Age and Gender-related Variations of Molecular and Phenotypic Parameters in A Cohort of Sicilian Population: from Young to Centenarians
People are living longer, but lifespan increase does not coincide with a boost in health-span. Thus, improving the quality of life of older people is a priority. Centenarians reach extreme longevity in a relatively good health status, escaping or delaying fatal or strongly invalidating diseases. Therefore, studying processes involved in longevity is important to explain the biological mechanisms of health and well-being, since knowledge born from this approach can provide valuable information on how to slow aging. We performed the present study in a well characterized very homogeneous sample of 173 people from Western Sicily, to update existing literature on some phenotypic aspects of aging…
Genetically predicted longer telomere length is associated with increased risk of B-cell lymphoma subtypes
International audience; Evidence from a small number of studies suggests that longer telomere length measured in peripheral leukocytes is associated with an increased risk of non-Hodgkin lymphoma (NHL). However, these studies may be biased by reverse causation, confounded by unmeasured environmental exposures and might miss time points for which prospective telomere measurement would best reveal a relationship between telomere length and NHL risk. We performed an analysis of genetically inferred telomere length and NHL risk in a study of 10 102 NHL cases of the four most common B-cell histologic types and 9562 controls using a genetic risk score (GRS) comprising nine telomere length-associa…
The Phenotypic Characterization of the Cammalleri Sisters, an Example of Exceptional Longevity
This article shows demographic, clinical, anamnestic, cognitive, and functional data as well as biochemical, genetic, and epigenetic parameters of two exceptional siblings: Diega (supercentenarian) and Filippa (semisupercentenarian) Cammalleri. The purpose of this study is to provide new insights into the extreme phenotypes represented by semisupercentenarians and supercentenarians. Different studies have been published on supercentenarians, but to the best of our knowledge, this is the only concerning two sisters and the most detailed from a phenotypic point of view. Our findings agree with the suggestion that supercentenarians have an increasing relative resistance to age-related diseases…
Genome-wide homozygosity and risk of four non-Hodgkin lymphoma subtypes
Aim: Recessive genetic variation is thought to play a role in non-Hodgkin lymphoma (NHL) etiology. Runs of homozygosity (ROH), defined based on long, continuous segments of homozygous SNPs, can be used to estimate both measured and unmeasured recessive genetic variation. We sought to examine genome-wide homozygosity and NHL risk.Methods: We used data from eight genome-wide association studies of four common NHL subtypes: 3061 chronic lymphocytic leukemia (CLL), 3814 diffuse large B-cell lymphoma (DLBCL), 2784 follicular lymphoma (FL), and 808 marginal zone lymphoma (MZL) cases, as well as 9374 controls. We examined the effect of homozygous variation on risk by: (1) estimating the fraction o…
Pro-inflammatory status is not a limit for longevity: case report of a Sicilian centenarian
Most studies on centenarians represent them as the best model of ageing. They are defined “delayers”, if they exhibit age-related diseases between 80 and 99 years, “survivors” if they show clinically demonstrable diseases before the age of 80 years, and “escapers” when they attain their 100th year of life without any common age-associated pathologies.
miR-126-3p and miR-21-5p as Hallmarks of Bio-Positive Ageing; Correlation Analysis and Machine Learning Prediction in Young to Ultra-Centenarian Sicilian Population
Human ageing can be characterized by a profile of circulating microRNAs (miRNAs), which are potentially predictors of biological age. They can be used as a biomarker of risk for age-related inflammatory outcomes, and senescent endothelial cells (ECs) have emerged as a possible source of circulating miRNAs. In this paper, a panel of four circulating miRNAs including miR-146a-5p, miR-126-3p, miR-21-5p, and miR-181a-5p, involved in several pathways related to inflammation, and ECs senescence that seem to be characteristic of the healthy ageing phenotype. The circulating levels of these miRNAs were determined in 78 healthy subjects aged between 22 to 111 years. Contextually, extracellular miR-1…
Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes.
International audience; Epidemiologic studies show an increased risk of non-Hodgkin lymphoma (NHL) in patients with autoimmune disease (AD), due to a combination of shared environmental factors and/or genetic factors, or a causative cascade: chronic inflammation/antigen-stimulation in one disease leads to another. Here we assess shared genetic risk in genome-wide-association-studies (GWAS). Secondary analysis of GWAS of NHL subtypes (chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, and marginal zone lymphoma) and ADs (rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis). Shared genetic risk was assessed by (a) description of regional g…
Possible Association of Telomere Length with Sleep Duration. A Preliminary Pilot study in a Sicilian Cohort with Centenarians
Telomere length (TL) is considered a biomarker of ageing although this topic is still debated. Also, sleep pattern changes are physiological part of the normal ageing process. In fact, it is widely recognized that sleep duration declines with age, leading to dysregulation of circadian rhythms. The aim of our study was to analyse the possible association of sleep duration with TL in a sample of 135 subjects with ages ranging from 20 to 111 years, recruited from Palermo and neighbouring municipalities in Sicily (Italy). Preliminary data suggest that relative TL (RTL) decreases with age in both men and women. However, at older ages, the difference between men and women tends to narrow. Nonagen…
Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for Thirteen Cancer Types
BACKGROUND: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites.METHODS: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cance…