A novel B cell population revealed by a CD38/CD24 gating strategy: CD38−CD24− B cells in centenarian offspring and elderly people

The B cell arm of adaptive immunity undergoes significant modifications with age. Elderly people are characterized by impaired B cell responses reflected in a reduced ability to effectively respond against viruses and bacteria. Alterations of immunity with advancing age (immunosenescence) have been widely studied in centenarians who are considered a good example of successful aging. In recent years, attention has shifted to centenarian offspring (CO) as a model of people genetically advantaged for healthy aging and longevity. Here, we describe the preliminary characterization of a proposed new population of memory B cells, defined as CD19(+)CD38(-)CD24(-), which we find at higher frequencie…

Centenarian offspring: A model for understanding longevity

Abstract: A main objective of current medical research is to improve the life quality of elderly people as priority of the continuous increase of ageing population. This phenomenon implies several medical, economic and social problems because of dramatic increase in number of non autonomous individuals affected by various pathologies. Accordingly, the research interest is focused on understanding the biological mechanisms involved in determining the positive ageing phenotype, i.e. the centenarian phenotype. In achieving this goal the choice of an appropriate study models is fundamental. Centenarians have been used as an optimal model for successful ageing. However, this model shows several …

Double Negative (IgG+IgD-CD27-) B Cells are Increased in a Cohort of Moderate-Severe Alzheimer’s Disease Patients and Show a Pro-Inflammatory Trafficking Receptor Phenotype

Alzheimer's disease (AD) is a progressive, irreversible, and debilitating disease for which no effective preventive or disease modifying therapies or treatments have so far been detected. The crucial step in AD pathogenesis is the production of amyloid-42 peptide, which causes chronic inflammation. Activated cells in the central nervous system (CNS) produce pro- inflammatory mediators that lead to the recruitment of myeloid or lymphocytic cells. As a consequence, the communication between the CNS and peripheral blood of AD subjects could influence the lymphocyte distribution and/or the expression of phenotypic markers. In the present paper, we show a significant decrease in total CD19 + B l…

Are the leukocyte telomere length attrition and telomerase activity alteration potential predictor biomarkers for sporadic TAA in aged individuals?

A large variability in occurrence, complications, and age/gender manifestations characterizes individual susceptibility of sporadic thoracic aortic aneurysms (TAA), even in subjects with the same risk factor profiles. The reasons are poorly understood. On the other hand, TAA pathophysiology mechanisms remain unclear than those involved in abdominal aorta aneurysms. However, recent evidence is suggesting a crucial role of biological ageing in inter-individual risk variation of cardiovascular diseases, including sporadic TAA. Biological age rather than chronological age is a better predictor of vascular risk. Relevant assumptions support this concept. In confirming this evidence and our preli…

Vascular Aging effect on Medial aorta degeneration: focus on blood keukocyte telomere lenght in Hypertensive and old patients with sporadic thoracic aortic aneurysm

TRafficking profile in naive and memory B cells in young and old subjects

Evidence for Less Marked Potential Signs of T-Cell Immunosenescence in Centenarian Offspring Than in the General Age-Matched Population

People may reach the upper limits of the human life span at least partly because they have maintained more appropriate immune function, avoiding changes to immunity termed "immunosenescence." Exceptionally long-lived people may be enriched for genes that contribute to their longevity, some of which may bear on immune function. Centenarian offspring would be expected to inherit some of these, which might be reflected in their resistance to immunosenescence, and contribute to their potential longevity. We have tested this hypothesis by comparing centenarian offspring with age-matched controls. We report differences in the numbers and proportions of both CD4(+) and CD8(+) early- and late-diffe…

Efficacy of Rapamycin as Inducer of Hb F in Primary Erythroid Cultures from Sickle Cell Disease and β-Thalassemia Patients.

Phenotypic improvement of hemoglobinopathies such as sickle cell disease and β-thalassemia (β-thal) has been shown in patients with high levels of Hb F. Among the drugs proposed to increase Hb F production, hydroxyurea (HU) is currently the only one proven to improve the clinical course of these diseases. However, Hb F increase and patient's response are highly variable, indicating that new pharmacological agents could be useful for patients not responding to HU or showing a reduction of response during long-term therapy. In this study we evaluated the efficacy of rapamycin, a lypophilic macrolide used for the prevention of acute rejection in renal transplant recipients, as an inducer of Hb…

Immunosenescence, inflammation and Alzheimer’s disease

Abstract Ageing impacts negatively on the development of the immune system and its ability to fight pathogens. Progressive changes in the T-cell and B-cell systems over the lifespan of individuals have a major impact on the capacity to respond to immune challenges. The cumulative age-associated changes in immune competence are termed immunosenescence that is characterized by changes where adaptive immunity deteriorates, while innate immunity is largely conserved or even upregulated with age. On the other hand, ageing is also characterized by “inflamm-ageing”, a term coined to explain the inflammation commonly present in many age-associated diseases. It is believed that immune inflammatory p…

