Age and Age-Related Diseases: Role of Inflammation Triggers and Cytokines.

Cytokine dysregulation is believed to play a key role in the remodeling of the immune system at older age, with evidence pointing to an inability to fine-control systemic inflammation, which seems to be a marker of unsuccessful aging. This reshaping of cytokine expression pattern, with a progressive tendency toward a pro-inflammatory phenotype has been called "inflamm-aging." Despite research there is no clear understanding about the causes of "inflamm-aging" that underpin most major age-related diseases, including atherosclerosis, diabetes, Alzheimer's disease, rheumatoid arthritis, cancer, and aging itself.

Genes and life-style factors in BELFAST nonagenarians: Nature, Nurture and Narrative.

Understanding how to 'Age Longer and Age Well' is a priority for people personally, for populations globally and for government policy. Nonagenarians are the oldest members of our societies and survivors of their generation. Approximately 10 % of nonagenarians reach 90 years and beyond in good condition and seem to have a combination of both age-span and health-span.

Deletions in 14q24.1q24.3 are associated with congenital heart defects, brachydactyly, and mild intellectual disability.

Interstitial deletions of chromosome band 14q24.1q24.3 are apparently very rare.

Killer Immunoglobulin-like Receptors (KIR) haplogroups A and B track with Natural Killer Cells and Cytokine Profile in Aged Subjects: Observations from Octo/Nonagenarians in the Belfast Elderly Longitudinal Free-living Aging STudy (BELFAST).

Background: Natural Killer Cells (NK) play an important role in detection and elimination of virus-infected, damaged or cancer cells. NK cell function is guided by expression of Killer Immunoglobulin-like Receptors (KIRs) and contributed to by the cytokine milieu. KIR molecules are grouped on NK cells into stimulatory and inhibitory KIR haplotypes A and B, through which NKs sense and tolerate HLA self-antigens or up-regulate the NK-cytotoxic response to cells with altered HLA self-antigens, damaged by viruses or tumours.

Mitochondrial J haplogroup is associated with lower blood pressure and anti-oxidant status: findings in octo/nonagenarians from the BELFAST Study.

Mitochondria produce cellular energy but also free-radicals, which damage cells despite an array of endogenous anti-oxidants. In Northern Europe, the mitochondrial haplogroup J has been related to longevity in nonagenarians and centenarians but also with age-related disease. Hypertension is an important contributor to atherosclerotic-related diseases and its pathogenesis is associated with increased oxidative stress.

Blood pressure and TNF-α act synergistically to increase leucocyte CD11b adhesion molecule expression in the BELFAST study: implications for better blood pressure control in ageing.

Hypertension, a key risk factor for stroke, cardiovascular disease and dementia, is associated with chronic vascular inflammation, and although poorly understood, putative mechanisms include pro-inflammatory responses induced by mechanical stretching, with cytokine release and associated up-regulated expression of adhesion molecules. Because blood pressure increases with age, we measured baseline and tumour necrosis alpha (TNF-α)-stimulated CD11b/CD18 adhesion molecule expression on leucocytes to assess any association between the two. In 38 subjects (mean age 85 years), consecutively enrolled from Belfast Elderly Longitudinal Free-Living Aging Study (BELFAST), baseline and TNF-α-stimulated CD11b/CD18 expression on separated monocytes and neutrophils increased with systolic blood pressure >120 mmHg (p = 0.

Delineation of a recognisable phenotype of interstitial deletion 3 (q22.3q25.1) in a case with previously unreported truncus arteriosus.

Interstitial deletions of chromosome 3q22.3-25.1 are very rare with only five previous reports of deletions in this region [1,2,4,7,9].

Seasonal changes in platelets, fibrinogen and factor VII in elderly people.

Background: an increase in mean platelet volume and a decrease in platelet total have been reported following stroke and increased mean platelet volume in acute myocardial infarction has been shown to be predictive of mortality.

Objective: given the established seasonal variation in morbidity and mortality from cardiovascular disease and various risk factors for the disease, we explored the seasonal variation in mean platelet volume and platelet total.

Methods: we assessed levels of platelet count, platelet volume, fibrinogen, factor VII, core body and ambient temperatures in 54 healthy community dwelling elderly volunteers over a period of 1 year.

Interleukin-6-gene C/G 174 polymorphism in nonagenarian and octogenarian subjects in the BELFAST study. Reciprocal effects on IL-6, soluble IL-6 receptor and for IL-10 in serum and monocyte supernatants.

