Glomerular filtration rate in the elderly and in the oldest old: correlation with frailty and mortality.

The equations for estimating kidney function have become very popular in the last decade. However, the clinical and prognostic meaning of these measures may be very different in older populations. Two cohorts of people aged 65-89 years (older sample) and 90 or more (oldest old sample) were used to investigate the prognostic significance of estimated glomerular filtration rate (eGFR). Additionally, we also investigated whether combining frailty and eGFR may improve the accuracy of frailty in predicting mortality. We found that lower eGFR values were significantly more frequent among frail subjects in both groups. eGFR < 30 was associated with increased risk for all-cause mortality either in subjects aged 65-89 years (HR = 3.71, 95% CI = 1.23-11.2) or in those aged 90 or more (HR = 1.53, 95% CI = 1.05-2.23). In the latter group, a not significant trend for increasing mortality was also observed among people with eGFR > 60 (HR = 1.28, 95% CI = 0.72-2.26). In addition, the oldest old subjects with eGFR > 60 and eGFR < 30 had the lowest hand-grip strength and ADL values. Combining eGFR and frailty status significantly improved the accuracy of frailty in predicting mortality only in the older sample. In conclusion, a U-shaped relationship exists between eGFR and mortality in the oldest old, but not in older individuals. Our findings suggest that eGFR needs to be adjusted for muscle mass/physical performance when estimating kidney function in people aged 90 or more. Nevertheless, in subjects aged 65-89 years, eGFR may improve the accuracy of frailty status in predicting prognosis, thus suggesting that eGFR may represent an additional dimension of frailty syndrome.

How to classify the oldest old according to their health status: a study on 1160 subjects belonging to 552 90+ Italian sib-ships characterized by familial longevity recruited within the GEHA EU Project.

The health status of the oldest old, the fastest increasing population segment worldwide, progressively becomes more heterogeneous, and this peculiarity represents a major obstacle to their classification. We compared the effectiveness of four previously proposed criteria (Franceschi et al., 2000; Evert et al., 2003; Gondo et al., 2006; Andersen-Ranberg et al., 2001) in 1160 phenotypically fully characterized Italian siblings of 90 years of age and older (90+, mean age: 93 years; age range: 90-106 years) belonging to 552 sib-ships, recruited in Northern, Central and Southern Italy within the EU-funded project GEHA, followed for a six-year-survival. Main findings were: (i) "healthy" subjects varied within a large range, i.e. 5.2% (Gondo), 8.7% (Evert), 17.7% (Franceschi), and 28.5% (Andersen-Ranberg); (ii) Central Italy subjects showed better health than those from Northern and Southern Italy; (iii) mortality risk was correlated with health status independently of geographical areas; and (iv) 90+ males, although fewer in number, were healthier than females, but with no survival advantage. In conclusion, we identified a modified version of Andersen-Ranberg criteria, based on the concomitant assessment of two basic domains (cognitive, SMMSE; physical, ADL), called "Simple Model of Functional Status" (SMFS), as the most effective proxy to distinguish healthy from not-healthy subjects. This model showed that health status was correlated within sib-ships, suggesting a familial/genetic component.

Urinary incontinence in the elderly and in the oldest old: correlation with frailty and mortality.

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.

To grow old in southern Italy: a comprehensive description of the old and oldest old in Calabria.

BACKGROUND: The unprecedented growth of the elderly population is posing important social and medical problems as management of this population is highly demanding in terms of assistance and care. Consequently, many studies are focusing on the elderly subjects in order to better understand their needs by identifying various environmental, social, psychological, and genetic factors determining the quality of ageing. OBJECTIVES: Our aim was to carry out a survey of the elderly Calabrian population in order to highlight the social and medical conditions of this continuously growing population group. METHODS: We have been monitoring the elderly population of Calabria for more than 10 years. For the present study, we collected data regarding 853 subjects by using two specific questionnaires, one for the subjects older than 90 years (400 subjects) and one for the subjects aged between 65 and 85 years (453 subjects). RESULTS: The survey allowed us to carry out an extensive description of the ageing Calabrian population regarding the sociodemographic characteristics, living conditions, cognitive functioning, level of independence in activities of daily living, former and current diseases and health disorders. We could notice that males were in a better condition than females. In fact, male subjects turned out to have better physical performance and lower comorbidity, although their life expectancy is lower. Ultranonagenarians had a lower incidence of serious diseases (such as diabetes, osteoporosis and gastric ulcer), but a higher incidence of non-fatal chronic, debilitating conditions (cataract and bronchitis among others). CONCLUSION: The data we collected and analyzed offer a portrait of elderly Calabrian subjects, on who they are, how they feel, which social and psychological resources they have, and what their health status is. Analysis of the data highlighted that they are characterized by a lower physical performance in comparison to other European populations. Finally, the data presented here may also serve as a valuable source of information to characterize the ageing Calabrian population and improve the care of these subjects.

