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Aim Age and lower folate concentrations are well-known risk factors for cardiovascular disease (CVD), but the potential roles of age and folate deficiency in hyperhomocysteinemia (HHcy), especially in HHcy patients with abnormal methylation levels of key enzyme genes promoter in homocysteinemia (Hcy) pathway, have not been thoroughly evaluated. The purpose of this study was to evaluate the relationship between the promoter methylation levels of six key enzyme genes and age and serum folate level to better understand the pathogenesis of HHcy. Methods In 299 HHcy patients, six key enzyme genes promoter methylation was analyzed by PCR amplification and MethylTarget.sup.TM methods. Results The betaine homocysteine methyltransferase (BHMT), Cystathionine [beta]-synthase (CBS), and Methionine synthasegene (MTR) promoter methylation levels were positively associated with age and a negative correlation was found between CBS promoter methylation level and folate levels. However, these associations were not significant after Bonferroni correction. The stratified analysis showed that the methylation level of CBS gene promoter was positively correlated with age in males, and a positive correlation was also found between BHMT gene promoter methylation level and age in HHcy patients with a history of diabetes or hypertension. Moreover, stratified analysis according to sex revealed that the methylation levels of three CpG regions of BHMT_2, CBS_2, and CBS_3 were positively correlated with age in males after Bonferroni correction. Conclusions Our data suggested that age and folate deficiency may increase the risk of HHcy by mediating methylation of the promoter regions of key enzyme genes in the one-carbon metabolism pathway., Author(s): Xiaowen Huang [sup.1] , Qinglin Zhao [sup.1] , Dankang Li [sup.1] , Bingnan Ren [sup.1] , Limin Yue [sup.1] , Fengxian Shi [sup.1] , Xiliang Wang [sup.1] , Caifang [...]

Alveolar macrophages orchestrate the response to viral infections. Age-related changes in these cells may underlie the differential severity of pneumonia in older patients. We performed an integrated analysis of single-cell RNA-Seq data that revealed homogenous age-related changes in the alveolar macrophage transcriptome in humans and mice. Using genetic lineage tracing with sequential injury, heterochronic adoptive transfer, and parabiosis, we found that the lung microenvironment drove an age-related resistance of alveolar macrophages to proliferation that persisted during influenza A viral infection. Ligand-receptor pair analysis localized these changes to the extracellular matrix, where hyaluronan was increased in aged animals and altered the proliferative response of bone marrow-derived macrophages to granulocyte macrophage colony-stimulating factor (GM-CSF). Our findings suggest that strategies targeting the aging lung microenvironment will be necessary to restore alveolar macrophage function in aging., Introduction Advanced age is the most important risk factor for severe disease or death in patients with viral pneumonia, including coronavirus disease 2019 (COVID-19) (1,2). Alveolar macrophages play central roles [...]

Many individuals possess B cells capable of recognizing epitopes on the spike glycoprotein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this issue of the JCI, Paschold and Simnica et al. interrogated the frequency of SARS-CoV-2-specific B cell receptor rearrangements in healthy subjects based on age and cancer status. The authors found that while SARS-CoV-2-specific antibody signatures can be identified in the repertoires of young, healthy individuals, such sequences are less frequent in elderly subjects or patients with cancer. Overall, this study sheds light on B cell repertoire restrictions that might lead to an unfavorable clinical course of coronavirus disease 2019 infection in at-risk populations., Older age and other risk factors The ongoing coronavirus disease 2019 (COVID-19) pandemic is caused by the novel human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While it appears that [...]

Dysfunction of immune and vascular systems has been implicated in aging and Alzheimer disease; however, their interrelatedness remains poorly understood. The complement pathway is a well-established regulator of innate immunity in the brain. Here, we report robust age-dependent increases in vascular inflammation, peripheral lymphocyte infiltration, and blood-brain barrier (BBB) permeability. These phenotypes were subdued by global inactivation and by endothelial cell-specific ablation of C3ar1. Using an in vitro model of the BBB, we identified intracellular [Ca.sup.2+] as a downstream effector of C3a/C3aR signaling and a functional mediator of vascular endothelial cadherin junction and barrier integrity. Endothelial C3ar1 inactivation also dampened microglia reactivity and improved hippocampal and cortical volumes in the aging brain, demonstrating a crosstalk between brain vasculature dysfunction and immune cell activation and neurodegeneration. Further, prominent C3aR-dependent vascular inflammation was also observed in a tau-transgenic mouse model. Our studies suggest that heightened C3a/C3aR signaling through endothelial cells promotes vascular inflammation and BBB dysfunction and contributes to overall neuroinflammation in aging and neurodegenerative disease., Introduction The natural aging process includes functional and structural changes within the brain (1, 2), and these changes have been shown to play a role in decreased neural stem cell [...]

Idiopathic pulmonary fibrosis (IPF) is a chronic age-related lung disease with high mortality that is characterized by abnormal scarring of the lung parenchyma. There has been a recent attempt to define the age-associated changes predisposing individuals to develop IPF. Age-related perturbations that are increasingly found in epithelial cells and fibroblasts from IPF lungs compared with age-matched cells from normal lungs include defective autophagy, telomere attrition, altered proteostasis, and cell senescence. These divergent processes seem to converge in mitochondrial dysfunction and metabolic distress, which potentiate maladaptation to stress and susceptibility to age-related diseases such as IPF. Therapeutic approaches that target aging processes may be beneficial for halting the progression of disease and improving quality of life in IPF patients., Linking aging and chronic lung diseases One of the most remarkable medical accomplishments in the last century has been the increasing longevity of the human population. A decrease in birth [...]

Moraxella catarrhalis is generally associated with upper respiratory tract infections in children and lower respiratory tract infections in adults. However, little is known regarding the population biology of isolates infecting these two age groups. To address this, a population-screening strategy was employed to investigate 195 worldwide M. catarrhalis isolates cultured from children (20 years of age) presenting with respiratory disease in the years 2001-2002. Parameters compared included: genotype analysis; autoagglutination/biofilmforming ability; serum resistance; uspA 1, uspA2, uspA2H, hag and mcaP incidence; copB/LOS/ ompCD/16S rRNA types; and UspA1/Hag expression. A significant difference in biofilm formation (P-0.002), but not in autoagglutination or serum resistance, was observed, as well as significant differences in the incidence of uspA2- and uspA2H-positive isolates, and the distribution of lipooligosaccharide (LOS) types (P

Tests for age-at-onset anticipation based on affected parent-child pairs may not be meaningful. The type I error rate of the test is probably high compared to the statistical power of the test. The type I error rate is elevated because the sample of affected pairs is usually drawn from pedigrees already selected on the basis of the number of affected individuals. Furthermore, the underlying biological model indicates that the power of the test is likely to be quite low for expanding trinucleotide-repeat diseases.

Genetic research shows that the newly-identified gene klotho is responsible for controlling the ageing process in mice. Experiments using transgenic founder mice demonstrate that the absence of klotho, a membrane protein, causes reduced longevity, arteriosclerosis, osteoporosis and other conditions normally associated with the ageing process in human beings. Evidence suggests that klotho may have a signalling function which promotes growth.

The relationship between the incidence the high incidenceof cancer among the elderly and process of aging was explored. Recent animal studies had only confounded reseachers as more of senescence related processes are continuously being uncovered. The role of the immune system had been found to be irrelevant, however, aging rate and the pathophysiology of cancer were found to have a genetic basis.