The surname structure of Trentino (Italy) and its relationship with dialects and genes.

BACKGROUND: Thanks to the availability of rich surname, linguistic and genetic information, together with its geographic and cultural complexity, Trentino (North-Eastern Italy) is an ideal place to test the relationships between genetic and cultural traits. AIM: We provide a comprehensive study of population structures based on surname and dialect variability and evaluate their relationships with genetic diversity in Trentino. SUBJECTS AND METHODS: Surname data were collected for 363 parishes, linguistic data for 57 dialects and genetic data for different sets of molecular markers (Y-chromosome, mtDNA, autosomal) in 10 populations. Analyses relied on different multivariate methods and correlation tests. RESULTS: Besides the expected isolation-by-distance-like patterns (with few local exceptions, likely related to sociocultural instances), we detected a significant and geography-independent association between dialects and surnames. As for molecular markers, only Y-chromosomal STRs seem to be associated with the dialects, although no significant result was obtained. No evidence for correlation between molecular markers and surnames was observed. CONCLUSION: Surnames act as cultural markers as do other words, although in this context they cannot be used as reliable proxies for genetic variability at a local scale.

Gender, aging and longevity in humans: an update of an intriguing/neglected scenario paving the way to a gender-specific medicine.

Data showing a remarkable gender difference in life expectancy and mortality, including survival to extreme age, are reviewed starting from clinical and demographic data and stressing the importance of a comprehensive historical perspective and a gene-environment/lifestyle interaction. Gender difference regarding prevalence and incidence of the most important age-related diseases, such as cardiovascular and neurodegenerative diseases, cancer, Type 2 diabetes, disability, autoimmunity and infections, are reviewed and updated with particular attention to the role of the immune system and immunosenescence. On the whole, gender differences appear to be pervasive and still poorly considered and investigated despite their biomedical relevance. The basic biological mechanisms responsible for gender differences in aging and longevity are quite complex and still poorly understood. The present review focuses on centenarians and their offspring as a model of healthy aging and summarizes available knowledge on three basic biological phenomena, i.e. age-related X chromosome inactivation skewing, gut microbiome changes and maternally inherited mitochondrial DNA genetic variants. In conclusion, an appropriate gender-specific medicine approach is urgently needed and should be systematically pursued in studies on healthy aging, longevity and age-related diseases, in a globalized world characterized by great gender differences which have a high impact on health and diseases.

Centenarians' offspring as a model of healthy aging: a reappraisal of the data on Italian subjects and a comprehensive overview.

Within the scenario of an increasing life expectancy worldwide it is mandatory to identify determinants of healthy aging. Centenarian offspring (CO) is one of the most informative model to identify trajectories of healthy aging and their determinants (genetic and environmental), being representative of elderly in their 70th whose lifestyle can be still modified to attain a better health. This study is the first comprehensive investigation of the health status of 267 CO (mean age: 70.2 years) and adopts the innovative approach of comparing CO with 107 age-matched offspring of non-long-lived parents (hereafter indicated as NCO controls), recruited according to strict inclusion demographic criteria of Italian population. We adopted a multidimensional approach which integrates functional and cognitive assessment together with epidemiological and clinical data, including pro- and anti-inflammatory cytokines and adipokines, lipid profile, and insulin resistance. CO have a lower prevalence of stroke, cerebral thrombosis-hemorrhage, hypertension, hypercholesterolemia, and other minor diseases, lower BMI and waist circumference, a better functional and cognitive status and lower plasma level of FT4 compared to NCO controls. We conclude that a multidimensional approach is a reliable strategy to identify the health status of elderly at an age when interventions to modify their health trajectory are feasible.

Estimating Sampling Selection Bias in Human Genetics: A Phenomenological Approach.

