Search

There is consistent evidence that immune response declines with aging, with wide interindividual variability and a still unclear relationship with the development of frailty. To address this question, we assessed the role of immune resilience (capacity to restore immune functions), operationalized as the neutrophil-to-lymphocytes ratio (NL-ratio) and monocytes-to-lymphocytes ratio (ML-ratio), in the pathway that from robust status shifts to pre-frailty and frailty, and finally to death. The InCHIANTI study enrolled representative samples from the registry lists of 2 towns in Tuscany, Italy. Baseline data were collected in 1998, with follow-up visits every 3 years. The 1 453 participants enrolled were assessed and followed for lifestyle, clinical condition, physical performance, clinical, and physiological measures. For the purpose of this analysis, we used only 1 022 subjects aged 65 or older at baseline. Participants in the 3 highest deciles of distribution for NL-ratio (>2.44) were more likely to experience a transition from robust to pre-frail, and to overt frailty status. Moreover, NL-ratio (tenth decile > 3.53) and ML-ratio (tenth decile > 2.02) were both predictors of mortality. These results were independent of chronological age, sex, comorbidities, and chronic low-grade inflammation assessed by high sensitivity C-reactive protein measurement. The 2 leucocytes-derived ratios, NL-ratio and ML-ratio, represent markers of immune resilience and predict changes in physical resilience and mortality. These biomarkers are inexpensive because they are based on data routinely collected in clinical practice and can be used to assess the risk of frailty progression and mortality. Clinical Trials Registration Number: NCT01331512 [ABSTRACT FROM AUTHOR]

Sarcopenia is characterized by skeletal muscle quantitative and qualitative alterations. A marker of collagen turnover, procollagen type III N-terminal peptide (P3NP), seems to be related to those conditions. This study aims to assess the predictive role of P3NP in muscle density and physical performance changes. In the InCHIANTI study, a representative sample from the registry lists of two towns in Tuscany, Italy, was recruited. Baseline data was collected in 1998, and follow-up visits were conducted every 3 years. Out of the 1453 participants enrolled at baseline, this study includes 1052 participants. According to P3NP median levels, population was clustered in two groups; 544 (51.7%) of the 1052 subjects included were classified in the low median levels (LM-P3NP); at the baseline, they were younger, had higher muscle density, and performed better at the Short Physical Performance Battery (SPPB), compared to the high-median group (HM-P3NP). LM-P3NP cases showed a lower risk to develop liver chronic diseases, CHF, myocardial infarction, and osteoarthritis. HM-P3NP levels were associated with a longitudinal reduction of muscle density, and this effect was potentiated by the interaction between P3NP and leptin. Moreover, variation in physical performance was inversely associated with high level of P3NP, and directly associated with high fat mass, and with the interaction between P3NP and muscle density. Our data indicate that P3NP is associated with the aging process, affecting body composition, physical performance, and clinical manifestations of chronic degenerative age-related diseases. [ABSTRACT FROM AUTHOR]

Aging adults experience increased health vulnerability and compromised abilities to cope with stressors, which are the clinical manifestations of frailty. Frailty is complex, and efforts to identify biomarkers to detect frailty and pre‐frailty in the clinical setting are rarely reproduced across cohorts. We developed a predictive model incorporating biological and clinical frailty measures to identify robust biomarkers across data sets. Data were from two large cohorts of older adults: "Invecchiare in Chianti (Aging in Chianti, InCHIANTI Study") (n = 1453) from two small towns in Tuscany, Italy, and replicated in the Atherosclerosis Risk in Communities Study (ARIC) (n = 6508) from four U.S. communities. A complex systems approach to biomarker selection with a tree‐boosting machine learning (ML) technique for supervised learning analysis was used to examine biomarker population differences across both datasets. Our approach compared predictors with robust, pre‐frail, and frail participants and examined the ability to detect frailty status by race. Unique biomarker features identified in the InCHIANTI study allowed us to predict frailty with a model accuracy of 0.72 (95% confidence interval (CI) 0.66–0.80). Replication models in ARIC maintained a model accuracy of 0.64 (95% CI 0.66–0.72). Frail and pre‐frail Black participant models maintained a lower model accuracy. The predictive panel of biomarkers identified in this study may improve the ability to detect frailty as a complex aging syndrome in the clinical setting. We propose several concrete next steps to keep research moving toward detecting frailty with biomarker‐based detection methods. [ABSTRACT FROM AUTHOR]

