resveratrol, propolis, polyunsaturated fatty acids (PUFAs), and ginsenosides have been extensively studied. However, correlation of the phytochemicals with neuroinflammation or brain nutrition is not fully considered, especially in their therapeutic mechanism for neuronal damage or dysfunction. In this article, we review the advance in antioxidative and anti-inflammatory effects of phytochemicals and discuss the potential communication with brain microenvironment by improved gastrointestinal function, enhanced systemic immunity, and neuroprotective outcomes. These data show that phytochemicals may modulate and suppress neuroinflammation of the brain by several approaches: (1) reducing systemic inflammation and infiltration via the blood-brain barrier (BBB), (2) direct permeation into the brain parenchyma leading to neuroprotection, (3) enhancing integrity of disrupted BBB, and (4) vagal reflex-mediated nutrition and protection by gastrointestinal function signaling to the brain. Therefore, many phytochemicals have multiple potential neuroprotective approaches contributing to therapeutic benefit for pathogenesis of neurodegenerative diseases, and development of strategies for preventing these diseases represents a considerable public health concern and socioeconomic burden