Exceptional Parental Longevity Associated with Lower Risk of Alzheimer's Disease and Memory Decline

OBJECTIVES: To determine whether offspring of parents with exceptional longevity (OPEL) have a lower rate of dementia than offspring of parents with usual survival (OPUS). DESIGN: Community‐based prospective cohort study. SETTING: Bronx, New York. PARTICIPANTS: A volunteer sample of 424 community‐residing older adults without dementia aged 75 to 85 recruited from Bronx County starting in 1980 and followed for up to 23 years. MEASUREMENTS: Epidemiological, clinical, and neuropsychological assessments were completed every 12 to 18 months. OPEL were defined as having at least one parent who reached the age of at least 85. OPUS were those for whom neither parent reached the age of 85. Dementia was diagnosed according to case conference consensus based on Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised, criteria without access to information on parental longevity. Alzheimer's disease was diagnosed using established criteria. RESULTS: Of 424 subjects, 149 (35%) were OPEL, and 275 (65%) were OPUS. Mean age at entry for both groups was 79. The OPEL group had a lower incidence of Alzheimer's disease (hazard ratio=0.57, 95% confidence interval=0.35–0.93). After adjusting for sex, education, race, hypertension, myocardial infarction, diabetes mellitus, and stroke, results were essentially unchanged. OPEL also had a significantly lower rate of memory decline on the Selective Reminding Test (SRT) than OPUS (P=.03). CONCLUSION: OPEL develop dementia and Alzheimer's disease at a significantly lower rate than OPUS. Demographic and medical confounders do not explain this result. Factors associated with longevity may protect against dementia and Alzheimer's disease.     

Lipid metabolism in long-lived families: the Leiden Longevity Study

Mechanisms underlying the variation in human life expectancy are largely unknown, but lipid metabolism and especially lipoprotein size was suggested to play an important role in longevity. We have performed comprehensive lipid phenotyping in the Leiden Longevity Study (LLS). By applying multiple logistic regression analysis we tested for the first time the effects of parameters in lipid metabolism (i.e., classical serum lipids, lipoprotein particle sizes, and apolipoprotein E levels) on longevity independent of each other. Parameters in lipid metabolism were measured in offspring of nonagenarian siblings from 421 families of the LLS (n = 1,664; mean age, 59 years) and in the partners of the offspring as population controls (n = 711; mean age, 60 years). In the initial model, where lipoprotein particles sizes, classical serum lipids and apolipoprotein E were included, offspring had larger low-density lipoprotein (LDL) particle sizes (p = 0.017), and lower triglyceride levels (p = 0.026), indicating that they displayed a more beneficial lipid profile. After backwards regression only LDL size (p = 0.014) and triglyceride levels (p = 0.05) were associated with offspring from long-lived families. Sex-specific backwards regression analysis revealed that LDL particle sizes were associated with male longevity (increase in log odds ratio (OR) per unit = 0.21; p = 0.023). Triglyceride levels (decrease OR per unit = 0.22; p = 0.01), but not LDL particle size, were associated with female longevity. Due to the analysis of a comprehensive lipid profile, we confirmed an important role of lipid metabolism in human longevity, with LDL size and triglyceride levels as major predicting factors.     

Effect of age on in vivo oxidative capacity in two locomotory muscles of the leg

To determine the effects of age and sex on in vivo mitochondrial function of distinct locomotory muscles, the tibialis anterior (TA) and medial gastrocnemius (MG), of young (Y; 24 ± 3 years) and older (O; 69 ± 4) men (M) and women (W) of similar overall physical activity (PA) was compared. In vivo mitochondrial function was measured using phosphorus magnetic resonance spectroscopy, and PA and physical function were measured in all subjects. Overall PA was similar among the groups, although O (n = 17) had fewer daily minutes of moderate-to-vigorous PA (p = 0.001), and slowed physical function (p < 0.05 for all variables), compared with Y (n = 17). In TA, oxidative capacity (V_max; mM s⁻¹) was higher in O than Y (p < 0.001; Y = 0.90 ± 0.12; O = 1.12 ± 0.18). There was no effect of age in MG (p = 0.5; Y = 0.91 ± 0.17; O = 0.96 ± 0.24), but women had higher oxidative capacity than men (p = 0.007; M = 0.84 ± 0.18; W = 1.03 ± 0.18). In vivo mitochondrial function was preserved in healthy O men and women, despite lower intensity PA and physical function in this group. The extent to which compensatory changes in gait may be responsible for this preservation warrants further investigation. Furthermore, women had higher oxidative capacity in the MG, but not the TA.     