Background: Neutrophils and lymphocytes represent the larger percentage of all white blood cells, they vary with age, with a progressive increase of the ratio in the first years of life, and then tend to remain at similar levels in steady state condition during adult age. Neutrophils to lymphocytes-ratio (NL-ratio) was proposed as an effective and low-cost marker to monitor and predict the evolution of several clinical conditions. The main objective of the study is to analyze its temporal trend variation, over twenty years' follow-up, according to age, sex, and main clinical diagnosis, in a large representative Italian population. Methods: The InCHIANTI study enrolled representative samples from the registry list of two towns in Tuscany, Italy. Baseline data were collected in 1998, and last follow-up visits were made in 2015-18. 1343 out of the 1453 participants enrolled were included, and consented to donate a blood sample. All subjects were assessed and followed for life-style, clinical condition, physical performance, and underwent an instrumental diagnostic session. Results: The NL-ratio showed a statistically significant interaction between birth-cohort and time of the study (p-value = 0.005). A gender dimorphism was recognized in the neutrophils absolute count and in the NL-ratio. Moreover, in female participants only, those who reported CHF had lower neutrophil-count and NL-ratio; whereas an increase in creatinine clearance was directly associated with NL-ratio. In male subjects, an increase of BMI was inversely associated with both NL-ratio and neutrophils-count during the follow-up; a similar association but in the opposite direction was observed in female participants. Conclusion: NL-ratio is a more reliable predictor of healthy aging than absolute lymphocytes and/or neutrophils counts. It is associated with the changes induced by disease, lifestyle, and environmental challenges in the immune system. NL-ratio confirms the gender dimorphism in the occurrence of inflammation-driven diseases, thus providing additional evidence for the necessity of tailored sex-specific measures to prevent and treat such diseases. [ABSTRACT FROM AUTHOR]

Background: In general, plant protein intake was inversely associated with mortality in studies in middle-aged adults. Our aim was to evaluate the long-term associations of animal and plant protein intake with mortality in older adults.Methods: A prospective cohort study including 1 139 community-dwelling older adults (mean age 75 years, 56% women) living in Tuscany, Italy, followed for 20 years (InCHIANTI study) was analyzed. Dietary intake by food frequency questionnaires and clinical information were assessed 5 times during the follow-up. Protein intakes were expressed as percentages of total energy. Time-dependent Cox regression models adjusted for confounders were used to assess the association between plant and animal protein intake, and mortality.Results: During the 20 years of follow-up (mean: 12 years), 811 deaths occurred (292 of cardiovascular- and 151 of cancer-related causes). Animal protein intake was inversely associated with all-cause (hazard ratio [HR] per 1% of total energy from protein increase, 95% confidence interval [CI]: 0.96, 0.93-0.99) and cardiovascular mortality (HR per 1% of total energy from protein increase, 95% CI: 0.93, 0.87-0.98). Plant protein intake showed no association with any of the mortality outcomes, but an interaction with baseline hypertension was found for all-cause and cardiovascular mortality (p < .05).Conclusions: Animal protein was inversely associated with all-cause and cardiovascular mortality in older adults. Further studies are needed to provide recommendations on dietary protein intake for older adults. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the relationship between gait speed, recall memory, and mortality. Design A cohort study (last follow-up December 2009). Setting Tuscany, Italy. Participants Individual data from 1,014 community-dwelling older adults aged 60 years or older with baseline gait speed and recall memory measurements and follow-up for a median time of 9.10 ( IQR 7.1;9.3) years. Participants were a mean ( SD) age of 73.9 (7.3) years, and 55.8% women. Participants walking faster than 0.8 m/s were defined as fast walkers; good recall memory was defined as a score of 2 or 3 in the 3-word delayed recall section of the Mini-Mental State Examination. Measurements All-cause mortality. Results There were 302 deaths and the overall 100 person-year death rate was 3.77 (95% CI: 3.37-4.22). Both low gait speed and poor recall memory were associated with mortality when analysed separately ( HR = 2.47; 95% CI: 1.87-3.27 and HR = 1.47; 95% CI: 1.16-1.87, respectively). When we grouped participants according to both recall and gait speed, death rates (100 person-years) progressively increased from those with both good gait speed and memory (2.0; 95% CI: 1.6-2.5), to those with fast walk but poor memory (3.4; 95% CI: 2.8-4.2), to those with slow walk and good memory (8.8; 95% CI: 6.4-12.1), to those with both slow walk and poor memory (13.0; 95% CI: 10.6-16.1). In multivariate analysis, poor memory significantly increases mortality risk among persons with fast gait speed ( HR = 1.40; 95% CI: 1.04-1.89). Conclusion In older persons, gait speed and recall memory are independent predictors of expected survival. Information on memory function might better stratify mortality risk among persons with fast gait speed. [ABSTRACT FROM AUTHOR]

