265 research outputs found
Inflammation, genetic background and longevity
Ageing is an inexorable intrinsic process
that affects all cells, tissues, organs and individuals.
Due to a diminished homeostasis and increased
organism frailty, ageing causes a reduction of the
response to environmental stimuli and, in general, is
associated to an increased predisposition to illness and
death. Actually, it is characterized by a state of reduced
ability to maintain health and general homeodynamics
of the organism.Alarge part of the ageing phenotype is
explained by an imbalance between inflammatory and
anti-inflammatory networks, which results in the low
grade chronic pro-inflammatory status of ageing,
‘‘inflamm-ageing’’. It is strictly linked to immunosenescence,
and on the whole they are the major
contributory factors to the increased frequency of
morbidity and mortality among elderly. Inflammageing
is compatible with longevity; even if centenarians
have an increased level of inflammatory mediators
in comparison to old subjects and they are very frail,
they also have high level of anti-inflammatory cytokines
together with protective genotypes. Actually,
data on case control studies performed in Italian
centenarians suggest that a pro-inflammatory genotype
is unfavourable to reach extreme longevity in good
health and likely favours the onset of age-related
diseases such as cardiovascular diseases and Alzheimer’s
disease, the leading causes of mortality and
disability in the elderly. However, many associations
between gene variants and longevity have been found
only in Italian population. This should not be unexpected,
since ageing and longevity are complex traits
resulting not only and not exclusively from genetics,
but rather from the interactions between genetics,
environment and chance
The role of immune response in ageing and longevity. A focus on B cell compartment
The improvement of the quality of life of elderly people is going to
become a priority because of the continuous increase in the number
of centenarians. This render the studies of the processes involved in
ageing of critical importance. Centenarians are a widely accepted
model of successful ageing, a complex process which is influenced by
several biological, environmental and lifestyle factors, because they
have reached the extreme limits of life span overcoming the major
age-related diseases. In centenarians model, several aspects have been
studied, as inflammation, immune system, genetics and metabolism,
to understand the secret of their long survival. It has been proposed
that centenarians are characterized by more efficient protective molecules
and biochemical pathways, and show well preserved immune
functions
The Role of Adipose Tissue and Adipokines in Obesity-Related Inflammatory Diseases
Obesity is an energy-rich condition associated with overnutrition, which impairs systemic metabolic homeostasis and elicits stress. It also activates an inflammatory process in metabolically active sites, such as white adipose tissue, liver, and immune cells. As consequence, increased circulating levels of proinflammatory cytokines, hormone-like molecules, and other inflammatory markers are induced. This determines a chronic active inflammatory condition, associated with the development of the obesity-related inflammatory diseases. This paper describes the role of adipose tissue and the biological effects of many adipokines in these diseases
NF-κB pathway activators as potential ageing biomarkers: targets for new therapeutic strategies.
Chronic inflammation is a major biological mechanism underpinning biological ageing process and age-related
diseases. Inflammation is also the key response of host defense against pathogens and tissue injury. Current opinion
sustains that during evolution the host defense and ageing process have become linked together. Thus, the large
array of defense factors and mechanisms linked to the NF-κB system seem to be involved in ageing process. This
concept leads us in proposing inductors of NF-κB signaling pathway as potential ageing biomarkers. On the other
hand, ageing biomarkers, represented by biological indicators and selected through apposite criteria, should help to
characterize biological age and, since age is a major risk factor in many degenerative diseases, could be
subsequently used to identify individuals at high risk of developing age-associated diseases or disabilities. In this
report, some inflammatory biomarkers will be discussed for a better understanding of the concept of biological
ageing, providing ideas on eventual working hypothesis about potential targets for the development of new
therapeutic strategies and improving, as consequence, the quality of life of elderly populatio
Can Alzheimer disease be a form of type 3 diabetes?
Alzheimer disease (AD) and metabolic syndrome are two highly prevalent pathological conditions of Western society due to incorrect diet, lifestyle, and vascular risk factors. Recent data have suggested metabolic syndrome as an independent risk factor for AD and pre-AD syndrome. Furthermore, biological plausibility for this relationship has been framed within the “metabolic cognitive syndrome” concept. Due to the increasing aging of populations, prevalence of AD in Western industrialized countries will rise in the near future. Thus, new knowledge in the area of molecular biology and epigenetics will probably help to make an early molecular diagnosis of dementia. An association between metabolic syndrome and specific single-nucleotide polylmorphisms (SNPs) in the gene INPPL1, encoding for SHIP2, a SH2 domain-containing inositol 5-phosphatase involved in insulin signaling, has been described. According to recent data suggesting that Type 2 diabetes represents an independent risk factor for AD and pre-AD, preliminary results of a case–control study performed to test the putative association between three SNPs in the SHIP2 gene and AD show a trend toward association of these SNPs with AD
La malattia: dagli sciamani alla medicina di precisione
This book is not only an introductory refocusing of the foundations of Pathology
general, but it would also be an excellent guide to intelligently instruct a solid, more advanced
and necessary reform of medical curricula. The General Pathology has represented, at the origins and
in the phase of greater scientific development of medicine, the space for meeting and integration between the two
more advanced experimental applications applied to the study of diseases. A little abandoned in its function
of theoretical synthesis from the advent of EBM (evidence based medicine), in the face of the challenges represented
from the flow of genomic data and from the expectations of seeing a new personalized medicine re-emerge
(because even the Hippocratic one in his methodological aspiration was a cropped medicine
on the individual patient), the General Pathology could return to constitute, and this book is one
valid example, a field of reflection able to re-establish the medicine theoretically, procuring
a scientific reference framework capable of acquiring and transmitting to the doctor the relevant topics
of a humanistic nature
HLA and KIR Frequencies in Sicilian Centenarians
Several studies suggest that human longevity appears to be linked inextricably with optimal functioning of the
immune system, suggesting that specific genetic determinants may reside in loci that regulate the immune response,
as human leukocyte antigen (HLA) and killer cell immunoglobulin-like receptor (KIR) genes. It has been
suggested that longevity is associated with positive selection of alleles (i.e., HLA-DR11) or haplotypes (i.e., HLAB8,
DR3) that confer resistance to infectious disease(s). On the other hand, the cytolytic activity of natural killer
(NK) cells is controlled by activating and inhibitory cell-surface receptors, including KIR. The genetic diversity of
the KIR loci with respect to successful aging has been analyzed only in one study performed in the Irish population.
Although two KIR genes (2DS3, 2DL5) displayed an initial increased frequency in the aged group, the
significance of this association was lost when repeated in a second cohort.We have evaluated by polymerase chain
reaction–sequence-specific primers (PCR-SSP) HLA-DRB1 and KIR receptors=HLA ligands frequencies in centenarians
and controls from Sicily. Our results demonstrate an increase of the HLA DRB1*18 allele in male centenarians
( p¼0.0266, after Bonferroni correction). Concerning KIR, no significant difference was observed after
Bonferroni correction. However, our findings suggest that HLA=KIR=longevity associations are population specific,
being heavily affected by the population-specific genetic and environmental history. This kind of study is
important to better understand aging and longevity, hence enhancing the planning of antiaging strategies
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