Linkage and association of successful aging to the 6q25 region in large Amish kindreds

Successful aging (SA) is a multidimensional phenotype involving living to older age with high physical function, preserved cognition, and continued social engagement. Several domains underlying SA are heritable, and identifying health-promoting polymorphisms and their interactions with the environment could provide important information regarding the health of older adults. In the present study, we examined 263 cognitively intact Amish individuals age 80 and older (74 SA and 189 “normally aged”) all of whom are part of a single 13-generation pedigree. A genome-wide association study of 630,309 autosomal single nucleotide polymorphisms (SNPs) was performed and analyzed for linkage using multipoint analyses and for association using the modified quasi-likelihood score test. There was evidence for linkage on 6q25-27 near the fragile site FRA6E region with a dominant model maximum multipoint heterogeneity LOD score = 3.2. The 1-LOD-down support interval for this linkage contained one SNP for which there was regionally significant evidence of association (rs205990, p = 2.36 × 10⁻⁵). This marker survived interval-wide Bonferroni correction for multiple testing and was located between the genes QKI and PDE10A. Other areas of chromosome 6q25-q27 (including the FRA6E region) contained several SNPs associated with SA (minimum p = 2.89 × 10⁻⁶). These findings suggest potentially novel genes in the 6q25-q27 region linked and associated with SA in the Amish; however, these findings should be verified in an independent replication cohort.

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The online version of this article (doi:10.1007/s11357-012-9447-1) contains supplementary material, which is available to authorized users.     

Relationship between vitamin D and inflammatory markers in older individuals

In older persons, vitamin D insufficiency and a subclinical chronic inflammatory status frequently coexist. Vitamin D has immune-modulatory and in vitro anti-inflammatory properties. However, there is inconclusive evidence about the anti-inflammatory role of vitamin D in older subjects. Thus, we investigated the hypothesis of an inverse relationship between 25-hydroxyvitamin D (25(OH)D) and inflammatory markers in a population-based study of older individuals. After excluding participants with high-sensitivity C-reactive protein (hsCRP) ≥ 10 mg/dl and those who were on chronic anti-inflammatory treatment, we evaluated 867 older adults ≥65 years from the InCHIANTI Study. Participants had complete data on serum concentrations of 25(OH)D, hsCRP, tumor necrosis factor (TNF)-α, soluble TNF-α receptors 1 and 2, interleukin (IL)-1β, IL-1 receptor antagonist, IL-10, IL-18, IL-6, and soluble IL-6 receptors (sIL6r and sgp130). Two general linear models were fit (model 1—adjusted for age, sex, and parathyroid hormone (PTH); model 2—including covariates of model 1 plus dietary and smoking habits, physical activity, ADL disability, season, osteoporosis, depressive status, and comorbidities). The mean age was 75.1 ± 17.1 years ± SD. In model 1, log(25OH-D) was significantly and inversely associated with log(IL-6) (β ± SE = −0.11 ± 0.03, p = <0.0001) and log (hsCRP) (β ± SE = −0.04 ± 0.02, p = 0.04) and positively associated with log(sIL6r) (β ± SE = 0.11 ± 0.04, p = 0.003) but not with other inflammatory markers. In model 2, log (25OH-D) remained negatively associated with log (IL-6) (β ± SE = −0.10 ± 0.03, p = 0.0001) and positively associated with log(sIL6r) (β ± SE = 0.11 ± 0.03, p = 0.004) but not with log(hsCRP) (β ± SE = −0.01 ± 0.03, p = 0.07). 25(OH)D is independently and inversely associated with IL-6 and positively with sIL6r, suggesting a potential anti-inflammatory role for vitamin D in older individuals.     