Background. The aging-suppressor gene klotho encodes a single-pass transmembrane protein that in mice is known to extend life span when overexpressed and resemble accelerated aging when expression is disrupted. It is not known whether there is a relationship between plasma levels of secreted klotho protein and longevity in humans. Methods. We measured plasma klotho in 804 adults, greater than or equal to 65 years, in the InCHIANTI study, a longitudinal population-based study of aging in Tuscany, Italy. Results. During 6 years of follow-up, 194 (24.1%) of the participants died. In a multivariate Cox proportional hazards model, adjusting for age, sex, education, body mass index, physical activity, total cholesterol, high-density lipoprotein cholesterol, cognition, 25-hydroxyvitamin D, parathyroid hormone, serum calcium, mean arterial pressure, and chronic diseases, participants in the lowest tertile of plasma klotho (<575 pg/mL) had an increased risk of death compared with participants in the highest tertile of plasma klotho (>763 pg/mL; hazards ratio 1.78, 95% confidence interval 1.20–2.63). Conclusions. In older community-dwelling adults, plasma klotho is an independent predictor of all-cause mortality. Further studies are needed to elucidate the potential biological mechanisms by which circulating klotho could affect longevity in humans. [ABSTRACT FROM PUBLISHER]

OBJECTIVES: To investigate the characteristics of older adults who develop high interleukin-6 (IL-6) levels at 3-year follow-up. DESIGN: Population-based study of adults living in Tuscany, Italy. SETTING: Community. PARTICIPANTS: Adults aged 65 and older and were selected for this study. Of 1,155 baseline participants aged 65 and older, 741 had IL-6 measurements at baseline and 3-year follow-up. MEASUREMENTS: The uppermost quartile of IL-6 was used as the threshold for defining high IL-6 (≥4.18 pg/mL). Serum IL-6 levels were assessed using enzyme immunoassay. RESULTS: Of the 581 participants with IL-6 levels less than 4.18 pg/mL at baseline, 106 (18.2%) had developed high IL-6 at follow-up. Although women had lower IL-6 levels at baseline than men, the risk of developing high IL-6 did not differ according to sex. High adiposity, defined as a body mass index of 30.0 kg/m2 or higher (odds ratio (OR)=2.63, 95% confidence interval (CI)=1.40–4.96), and large waist circumference, defined as 102 cm or greater for men and 88 cm or greater for women (OR=2.05, 95% CI=1.24–3.40), were significant predictors of developing high IL-6 at follow-up. Other significant predictors were presence of three or more chronic diseases (OR=3.66, 95% CI=1.54–8.70), higher baseline IL-6 (OR=1.82, 95% CI=1.39–2.38) and higher white blood cell count (OR=1.24, 95% CI=1.06–1.45). Faster walking speed associated with decreased risk of progressing to elevated IL-6 (OR=0.83, 95% CI=0.74–0.92). CONCLUSION: Older age, greater adiposity, slower walking speed, higher disease burden, and higher white blood cell count were associated with greater risk of IL-6 elevation over a 3-year period. Future research should target older adults with these characteristics to prevent progression to a proinflammatory state. [ABSTRACT FROM AUTHOR]