This research is the first empirical attempt to calculate the various components of the hidden bias associated with the sampling strategies routinely-used in human genetics, with special reference to surname-based strategies. We reconstructed surname distributions of 26 Italian communities with different demographic features across the last six centuries (years 1447-2001). The degree of overlapping between "reference founding core" distributions and the distributions obtained from sampling the present day communities by probabilistic and selective methods was quantified under different conditions and models. When taking into account only one individual per surname (low kinship model), the average discrepancy was 59.5%, with a peak of 84% by random sampling. When multiple individuals per surname were considered (high kinship model), the discrepancy decreased by 8-30% at the cost of a larger variance. Criteria aimed at maximizing locally-spread patrilineages and long-term residency appeared to be affected by recent gene flows much more than expected. Selection of the more frequent family names following low kinship criteria proved to be a suitable approach only for historically stable communities. In any other case true random sampling, despite its high variance, did not return more biased estimates than other selective methods. Our results indicate that the sampling of individuals bearing historically documented surnames (founders' method) should be applied, especially when studying the male-specific genome, to prevent an over-stratification of ancient and recent genetic components that heavily biases inferences and statistics.

Arm measurements as determinants of further survival in centenarians.

Being indicators of nutritional and functional status, anthropometric characters may have great prognostic significance for survival at extremely advanced ages. For ethical and practical reasons however it is advisable to use characters such as arm measurements easily measurable even in bedridden subjects. This study compares the influence of some upper arm measurements and of Body Mass Index (BMI) on survival of the 77 subjects aged 98 years and over (98+) recruited within the MALVA project, one of the first Italian population-based studies on extremely old people. Adopting methods for multiple imputation of missing values, Gompertz regression models adjusted for gender and age were estimated for each anthropometric character or combination of characters, i.e. BMI; mid-upper arm circumference (MUAC)+elbow breadth (EB)+triceps skinfold thickness (TSF); corrected arm muscle area (CAMA). Being underweight and having a low CAMA and a low MUAC/high EB were positively associated with an increased risk of death, while no significant association was found with the condition of being overweight/obese and the triceps skinfold thickness. When anthropometric variables were included in regression models along with covariates relating to nutritional and functional status, BMI and MUAC, but not CAMA, emerged as protective factors. It is suggested that MUAC can be recommended in evaluating the health status of extremely old people and that measuring EB may help to estimate the non-boney component of the arm.

Early breakdown of isolation revealed by marriage behaviour in a Ladin-speaking community (Gardena Valley, South Tyrol, Italy, 1825-1924).

The aim of this study was to investigate marriage behaviour from 1825 to 1924 in an Alpine valley inhabited by Ladin speakers (Gardena Valley, South Tyrol, Italy), where the particular geographic, linguistic and economic characteristics may have influenced the level of reproductive isolation. A total of 2183 marriage acts from the two main parishes of Santa Cristina and Ortisei were examined. Birth and residence endogamy, inbreeding coefficients from dispensations and from isonymy, birth place distribution of the spouses and isonymic relationships were analysed in four 25-year sub-periods. All the indicators considered point to a lower level of reproductive isolation at Ortisei, a main centre for the woodcarving industry, which appeared to be experiencing an early and effective breakdown of isolation. Marriage behaviour in the Gardena Valley between 1825 and 1924 seems to have been mostly influenced by socioeconomic factors rather than linguistic and cultural ones.

Migration matrices and surnames in populations with different isolation patterns: Val di Lima (Italian Apennines), Val di Sole (Italian Alps), and La Cabrera (Spain).

Biodemographic methods are widely used to infer the genetic structure of human populations. In this study, we revise and standardize the procedures required by the migration matrix model of Malécot ([1950] Ann Univ Lyon Sci [A] 13:37-60), testing it in large historical-demographic databases of 85 populations from three mountain valleys with different degrees of isolation: Val di Lima (Italian Apennines, 21 parishes), Val di Sole, (Italian Alps, 27 parishes), and La Cabrera (Spain, 37 parishes). An add-on package (Biodem) for the R program is proposed to perform all calculations. Results from migration matrices are compared with those obtained from isonymic relationships. Migration and isonymy matrices are derived from 22,781 marriage records. Matrices are analyzed using a nonlinear isolation-by-distance (IBD) model and multivariate techniques (multidimensional scaling, Procrustes rotation, and cluster analysis). Microdifferentiation levels (F(ST)) from the migration data agree with the observed inbreeding values: higher values are found in La Cabrera (F(ST) = 0.0082), the most isolated population; Val di Lima (F(ST) = 0.0015) and Val di Sole (F(ST) = 0.0012) have lower values due to the larger parish population sizes and greater mobility. Temporal changes of F(ST) and IBD are analyzed using the migration matrix approach. The populations show a marked decline in F(ST) values in time, together with increased population mobility and emigration rates. In all three valleys, marital migration and isonymy yield similar results, suggesting that geographic distance is the most important factor structuring the populations. However, isonymy shows a lower correlation with geographic distance than migration matrices do. This difference can be attributed to the differing sensitivity of the methods for past migration events, and to genetic drift.