Hormonal determinants and effect of ER22/23EK glucocorticoid receptor gene polymorphism on health status deterioration in the participants of the Mataró Ageing Study

The purpose of this study is to assess the potential relationships of circulating IGF-I, adrenal and gonadal steroids, and polymorphism ER22/23EK of the glucocorticoid receptor (GC-R) gene with nutritional, functional and cognitive deterioration in a group of elderly people living independently. This is a population-based prospective study with 313 individuals (160 women and 153 men, 76.7 ± 7 years) who participated. A physical exam, evaluation of functional capacity (Barthel scale), cognitive function (mini-mental state examination-MMSE), geriatric depression scale (GDS), mininutritional assessment (MNA-SF) and cardiometabolic status were performed at basal time point and at 2 years of follow-up. Biological measurements included cortisol, dehydroepiandrosterone (DHEA), DHEA sulphate, testosterone, estradiol, IGF-I and polymorphism ER22/23EK of the GC-R gene. Estradiol was associated with MNA-SF decrease over time (p < 0.01, adjusted for age and gender, beta = −0.17, p = 0.03). Weight loss was related to testosterone in men (8.6 vs 12.1 pg/ml in no losers; p = 0.03), and in women with GDS (13.0% with depression vs 3.3% with no depression; p = 0.05) and MMSE (22.2% with cognitive deterioration vs 4.8% with no cognitive deterioration; p = 0.049). Barthel decrease was associated with testosterone (p = 0.02, after adjusting for age and gender, beta = −0.520, p < 0.001), and SHBG (p < 0.01, adjusted for age and gender, beta = 0.18, p < 0.01). DHEA was associated with deterioration in the MMSE (p = 0.01, after adjusting for age, gender, GDS scale and academic status, beta = −0.26, p = 0.01). Frailty development was related only in men with testosterone levels at the beginning of the study (p = 0.017). ER22/23EK was found in 3% of the subjects and carriers had a lower prevalence of hypertension. Adrenal and gonadal steroids are associated to impairment of the ageing health condition in elderly individuals living independently in Spain. ER22/23EK polymorphism of the GC-R gene has a low prevalence in our population.     

Metabolic changes in the anterior and posterior cingulate cortices of the normal aging brain: proton magnetic resonance spectroscopy study at 3 T

Magnetic resonance spectroscopy (MRS) can explore aging at a molecular level. In this study, we investigated the relationships between regional concentrations of metabolites (such as choline, creatine, myo-inositol, and N-acetyl-aspartate) and normal aging in 30 cognitively normal subjects (15 women and 15 men, age range 22–82, mean = 49.9 ± 18.3 years) using quantitative proton magnetic resonance spectroscopy. All MR scans were performed using a 3 T scanner. Point resolved spectroscopy was used as the volume selection method for the region-of-interest and the excitation method for water suppression. Single voxel spectroscopy with short echo time of 39 ms and repetition time of 2,000 ms was employed. Single voxels were placed in the limbic regions, i.e., anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), and left and right hippocampi. Cerebrospinal fluid normalization and T1 and T2 correction factors were implemented in the calculation of absolute metabolite concentrations. A standardized T1W 3D volumetric fast field echo and axial T2-weighted fast spin-echo images were also acquired. Our results showed significant positive correlation of choline (r = 0.545, p = 0.002), creatine (r = 0.571, p = 0.001), and N-acetyl-aspartate (r = 0.674, p < 0.001) in the ACC; choline (r = 0.614, p < 0.001), creatine (r = 0.670, p < 0.001), and N-acetyl-aspartate (r = 0.528, p = 0.003) in the PCC; and NAA (r = 0.409, p = 0.025) in the left hippocampus, with age. No significant gender effect on metabolite concentrations was found. In aging, increases in choline and creatine might suggest glial proliferation, and an increase in N-acetyl-aspartate might indicate neuronal hypertrophy. Such findings highlight the metabolic changes of ACC and PCC with age, which could be compensatory to an increased energy demand coupled with a lower cerebral blood flow.     

