No abstract

Among nonagenarians and centenarians in three different European regions, we found a significant North-South gradient in handgrip strength with substantially lower values in Calabria. This finding may be due both to population background differences (e.g., genetic variations, birth weight, childhood growth) and to sociocultural differences (e.g., lifestyle, health care).

Urinary incontinence (UI) is very common in the elderly and has personal and social implications. Many authors have pointed out the necessity to analyze UI in correlation with the overall quality of aging, to better understand this syndrome and define measures for its prevention and treatment. In the present study, we addressed this problem by analyzing the UI correlation with frailty, which has emerged in the last decade as the geriatric syndrome correlated with individual homeostatic capacity and then as the basis of the age-related physical decline. In addition, the monitoring of our sample for a long period allowed us to estimate the prognostic significance of UI by analyzing the correlation between UI and mortality. The analysis was performed in a large sample that included numerous ultra-nonagenarians, a population segment that is still poorly known for UI and other geriatric parameters. We found a strict correlation between UI and frailty, suggesting that UI is correlated to the homeostatic and physiological decline leading to frailty. In addition, we found that UI is an independent mortality risk factor in ultra-nonagenarians, suggesting that the neurological sensitivity needed to be continent is lost very soon when the frailty associated physiological decline begins. On the whole, our study suggests that UI is a marker of frailty and that UI patients should be monitored and, in case, treated in a timely manner to avoid, or to limit, the effects of frailty such as malnutrition, falls, and the consequent accumulation of disabilities.

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.

The description of frailty, a syndrome of the elderly due to the decline of homeostatic capacities, has opened new opportunities in the study of the biological basis of human aging. However, the noticeable heterogeneity for this trait in different geographic areas makes it difficult to use standardized methods for measuring the quality of aging in different populations. Consequently, the necessity to carry out population-specific surveys to define tools which are able to highlight groups of subjects with homogeneous aging phenotype within each population has emerged. We carried out an extensive monitoring of the status of the elderly population in Calabria, southern Italy, performing a geriatric multidimensional evaluation of 680 subjects (age range 65-108 years). Then, in order to classify the subjects, we applied a cluster analysis which considered physical, cognitive, and psychological parameters such as classification variables. We identified groups of subjects homogeneous for the aging phenotypes. The diagnostic and predictive soundness of our classification was confirmed by a 3-year longitudinal study. In fact, both Kaplan-Meier estimates of the survival functions and Cox proportional hazard models indicate higher survival chance for subjects characterized by lower frailty. The availability of operative frailty phenotypes allows a reappraisal of the biological basis of healthy aging as it regards both biomarkers correlated with the frail phenotype and the genetic variability associated with the phenotypes identified. Indeed, we found that the frailty phenotype is strongly correlated with clinical parameters associated with the nutritional status.

Background: several studies suggest that a decreased thyroid activity might be favourable in oldest-old subjects and that subclinical thyroid hyperfunction may be detrimental.Objectives: to verify whether declining levels of circulating thyroid hormones may contribute to longevity.Design: cross-sectional observational study.Setting: all subjects were born in Calabria (southern Italy) and their ancestry in the region was ascertained up to the grandparents.Subjects: six hundred and four home-dwelling subjects (301 females, 303 males), divided into three groups: 278 individuals 60–85 years old; 179 children or nieces/nephews of centenarians who are 60–85 years old; 147 individuals older than 85 years.Methods: thyroid function parameters were measured in the frame of a comprehensive geriatric assessment.Results: FT3 and FT4 levels were negatively associated with age. Lower levels of FT3, FT4 and TSH were found in centenarians’ children and nieces/nephews with respect to age-matched controls. Indeed, being a relative of centenarians qualified as an independent correlate of thyroid parameters.Conclusions: age-related subtle thyroid hypofunction (either due to a familial component or due to a reset of the thyroid function occurring between the sixth and the eighth decade of life) appears to be related to longevity.

The definition of a precise and consistent aging phenotype that allows to measure the physical and cognitive decline, as well as the increase of mortality hazard late in life, is a major problem for studies aimed at finding the genetic factors modulating rate and quality of human aging. In this frame, it seems promising the concept of frailty which tends to figure out the subjects who are more vulnerable and more prone to negative outcomes, such as death or hospitalization. Cognitive, functional and psychological measures turned out to be the most effective measures to define frailty, as they condense most of the frailty cycle that occurs in the elderly and is probably responsible of the aging related physical decline. We used MMSE, Hand Grip strength, and GDS as variable parameters in a hierarchical Cluster Analysis (CA) in order to recognise aging phenotypes. By using a sample of 65-85 years old subjects we identified three frailty phenotypes that were consistent from both geriatric and genetic perspectives. Therefore, the method we propose may provide unbiased phenotypes suitable for the identification of genetic variants affecting the quality of aging in this age range. The CA method was less effective in ultranonagenarians, probably due to the high prevalence of frail subjects in this age group that makes difficult to distinguish discrete phenotypes.

SummaryThe genes coding for apolipoprotein A1 (APOA1 ), apolipoprotein C3 (APOC3 ) and apolipoprotein A4 (APOA4 ) are tandemly organised within a short region on chromosome 11q23-q24. Polymorphisms of these genes have been extensively investigated in lipoprotein disorders and cardiovascular diseases, but poorly investigated in healthy ageing. The aim of this study was to describe possible modifications of the APOA1, APOC3, and APOA4 gene pool by cross-sectional studies carried out in a healthy ageing population whose ages ranged from 18 to 109 years (800 subjects, 327 males and 473 females, free of clinically manifested disease, and with emato-chemical parameters in the norm). APOA1-MspI-RFLP (−75 nt from the transcription starting site), APOC3-SstI-RFLP (3 UTR, 3238 nt), and APOA4-HincII-RFLP (Asp 127 /Ser 127 ) were analysed according to age and sex. A significant agerelated variation of the APOA1 gene pool was observed in males. An analysis of the allele average effect exerted by APOA1-MspI-RFLP A/P alleles (Absence/Presence of the restriction site) on lipidemic parameters in 46-80 year old males showed that allele A decreased, while allele P significantly increased, serum LDL-cholesterol. Unexpectedly, the P allele was over-represented in the group of the oldest old subjects, thus giving evidence of another "genetic paradox of centenarians".