In this study, we have assessed any change in the frequency of the GG homozygotes of the 174 IL-6 polymorphism with increasing age, arguing that if IL-6 tracks with functional disability and age-related diseases, then there may be attrition or reduction in the frequency of homozgyous subjects, who produce higher levels of IL-6 in serum, in older survivors in a population. We have tested this hypothesis in a large group of free-living, mentally competent, nonagenarian and octogenarian subjects from the Belfast Elderly Longitudinal Ageing Study-BELFAST study and found that the frequency of GG homozygotes with IL-6-174C/G polymorphism decreases with age by about 10%, compared with young controls. In addition we find that CC homozygotes have higher serum levels of IL-6 levels compared with GG (P=0.

A whole blood method for measurement of intracellular TNF-alpha, IFN-gamma and IL-2 expression in stimulated CD3+ lymphocytes: differences between young and elderly subjects.

Cytokines, the central regulators of leucocyte growth and differentiation, are produced by a wide variety of cell types, target various cell subsets and exhibit numerous biological activities. Cytokine dysregulation is believed to play a role in the remodelling of the immune system in old age, however, previous reports of cytokine levels in elderly subjects have been conflicting, possibly due to methodologies employed. We used the relatively new technique of intracellular cytokine detection by flow cytometry to measure cytokine production in CD3+ lymphocytes from young and elderly subjects, but applied it to whole blood, thereby eliminating the need for laborious cell separation techniques and maintaining cells in their normal physiological environment.

Serum heat shock protein and anti-heat shock protein antibody levels in aging.

We have previously reported the presence of Hsp60 and Hsp70 in the peripheral circulation of normal individuals. Given that the capacity to generate stress proteins declines with age, this study measured Hsp60 and Hsp70 levels in the sera of 60 individuals aged between 20 and 96 years. Levels of anti-human Hsp60, anti-human Hsp70 and anti-mycobacterial Hsp65 antibody were also measured.

Total serum IL-12 and IL-12p40, but not IL-12p70, are increased in the serum of older subjects; relationship to CD3(+)and NK subsets.

Interleukin 12 (IL-12), a central cytokine acting on T and natural killer (NK) cells, directs proliferation of activated T lymphocytes towards a Th1 phenotype. The heterodimeric molecule IL-12p70, equates with IL-12 biological activity, while IL-12p40 may antagonize IL-12 and inhibit cytotoxic T lymphocyte (CTL) generation in vitro. This study characterizes age-related changes in serum total IL-12, IL-12p70 and IL-12p40 relating them with CD3(+), NK and related subsets from subjects, aged 30-96 years.

Particulate air pollution and the blood.

Background: Particulate air pollution has been associated with excess deaths from, and increases in hospital admissions for, cardiovascular disease among older people. A study was undertaken to determine whether this may be a consequence of alterations in the blood, secondary to pulmonary inflammation caused by the action of fine particles on alveolar cells, by repeatedly measuring haematological factors in older people and relating them to measurements of exposure to airborne particles.

Methods: One hundred and twelve individuals aged 60+ years in two UK cities provided repeated blood samples over 18 months, 108 providing the maximum of 12 samples.

Age-related reference intervals for lymphocyte subsets in whole blood of healthy individuals.

Enumeration of various lymphocyte subsets is used widely in the diagnosis and monitoring of various disease states. With the development of flow cytometric technology and whole blood analysis, methodologies have become more sensitive. It is therefore important to establish reference intervals in normal, healthy individuals using these techniques to give a better indication of the border between health and disease.

CD69, CD25, and HLA-DR activation antigen expression on CD3+ lymphocytes and relationship to serum TNF-alpha, IFN-gamma, and sIL-2R levels in aging.

Aging is associated with changes in lymphocyte subsets and unexplained HLA-DR upregulation on T-lymphocytes. We further investigated this activation, by measuring early (CD69), middle (CD25), and late (HLA-DR) T-lymphocyte activation markers on CD3+ lymphocytes, across subjects (20-100 years) together with serum tumor necrosis factor (TNF-alpha), interferon-gamma (IFN-gamma), and soluble interleukin-2 receptor (sIL-2R). HLA-DR was present as a CD3+ HLA-DR+ subset that constituted 8% of total lymphocytes, increased twofold with age and included CD4+, CD8+, and CD45RA+ phenotypes.

Measurement of fibrinogen in frozen plasma.

Several large studies have compared fibrinogen measurements determined over a particular time interval. These assays are subject to difficulties encountered by all laboratories on tests carried out over a period of time such as assay drift. To avoid this problem, plasma can be stored frozen and fibrinogen determined in a large number of samples simultaneously.

Changes in natural killer cells, the CD57CD8 subset, and related cytokines in healthy aging.

Aging has been shown to be accompanied by various changes in the lymphocyte subset distribution in the elderly. We have investigated more fully, and in a large number of subjects, age-related changes within several subpopulations bearing natural killer (NK) cell-associated surface antigens and changes in several cytokines involved in NK cell expansion. A total of 229 healthy subjects from all decades of life from 20 to 98 years of age was included in this cross-sectional study.