Age and gender effects on submental motor-evoked potentials

It is not known whether there are age- and/or gender-related differences in magnitude of motor-evoked potentials (MEPs) of the submental muscles. Knowledge of this is important in investigations of neurophysiological aspects of swallowing. Forty healthy participants (20 males, 20 females; 20 young [21–35 years], 20 old [53–88 years]) were recruited. Surface electromyography (EMG) electrodes were placed at midline underlying the submental muscle group. Age- and gender-related differences were evaluated in two neurophysiologic measures of swallowing: MEPs stimulated by single-pulse transcranial magnetic stimulation (TMS) over the motor cortex and surface electromyography (sEMG) recorded from the same submental muscle group during non-stimulated swallows. The older participants had larger MEPs during saliva swallowing than the young participants (p = 0.04, d = 0.86). Conversely, the older participants had lower amplitude submental EMG activity during non-stimulated swallows (p = 0.045, d = 0.67). Gender had no significant effect on MEP magnitude and on submental activity during saliva swallowing. There were no effects of age or gender on MEP latencies. These findings suggest deterioration in muscle function with age in a sample of healthy adults presenting with functional swallowing. We speculate that muscular decline is partially ameliorated by increased cortical activity—i.e., increased submental MEPs—so as to preserve swallowing function in healthy older subjects. These findings emphasize the need for different reference points for evaluation of submental MEPs of different age groups.     

Association of healthy aging with parental longevity

Various measures incorporated in geriatric assessment have found their way into frailty indices (FIs), which have been used as indicators of survival/mortality and longevity. Our goal is to understand the genetic basis of healthy aging to enhance its evidence base and utility. We constructed a FI as a quantitative measure of healthy aging and examined its characteristics and potential for genetic analyses. Two groups were selected from two separate studies. One group (OLLP for offspring of long-lived parents) consisted of unrelated participants at least one of whose parents was age 90 or older, and the other group of unrelated participants (OSLP for offspring of short-lived parents), both of whose parents died before age 76. FI₃₄ scores were computed from 34 common health variables and compared between the two groups. The FI₃₄ was better correlated than chronological age with mortality. The mean FI₃₄ value of the OSLP was 31 % higher than that of the OLLP (P = 0.0034). The FI₃₄ increased exponentially, at an instantaneous rate that accelerated 2.0 % annually in the OLLP (P = 0.024) and 2.7 % in the OSLP (P < < 0.0001) consequently yielding a 63 % larger accumulation in the latter group (P = 0.0002). The results suggest that accumulation of health deficiencies over the life course is not the same in the two groups, likely due to inheritance related to parental longevity. Consistent with this, sib pairs were significantly correlated regarding FI₃₄ scores, and heritability of the FI₃₄ was estimated to be 0.39. Finally, hierarchical clustering suggests that the OLLP and OSLP differ in their aging patterns. Variation in the FI₃₄ is, in part, due to genetic variation; thus, the FI₃₄ can be a phenotypic measure suitable for genetic analyses of healthy aging.

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Low mitochondrial DNA content associates with familial longevity: the Leiden Longevity Study

Long-lived individuals delay aging and age-related diseases like diabetes, hypertension, and cardiovascular disease. The exact underlying mechanisms are largely unknown, but enhanced mitochondrial biogenesis and preservation of mitochondrial function have been suggested to explain healthy ageing. We investigated whether individuals belonging to long-lived families have altered mitochondrial DNA (mtDNA) content, as a biomarker of mitochondrial biogenesis and measured expression of genes regulating mitochondrial biogenesis. mtDNA and nuclear DNA (nDNA) levels were measured in blood samples from 2,734 participants from the Leiden Longevity Study: 704 nonagenarian siblings, 1,388 of their middle-aged offspring and 642 controls. We confirmed a negative correlation of mtDNA content in blood with age and a higher content in females. The middle-aged offspring had, on average, lower levels of mtDNA than controls and the nonagenarian siblings had an even lower mtDNA content (mtDNA/nDNA ratio = 0.744 ± 0.065, 0.767 ± 0.058 and 0.698 ± 0.074, respectively; p_{controls-offspring} = 3.4 × 10⁻¹², p_{controls-nonagenarians} = 6.5 × 10⁻⁶), which was independent of the confounding effects of age and gender. Subsequently, we examined in a subset of the study the expression in blood of two genes regulating mitochondrial biogenesis, YY1 and PGC-1α. We found a positive association of YY1 expression and mtDNA content in controls. The observed absence of such an association in the offspring suggests an altered regulation of mitochondrial biogenesis in the members of long-lived families. In conclusion, in this study, we show that mtDNA content decreases with age and that low mtDNA content is associated with familial longevity. Our data suggest that preservation of mitochondrial function rather than enhancing mitochondrial biogenesis is a characteristic of long-lived families.     

