0000000001323863
AUTHOR
Luca Cavallone
Genetic Background of Centenarians May Be Protective Against Cardiovascular Diseases.
Association between the interleukin-1beta polymorphisms and Alzheimer's disease: a systematic review and meta-analysis.
Abstract The pro-inflammatory cytokine interleukin(IL)-1β is a main component in inflammatory pathways and is overexpressed in the brain of Alzheimer's disease (AD) patients. Several studies report associations between IL-1β polymorphisms and AD, but findings from different studies are controversial. Our aim was to verify the correlation between the single nucleotide polymorphisms (SNPs) of the IL-1β, at sites − 511 and + 3953, and AD by meta-analysis. Computerized bibliographic searches of PUBMED and AlzGene database ( http://www.alzgene.org ) were supplemented with manual searches of reference lists. There is evidence for association between IL-1β + 3953 SNP and AD, with an OR = 1.60 (95%…
Gender-specific association between -1082 IL-10 promoter polymorphism and longevity.
Ageing is characterized by a pro-inflammatory status, which could contribute to the onset of major age-related diseases. Thus, genetic variations in pro- or anti-inflammatory cytokines might influence successful ageing and longevity. IL-10 is an appropriate candidate because it exerts powerful inhibitory effects on pro-inflammatory function. IL-10 production is controlled by several polymorphic elements in the 5' flanking region of IL-10 gene on 1q32 locus, involving alleles at two microsatellite regions and several polymorphisms in promoter region. We analysed in 190 Italian centenarians (99 years old, 159 women and 31 men) and in 26060 years old control subjects (99 women and 161 men), ma…
Inflammation, genetics, and longevity: further studies on the protective effects in men of IL-10 -1082 promoter SNP and its interaction with TNF-alpha -308 promoter SNP.
Ageing is associated with chronic, low grade inflammatory activity leading to long term tissue damage, and systemic chronic inflammation has been found to be related to mortality risk from all causes in older persons.1 Also, the genetic constitution of the organism interacting with systemic inflammation may cause defined organ specific illnesses. Thus, age related diseases such as Alzheimer’s disease (AD), Parkinson’s disease, atherosclerosis, type 2 diabetes, sarcopenia, and osteoporosis, are initiated or worsened by systemic inflammation, suggesting the critical importance of unregulated systemic inflammation in the shortening of survival in humans.1–3 Accordingly, proinflammatory cytokin…
Genes involved in immune response/inflammation, IGF1/insulin pathway and response to oxidative stress play a major role in the genetics of human longevity: the lesson of centenarians
In this paper, we review data of recent literature on the distribution in centenarians of candidate germ-line polymorphisms that likely affect the individual chance to reach the extreme limit of human life. On the basis of previous observations on the immunology, endocrinology and cellular biology of centenarians we focused on genes that regulate immune responses and inflammation (IL-6, IL-1 cluster, IL-10), genes involved in the insulin/IGF-I signalling pathway and genes that counteract oxidative stress (PON1). On the whole, data indicate that polymorphisms of these genes likely contribute to human longevity, in accord with observations emerging from a variety of animal models, and suggest…
Opposite role of CCR5 polymorphisms in cardiovascular diseases and longevity.
PROTECTIVE DETERMINANTS AGAINST CARDIOVASCULAR DISEASES ARE PRESENT IN GENETIC BACKGROUND OF CENTENARIANS.
Longevity in: Cytokine Gene Polymorphisms in multifactorial conditions. (K. Vandenbroeck ed.)
Association between platelet endothelial cellular adhesion molecule 1 (PECAM-1/CD31) polymorphisms and acute myocardial infarction: a study in patients from Sicily
Summary Adhesion of circulating cells to the arterial surface is among the first detectable events in atherogenesis. Cellular adhesion molecules, expressed by the vascular endothelium and by circulating leucocytes, mediate cell recruitment and their transendothelial migration. Platelet endothelial cellular adhesion molecule 1 (PECAM-1/CD31), involved in this migration, has been associated with the developmental course of atherosclerosis. A few studies have investigated an association between coronary heart disease and single nucleotide polymorphisms (SNPs) located in functionally important domains of the PECAM-1/CD31 gene. In particular, Ser563Asn and Gly670Arg SNPs have been described as s…
Ageing, longevity, inflammation and cancer
The role of IL-1 gene cluster in longevity: a study in Italian population.
In this study, we analysed the polymorphic variants of IL-1alpha (C-T transition at position -889), IL-1beta (C-T transition at position -511) and IL-1 receptor antagonist (Ra) (86-bp repeated sequence in intron 2) in 1131 subjects (453 females and 678 males) from Northern and Central Italy, including 134 centenarians, to evaluate whether IL-1 cluster alleles might be differently represented in people selected for longevity. In addition, IL-1Ra and IL-1beta plasma levels were quantified by ELISA in 130 randomly selected subjects. No significant differences in the genotype and allele frequency distributions were observed between young, elderly and centenarian subjects. IL-1Ra plasma levels s…
Aging, longevity, inflammation, and cancer.
Cancer rates increase sharply with age in both sexes, and the majority of cases of cancer occur in patients over the age of 65 years. However, the incidence and mortality for cancer level off around 85-90 years of age, followed by a plateau, or even a decline in the last decades of life. Therefore, it seems reasonable to conclude that centenarians are endowed with a peculiar resistance to cancer. Tumor progression is a complex process that depends on interactions between tumor and host cells. One aspect of the host response, the inflammatory response, is of particular interest because it includes the release of proinflammatory cytokines, some of which may promote tumor growth and hence infl…
Opposite effects of interleukin 10 common gene polymorphisms in cardiovascular diseases and in successful ageing: genetic background of male centenarians is protective against coronary heart disease
Many aspects of ageing involve inflammatory processes. We evaluated the association with longevity of alleles of IL10 and TNFa, known to have opposite functions in inflammatory reactions, IL-10 acting predominantly as an anti-inflammatory and TNF-a as a proinflammatory factor. The number of male centenarians homozygous for the –1082G genotype, suggested to be associated with high IL-10 production, was significantly increased in comparison with younger control subjects. No significant differences were observed between women and controls. The genotypic frequencies of the TNFa promoter SNPs 308G and 308A, suggested to be associated with low and high TNF-a production respectively, were not sign…