Aims: We examined the relationship between plasma selenium levels at enrollment and all-cause mortality over a 6-year period among participants in the InCHIANTI study. Methods. 1042 men and women ≥65 years from the InCHIANTI study, a population- based study of older adults living in the Chianti region of Tuscany, a population-based cohort in Tuscany, Italy. Plasma selenium was measured at enrollment (1998-2000), and vital status was ascertained until May 2006. Results: During follow-up, 237 participants (22. 7%) died. At enrollment, mean (SD) plasma selenium concentrations among participants who survived or died were 0.96 (0.14) and 0.87 (0.18)µmol/L (p<0.0001), respectively. The proportion of participants who died, from lowest to highest quartile of selenium, was 41.3, 27.0, 18.1 and 13.5% (p<0.0001 by Mantel-Haenszel chi-square). After adjusting for age, sex, education, and chronic diseases, adults in the lowest quartile of plasma selenium at enrollment had higher mortality compared with those in the highest quartile (Hazard Ratio (HR) 1.60, 95% Confidence Interval (CI) 1.04-2.47, p=0.034). Conclusion: Low plasma selenium may be an independent predictor of mortality among older adults living in the community. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To describe a set of complex walking tasks (CWTs) that can be used to evaluate mobility and to characterize age- and sex-specific performance on these tests. DESIGN: A population-based study of persons living in the Chianti geographic area (Tuscany, Italy). SETTING: Community. PARTICIPANTS: One thousand two hundred twenty-seven persons (aged 20–95) selected from the city registries of Greve and Bagno a Ripoli (Tuscany, Italy). MEASUREMENTS: Gait velocity (m/s) was measured during 13 walking tests (Walking InCHIANTI Toolkit (WIT)) used to examine walking ability under a range of conditions and distances. Other measures included performance on the Short Physical Performance Battery and self-reported health and functional status, including disability in activities of daily living. RESULTS: Age-associated differences on the WIT were reflected in the number of older adults unable to complete CWTs and a decrease in gait velocity. For all tasks, decrements in walking speed with increasing age were significantly larger at aged 65 and older. Performance on CWTs was highly variable and could not be explained by usual gait speed measured under low-challenge conditions alone. CONCLUSION: CWTs may provide important insight into mobility function, particularly in persons with normal or near-normal usual gait speed. Further research is needed to elucidate the specific physiological mechanisms that contribute to declining performance on CWT with increasing age. [ABSTRACT FROM AUTHOR]

The purpose of the study was to provide information on dietary intake in the InCHIANTI study population, a representative sample (n = 1453) of persons living in two towns of Tuscany (Italy), including a large number of old and very old individuals (79.5% >65 y old). We also investigated whether difficulties in nutrition-related activities were associated with inadequate intake of selected nutrients. The percentage of persons with an inadequate intake of nutrients according to Italian Recommended Nutrients Levels (LARN) was higher in the older age groups. Older persons tended to adapt their diets in response to individual functional difficulties, often leading to monotonous food consumption and, as a consequence, to inadequate nutrient intakes. Multiple logistic models were used to evaluate whether inadequate intake of selected nutrients could be predicted by nutrition-related difficulties. Reporting difficulties in three or more nutrition-related activities (chewing, self-feeding, shopping for basic necessities, carrying a shopping bag, cooking a warm meal, using fingers to grasp or handle) significantly increased the risk of inadequate intake of energy [odds ratio (OR) = 3.8, 95% CI = 1.9-7.8) and vitamin C (OR = 2.2, 95% CI = 1.2-4.2, after adjustment for energy intake). More attention to functional problems in the elderly population and the provision of formal or informal help to those who have difficulty in purchasing, processing and eating food may reduce, at least in part, the percentage of older persons with poor nutrition. [ABSTRACT FROM AUTHOR]

Abstract: We examined whether adherence to a Mediterranean-style diet has positive effects on mobility assessed over a 9-year follow-up in a representative sample of older adults. This research is part of the InCHIANTI Study, a prospective population-based study of older persons in Tuscany, Italy. The sample for this analysis included 935 women and men aged 65years and older. Adherence to the Mediterranean diet was assessed at baseline by the standard 10-unit Mediterranean diet score (MDS). Lower extremity function was measured at baseline, and at the 3-, 6- and 9-year follow-up visits using the short physical performance battery (SPPB). At baseline, higher adherence to Mediterranean diet was associated with better lower body performance. Participants with higher adherence experienced less decline in SPPB score, which was of 0.9 points higher (p <.0001) at the 3-year-follow, 1.1 points higher (p =0.0004) at the 6-year follow-up and 0.9 points higher (p =0.04) at the 9-year follow-up compared to those with lower adherence. Among participants free of mobility disability at baseline, those with higher adherence had a lower risk (HR=0.71, 95% CI=0.51–0.98, p =0.04) of developing new mobility disability. High adherence to a Mediterranean-style diet is associated with a slower decline of mobility over time in community-dwelling older persons. If replicated, this observation is highly relevant in terms of public health. [Copyright &y& Elsevier]