Exercise effects on bone mineral density in older adults: a meta-analysis of randomized controlled trials

The purpose of the study was to assess the effects of exercise interventions with different impact loading characteristics on lumbar spine (LS) and femoral neck (FN) bone mineral density (BMD) in older adults. We searched electronic databases and hand searched selected journals up to February 2011 for randomized controlled trials (RCTs) investigating the effects of impact exercise interventions on LS and FN BMD in older adults. Exercise protocols were categorized according to impact loading characteristics. Weighted mean difference (WMD) meta-analyses were undertaken. Heterogeneity amongst trials and publication bias was tested. Random-effects models were applied. Trial quality assessment was also undertaken. Nineteen RCTs, including 1577 subjects, met the inclusion criteria. Twenty-two study group comparisons reported BMD data at the LS. Meta-analysis showed a significant change in BMD at this site (WMD 0.011 g/cm², 95% CI 0.003 to 0.020; p = 0.007), although results were moderately inconsistent (I² = 52.2%). BMD data at the FN were available from 19 study group comparisons among older adults. Results were inconsistent (I² = 63.6%) in showing a significant positive effect of exercise on BMD at this site (WMD 0.016 g/cm², 95% CI 0.005 to 0.027; p = 0.004). Combined loading studies of impact activity mixed with high-magnitude joint reaction force loading through resistance training were effective at LS (WMD 0.016 g/cm², 95% CI 0.002 to 0.036; p = 0.028), and no inconsistency existed among these trials. Odd-impact protocols were also effective in increasing BMD at LS (WMD 0.039 g/cm², 95% CI 0.002 to 0.075; p = 0.038) and FN (WMD 0.036 g/cm², 95% CI 0.012 to 0.061; p = 0.004), although heterogeneity was evident (I² = 87.5% and I² = 83.5%, respectively). We found consistency among results for low-impact and resistance exercise studies on LS and FN, although non-significant BMD changes were evident amongst these types of protocols at any site and amongst the RCTs that provided a combined loading impact exercise at FN. Funnel plots showed no evidence of publication bias. Trial quality was moderate to high. The findings from our meta-analysis of RCTs support the efficacy of exercise for increasing LS and FN BMD in older adults.     

Evaluation of Four Risk-Scoring Methods to Predict Long-Term Outcomes in Patients Undergoing Aorto-Bifemoral Bypass for Aorto-Iliac Occlusive Disease

This study was done to determine the usefulness of the American Society of Anesthesiologists (ASA) classification, the comorbidity Charlson index unadjusted (CCIu),the comorbidity Charlson index adjusted by age (CCIa), and the Glasgow aneurysm score (GAS) for postoperative morbimortality and survival in patients treated with aorto-bifemoral bypass (AFB) for aorto-iliac occlusive disease (AIOD). A series of 278 patients who underwent AFB were restrospectively studied. For the CCIu, CCIa, ASA, and GAS, receiver operating characteristics curve analysis for prediction of morbidity showed area under the curves of 0.61 (p = 0.004), 0.59 (p = 0.026), 0.569 (p = 0.087), and 0.63 (p = 0.001), respectively. Additionally, univariate analysis showed that CCIa (p = 0.016) and GAS (p = 0.006) were associated significantly with an increased risk of developing complications. Furthermore, CCIa (p < 0.001) and GAS (p = 0.001) showed a significant association with survival. Finally, the variable age was related to morbidity (p = 0.004), mortality (p = 0.038), and survival (p < 0.001). The comorbididity and the age should be taken in account in clinical treatment decisions for patients with AIOD. The CCIa and GAS may play a role as predictive factors for postoperative morbidity and survival after AFB.     