Low vitamin D status, high bone turnover, and bone fractures in centenarians.

The oldest olds, including centenarians, are increasing worldwide and, in the near future, will represent a consistent part of the population. We have studied bone status and metabolism in 104 subjects over 98 yr of age to evaluate possible interventions able to avoid fragility fractures and disability. Ninety females and 14 males not affected by any acute disease were considered. After a complete clinical assessment, blood was drawn for evaluating bone turnover markers, and performance tests together with skeletal ultrasonography (either at the phalanges or at the heel) were performed. We found that 38 subjects had sustained a total of 55 fractures throughout their lives, and 75% of these were fragility fractures. Twenty-eight fractures occurred at the proximal femur, with 14 after the age of 94 yr. Serum 25-hydroxyvitamin D was undetectable in 99 of 104 centenarians. PTH and serum C-terminal fragment of collagen type I were elevated in 64 and 90% of centenarians, respectively, with a trend toward hypocalcemia. Bone alkaline phosphatase levels were close to the upper limit. Serum IL-6 was elevated in 81% of centenarians and was positively correlated with PTH and negatively correlated with serum calcium. Serum creatinine was not correlated with PTH. Bone ultrasonography showed that most centenarians had low values, and ultrasonographic parameters were correlated with resorption markers. We conclude that the extreme decades of life are characterized by a pathophysiological sequence of events linking vitamin D deficiency, low serum calcium, and secondary hyperparathyroidism with an increase in bone resorption and severe osteopenia. These data offer a rationale for the possible prevention of elevated bone turnover, bone loss, and consequently the reduction of osteoporotic fractures and fracture-induced disability in the oldest olds through the supplementation with calcium and vitamin D.

The MALVA (MAntova LongeVA) study: an investigation on people 98 years of age and over in a province of Northern Italy.

The MALVA (MAntova LongeVA) study aims at investigating the socio-demographic, clinical and genetic characteristics of all subjects over 98 years of age residing in the province of Mantova (Northern Italy). In this paper we present the study protocol and the main demographic results. Absolute number, prevalence ratio and female/male ratio of the subjects aged 98+ and of the centenarians in the Mantova province (370,645 inhabitants at 31st December 1997) were checked at the baseline of the study (31st March 1998) as well as in the two years preceding and following the study. A total of 117 subjects aged 98+ (including 39 centenarians) were traced at 31st March 1998; the prevalence ratio was 31.6 per 100000 (12.1 for centenarians), and the female/male ratio was 6.3 (6.5 for centenarians). The distribution of the oldest old according to places of birth and residence was non-homogeneous across the provincial territory. Seventy-seven subjects (66% of the identified subjects) were enrolled in the study and administered a protocol including an interview about socio-economic conditions, lifetime habits and pathological and pharmacological case histories, as well as medical examination, performance-based tests and blood sample collection. Data on the socio-demographic characteristics and the health status of very old people in the province of Mantova are discussed and compared to findings from previous studies on Italian centenarians.

Genetic analysis of Paraoxonase (PON1) locus reveals an increased frequency of Arg192 allele in centenarians.

Human Paraoxonase (PON1) is a High-Density Lipoprotein (HDL)-associated esterase that hydrolyses lipo-peroxides. PON1 has recently attracted attention as a protective factor against oxidative modification of LDL and may therefore play an important role in the prevention of the atherosclerotic process. Two polymorphisms have been extensively studied: a Leucine (L allele) to Methionine (M allele) substitution at codon 55, and a Glutamine (A allele) to Arginine (B allele) substitution at codon 192. We have examined these two aminoacidic changes in 579 people aged 20 to 65 years old, and 308 centenarians. We found that the percentage of carriers of the B allele at codon 192 (B+ individuals) is higher in centenarians than in controls (0.539 vs 0.447), moreover we found that among the B+ individuals, the phenomenon was due to an increase of people carrying M alleles at codon 55 locus. In conclusion, we propose that genetic variability at PON1 locus affects survival at extreme advanced age.