A cross-section analysis of FT3 age-related changes in a group of old and oldest-old subjects, including centenarians' relatives, shows that a down-regulated thyroid function has a familial component and is related to longevity.

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.

A novel, population-specific approach to define frailty.

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.

Handgrip strength among nonagenarians and centenarians in three European regions.

BACKGROUND: Handgrip strength is an important predictor of disability and mortality among old people. The aim was to compare the grip strength among very old people in three regions of Europe. METHODS: In this substudy of the European Challenge for Healthy Aging project, only the long-lived probands were included. The maximum value of three measurements of handgrip strength was selected for the analysis. Adjustment for factors known to be correlated with grip strength was made by linear regression. RESULTS: Among 598 very old people (median age = 98 years) a clear North-South gradient was observed: For men, handgrip strength dropped from 24.2 kg in Southern Denmark to 20.8 kg in Languedoc-Roussillon, France and 14.2 kg in Calabria, Italy (p < .0001), whereas for women the drop was smaller (from 12.2 to 9.2 kg; p = .0021). The difference remains significant after adjustment for age, gender, housing, knee height, Activities of Daily Living (ADL) scale score, score on the Six-Item Mini-Mental State Examination, chair stand, and number of age-related diseases, although these factors explain two thirds of the variation in handgrip strength. CONCLUSIONS: 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).

A study of the average effect of the 3'APOB-VNTR polymorphism on lipidemic parameters could explain why the short alleles (<35 repeats) are rare in centenarians.

BACKGROUND: In studies on the genetics of human aging, we observed an age-related variation of the 3'APOB-VNTR genotypic pool (alleles: Short, S, <35 repeats; Medium, M, 35-39 repeats; Long, L, >39 repeats) with the homozygous SS genotype showing a convex frequency trajectory in a healthy aging population. This genotype was rare in centenarians, thus indicating that the S alleles are unfavorable to longevity, while common in adults, thus indicating a protective role at middle age. This apparent paradox could be due to possible effects exerted by the above polymorphism on lipidemic parameters. Aim of the work was to get insights into these puzzling findings METHODS: We followed a double strategy. Firstly, we analyzed the average effects of S (alphaS), M (alphaM), and L (alphaL) alleles on lipidemic parameters in a sample of healthy people (409 subjects aged 20-102 years) recruited in Calabria (southern Italy). The (alphaS), (alphaM), and (alphaL) values were estimated by relating 3'APOB-VNTR genotypes to lipidemic parameters, after adjustment for age, sex and body mass index (multiple regression). Then, we analyzed the S alleles as susceptibility factors of Cardiovascular Atherosclerotic Disease (CD) in CD patients characterized either by low serum HDL-Cholesterol or by high serum LDL-Cholesterol (CD-H and CD-L patients, 40 and 40 subjects respectively). The Odds Ratios (OR) were computed for carriers of S alleles in CD-H and CD-L patients matched for origin, sex and age with controls extracted from the sample of healthy subjects. RESULTS: By the analysis of the healthy sample group we found that the S alleles lower the average values of serum Total Cholesterol (alphaS = -5.98 mg/dL with [-11.62/-0.74] 95% confidence interval) and LDL-Cholesterol (alphaS = -4.41 mg/dL with [-8.93/-0.20] 95% confidence interval) while the alleles M and L have no significant effect on the lipidemic phenotype. In line with these findings, the analysis of CD patients showed that the S alleles are protective as for CD-L (O.R. = 0.55 with [0.21/0.98] 95% confidence interval) while neutral as for CD-H (O.R. = 0.75 with [0.32/1.60] 95% confidence interval). CONCLUSION: On the whole, the S alleles would be advantageous in adults (by protecting from CD-L) while dangerous in the elderly, probably by lowering serum cholesterol below a critical threshold. This could explain the convex frequency trajectory of SS genotypes previously observed in a healthy aging population.

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.