Chronic training increases blood oxidative damage but promotes health in elderly men

The objective of the present study was to investigate a large panel of oxidative stress biomarkers in long-term trained elderly men to analyse the effects of chronic training on an aged population. We collected blood samples from two groups of male volunteers older than 65 years who maintain a measure of functional independence: one group of sedentary subjects without a history of regular physical activity and the other of subjects who have sustained training, starting during middle age (mean training time = 49 ± 8 years). We studied morbidity and polypharmacy, as well as haematological parameters including red cell count, haemoglobin concentration, haematocrit, mean corpuscular volume, red cell distribution width and several oxidative biomarkers including protein carbonyl content and lipid peroxidation in plasma and erythrocytes, red blood cell H₂O₂-induced haemolysis test, plasma total antioxidant activity and the main antioxidant enzymes of erythrocytes: superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase. After adjusting for confounding factors, we observed an increase in all oxidative damage biomarkers in the plasma and erythrocytes of the long-term exercise group. However, we reported a decrease in the number of diseases per subject with statistical differences nearly significant (p = 0.061), reduced intake of medications per subject and lower levels of red cell distribution width in the chronic exercise group. These results indicate that chronic exercise from middle age to old age increases oxidative damage; however, chronic exercise appears to be an effective strategy to attenuate the age-related decline in the elderly.     

Contributions of mild parkinsonian signs to gait performance in the elderly

Mild parkinsonian signs (MPS) and gait abnormalities are common in aging, but the association between MPS and objective gait measures is not established in the elderly. This study aims to identify the link between MPS and quantitative gait measures, as well as to determine the pathogenesis of MPS in non-demented community-dwelling older adults without idiopathic Parkinson’s disease or other parkinsonian syndromes. Three hundred seventy-four non-demented older adults (mean age, 76.44 ± 6.71 years, 57 % women) participated in this study, where comprehensive neurological and medical assessments were conducted. We defined MPS based on the presence of any one of bradykinesia, rigidity, or rest tremor. Velocity and spatial, temporal, and variability gait parameters were recorded using an instrumented walkway. The associations of MPS and gait parameters as well as the relationship of individual MPS with medical illnesses were assessed with linear regressions controlling for key covariates. Participants with MPS walked slower and with disturbed spatial and variability components of gait compared to those without MPS. Bradykinesia was associated with worse spatial and variability gait parameters. This association was only significant for axial bradykinesia, but not for the presence of bradykinesia in the limbs. Cerebrovascular disease (β = .20, p < .01) was associated with bradykinesia, whereas cardiovascular disease (β = .15, p < .05) was associated with rigidity. Among MPS, bradykinesia but not rigidity or tremor was associated with worse quantitative gait performance in older adults. Cerebrovascular disease, a preventable condition, was specifically associated with bradykinesia.     

Association between subjective well-being and exceptional longevity in a longevity town in China: a population-based study

To examine the associations of cognitive and emotional facets (measured by life satisfaction [LS], positive affect [PA], negative affect [NA], and affect balance [AB]) of subjective well-being (SWB) with exceptional longevity (EL), we conducted a population-based study with 463 EL individuals (95+, EL group) recruited from a longevity town of Rugao, China (N = 755, with a response rate of 71.6 %), and 926 elderly individuals (60–69, elderly/control group). The population-based controls were sampled from the resident registry according to the gender ratio of the EL group. We found that the EL group had significantly higher levels of LS (30.74 vs. 28.93), PA (3.91 vs. 3.67), and AB (7.89 vs. 7.40) and a lower level of NA (1.02 vs. 1.27) than the elderly group. Multivariate logistic regression analysis revealed that higher levels of LS, PA, AB, and NA were significantly associated with EL, with odds ratios (ORs) of 1.98 (95 % CI, 1.36–2.89), 2.35 (95 % CI, 1.59–3.48), 2.56 (95 % CI, 1.75–3.75), and 0.50 (95 % CI, 0.33–0.74), respectively. Stratification analysis showed that the associations were significant in the healthy subsample, with the following ORs: LS = 2.31, PA = 2.53, AB = 3.05, and NA = 0.39. In conclusion, SWB, with high cognitive and emotional facets, was associated with EL in the healthy Rugao population. The findings imply that interventions that aim to improve elderly individuals’ SWB may promote their quality of life and, ultimately, EL.     