B CELL CHANGES IN AGING

The aging of the immune system is a gradual and dynamic process that modifies some immunological functions. These changes are known as “immunosenescence” that have a great impact on immune performance in late life, contributing to the decreased ability of the elderly people to respond to emerging pathogens and to the decreased responsiveness to vaccinations. It is known that the adaptive immune functions are affected in the aged. In particular, with aging, the acquired compartment of the immune system shows significant modifications in both T and B cell branches. Thus, the adaptive immune response of elderly people is qualitatively and quantitatively reduced when compared to that observed i…

Double Negative (CD19+IgG+IgD-CD27-) B Lymphocytes: A New Insight from Telomerase in Healthy Elderly, in Centenarian Offspring, and in Alzheimer’s Disease Patients

Background: We have previously reported the increase of IgD-CD27- (Double Negative, DN) B cell population in the aged. These memory B cells have short telomeres and poor abilities to proliferate in vitro. Here, we investigated whether the low ability of DN B cells to proliferate depends on the expression levels of the CD307d and CD22 inhibitory receptors or whether DN B cells can proliferate and reactivate telomerase by the engagement of both innate and adaptive immune receptors. Methods: Phenotypic analyses were made by using flow cytometry. Quantitative analysis of telomerase activity was made by using a TRAP and a photometric enzyme immunoassay in young, healthy elderly, centenarian offs…

Expression of calpain-calpastatin system (CCS) member proteins in human lymphocytes of young and elderly individuals; pilot baseline data for the CALPACENT project

Abstract Background Ubiquitous system of regulatory, calcium-dependent, cytoplasmic proteases – calpains – and their endogenous inhibitor – calpastatin – is implicated in the proteolytic regulation of activation, proliferation, and apoptosis of many cell types. However, it has not been thoroughly studied in resting and activated human lymphocytes yet, especially in relation to the subjects’ ageing process. The CALPACENT project is an international (Polish-Italian) project aiming at verifying the hypothesis of the role of calpains in the function of peripheral blood immune cells of Polish (Pomeranian) and Italian (Sicilian) centenarians, apparently relatively preserved in comparison to the g…

Molecular Analysis of the Official Algerian Olive Collection Highlighted a Hotspot of Biodiversity in the Central Mediterranean Basin

Genetic diversity and population structure studies of local olive germplasm are important to safeguard biodiversity, for genetic resources management and to improve the knowledge on the distribution and evolution patterns of this species. In the present study Algerian olive germplasm was characterized using 16 nuclear (nuSSR) and six chloroplast (cpSSR) microsatellites. Algerian varieties, collected from the National Olive Germplasm Repository (ITAFV), 10 of which had never been genotyped before, were analyzed. Our results highlighted the presence of an exclusive genetic core represented by 13 cultivars located in a mountainous area in the North-East of Algeria, named Little Kabylie. Compar…

Genetics of longevity. Data from the studies on Sicilian centenarians

Abstract The demographic and social changes of the past decades have determined improvements in public health and longevity. So, the number of centenarians is increasing as a worldwide phenomenon. Scientists have focused their attention on centenarians as optimal model to address the biological mechanisms of "successful and unsuccessful ageing". They are equipped to reach the extreme limits of human life span and, most importantly, to show relatively good health, being able to perform their routine daily life and to escape fatal age-related diseases, such as cardiovascular diseases and cancer. Thus, particular attention has been centered on their genetic background and immune system. In thi…

Transcriptome analysis and codominant markers development in caper, a drought tolerant orphan crop with medicinal value.

AbstractCaper (Capparis spinosa L.) is a xerophytic shrub cultivated for its flower buds and fruits, used as food and for their medicinal properties. Breeding programs and even proper taxonomic classification of the genus Capparis has been hampered so far by the lack of reliable genetic information and molecular markers. Here, we present the first genomic resource for C. spinosa, generated by transcriptomic approach and de novo assembly. The sequencing effort produced nearly 80 million clean reads assembled into 124,723 unitranscripts. Careful annotation and comparison with public databases revealed homologs to genes with a key role in important metabolic pathways linked to abiotic stress t…

Trafficking phenotype and production of granzyme B by double negative B cells (IgG(+)IgD(-)CD27(-)) in the elderly.

The impairment of humoral immune response in elderly humans has been extensively demonstrated. We have reported the increase of memory B cells (IgG(+)IgD(-)CD27(-), double negative, DN) population in the elderly, in which there is also a typical inflammatory micro-environment. In order to evaluate whether this pro-inflammatory status could influence the trafficking phenotype of naïve/memory B cells, we have assessed the expression of CCR7, CCR6, CXCR3, CXCR4, CXCR5 and CD62L on naïve/memory B cell subpopulations in young and elderly subjects. Moreover, the combination of pro-inflammatory interleukin-21 (IL-21) and B cell receptor (BCR) stimulation enables B cells to produce and secrete gran…