MAP3K7 and GSTZ1 are associated with human longevity: a two-stage case–control study using a multilocus genotyping

The pathways that regulate energy homeostasis, the mechanisms of damage repair, and the signaling response to internal environmental changes or external signals have been shown to be critical in modulating lifespan of model organisms and humans. In order to investigate whether genetic variation of genes involved in these pathways contribute to longevity, a two-stage case–control study in two independent sets of long-lived individuals from Calabria (Italy) was performed. In stage 1, 317 SNPs in 104 genes were analyzed in 78 cases (median age 98 years) and 71 controls (median age 67 years). In stage 2, 31 candidate SNPs identified in stage 1 (π_markers = 0.1) were analyzed in an independent sample composed by 288 cases (median age 92 years) and 554 controls (median age 67 years). Two SNPs, rs282070 located in intron 1 of the MAP3K7 gene, and rs2111699 located in intron 1 of the GSTZ1 gene, were significantly associated (after adjustment for multiple testing) with longevity in stage 2 (p = 1.1 × 10⁻³ and p = 1.4 × 10⁻³, respectively). Interestingly, both genes are implicated in the cellular response to internal and external environmental changes, playing a crucial role in the inflammation processes that accompany aging. Our data confirm that long-lived subjects are endowed with genetic variants that allow them to optimize these cellular responses and to better deal with environmental and internal stresses.

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Disease Knowledge and General Self-Efficacy Among Adolescents with Thalassemia Major and Their Parents’ Perspective

Thalassemia major can affect physical, psycho-social and economic life of patients and their parents. The aim of the study was to assess the disease knowledge and general self-efficacy among adolescents with Thalassemia major and their parents’ perspective with a view to develop an informational booklet on thalassemia. In a cross-sectional study 50 adolescents along with 48 parents were recruited from the hematology day care centre of a tertiary care facility. Ethical clearance from institute ethics committee, written informed consent from parent and assent from the adolescent were taken. Consecutive participants those who consented were enrolled in the study. Adolescents between the age group of 10–18 years, and their parents completed the self-developed subject data sheet, knowledge questionnaire and standardized general self-efficacy tools. The mean knowledge scores of the adolescent and their parents related to thalassemia were 13.9 ± 2.9 and 13.7 ± 3.6 respectively, while the perceived GSE scores of the adolescent along with the parents’ perspective were 30.1 ± 6.1 and 29.3 ± 6.5. Positive correlation between the adolescents’ knowledge with GSE (r = 0.464, p = 0.007) was observed. The knowledge of the adolescents and their parents showed significant association with the education (p = 0.001, p = 0.002) residence (p = 0.04 and p = 0.01) and parents’ employment (p = 0.04). The knowledge of adolescents with thalassemia and their parents is limited. There is need to counsel the adolescents and their parents about the disease and its management in order to improve the GSE of these adolescents.     

Low computed tomography coronary artery calcium scores in familial longevity: the Leiden Longevity Study

Offspring of long-lived parents have a low prevalence of cardiovascular disease in middle age. The purposes of this study were to investigate calcium scores in offspring as compared to controls and to determine the influence of cardiovascular risk factors. CT coronary artery calcium score was measured in offspring of long-lived families (n = 244, 125 males) and their partners (n = 223, 96 males) who served as controls. Calcium scores were analyzed separately for sexes. Subjects were grouped by very low calcium score ≤10 and scores above 10. Nonparametric Mann-Whitney test, chi-squared tests, and logistic regression analyses were performed to determine the association between calcium scores, familial longevity, and cardiovascular risk factors. More offspring of long-lived parents had lower calcium scores than controls. In men, 34 % of offspring had score ≤10 versus 21 % of controls (odds ratio (OR) and 95 % confidence interval (CI) 2.0, 1.08–3.7, p = 0.028). In women, 70 % of offspring had score ≤10 versus 54 % of controls (OR 1.9, 95 % CI 1.13–3.4, p = 0.019). Differences remained significant after correction for age (men, p = 0.043 and women, p = 0.003) and further correction for major risk factors in women, indicating genetic influence for lower calcium scores. In men, the association was found to be influenced by cardiovascular risk factors. Men and women with a familial propensity to become long-lived have lower coronary artery calcium scores than controls. Low scores may indicate a younger biologic arterial age associated with a low risk for incident cardiovascular disease.     

Late-life alcohol consumption and cognitive function in elderly men

Moderate alcohol consumption (one to two drinks per day) has been associated with better cognitive function and lower risk of developing dementia in the elderly. In light of alcohol’s well-known neurotoxic properties, more evidence from well-controlled population-based studies is required. The objective of this study was to examine whether self-reported alcohol intake at age 70 is linked to cognitive function (assessed by trail making tests (TMTs) A and B, which are measures of attention, mental speed, and flexibility) in a population-based cohort consisting of 652 cognitively healthy elderly men. Linear regression models were used to assess both cross-sectional (i.e., age 70) and prospective (i.e., age 77) associations between alcohol intake and cognitive function. The analyses were adjusted for education, body mass index, energy intake, self-reported physical activity, smoking, a history of hypertension or diabetes, apolipoprotein E ε4 status, and cholesterol levels at the age of 70. Baseline data were obtained from 1990 to 1996. Self-reported alcohol intake (mean 6.9 ± 7.1 g/day) was associated with better performance on TMT-B at ages 70 and 77 (β = −0.87, p < 0.001). In contrast, alcohol intake was not predictive of the difference in performance on these tests between ages 70 and 77. Despite cross-sectional associations with performance in a test of executive functioning, moderate intake of alcohol was not linked to differences in cognitive performance between ages 70 and 77 in the present study. Thus, our findings do not support the view that daily moderate alcohol consumption is a recommendable strategy to slow cognitive aging in elderly populations.     

Apolipoprotein E-related all-cause mortality in hospitalized elderly patients

The most common apolipoprotein E (APOE) allelic variation is implicated in many age-related diseases and human longevity with controversial findings. We investigated the effect of APOE gene polymorphism on all-cause mortality in elderly patients taking into consideration the functional disability, cognitive impairment, malnutrition, and the occurrence of common age-related diseases. APOE genotypes were determined in 2,124 geriatric hospitalized patients (46.5% men and 53.5% women; mean age, 78.2 ± 7.1 years; range, 65–100 years). At hospital admission, all patients underwent a comprehensive geriatric assessment to evaluate functional disability, cognitive status, nutritional status, and comorbidity. The main and secondary diagnoses at hospital discharge were also recorded. Mortality status was evaluated in all patients after a maximum follow-up of 5 years (range, from 1.26 to 5.23 years; median, 2.86 years). During the study period, 671 patients died (32.0%). At hospital admission, these patients showed a significant higher prevalence of cardiovascular diseases (56.3% vs 53.4%; p = 0.007), neoplasias (32.3% vs 13.7%; p < 0.001), and lower prevalence of neurodegenerative diseases (17.7% vs 20.7%; p < 0.001) than survived patients. Moreover, they also showed an higher prevalence of disability (52.0% vs 25.6%; p < 0.001), cognitive impairment (31.0% vs 18.8%; p < 0.001), and malnutrition (74.0% vs 46.1%; p < 0.001) than survived patients. In the overall study population, the APOE ε2 allele was significantly associated to neurodegenerative diseases (odds ratio = 0.59; 95% confidence interval (CI), 0.37–0.94). No significant association between the APOE polymorphism and disability, malnutrition, co-morbidity status, and with all-cause mortality was observed. In patients with cardiovascular diseases, however, a decreased risk of all-cause mortality was found in the ε2 allele carriers (hazard ratio = 0.56; 95% CI, 0.36–0.88). In this population, APOE allele variants might play a role on cardiovascular disease-related mortality.