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This study measured the subclinical frailty of centenarians by looking at the accumulation of their biological abnormalities. For this aim, a biological Frailty Index (FI) was computed in centenarians living in Northern Italy. The median value of the biological FI was 0.33 (interquartile range, IQR 0.28–0.41). The biological FI did not significantly differ between women (0.34, IQR 0.31–0.39) and men (0.32, IQR 0.26–0.43). The biological FI seems to have a narrower distribution compared to clinical FI we previously computed in the same cohort. In conclusion, our study suggests that centenarians benefit from exceptional biological reserves that might be underestimated by clinical appearances. [ABSTRACT FROM AUTHOR]

Background: Vitamin E represents a potent antioxidant and anti-inflammatory system, playing a role in Alzheimer's disease (AD). Different plasma concentrations of the forms of vitamin E are observed in AD compared to cognitively healthy subjects. Aim: Since these modifications may modulate the markers of oxidative stress and cellular aging, we aim to explore the relationship between vitamin E forms and leukocyte telomere length (LTL) in AD. Methods: 53 AD subjects and 40 cognitively healthy controls (CTs) were enrolled. The vitamin E forms (α-, β-, γ- and δ-tocopherol, α-, β-, γ- and δ-tocotrienol), the ratio of α-tocopherylquinone/α-tocopherol and 5-nitro-γ-tocopherol/γ-tocopherol (markers of oxidative/nitrosative damage) and LTL were measured. Results and discussion: Regression model was used to explore the associations of vitamin E forms and LTL with AD. The interaction of LTL in the association between vitamin E forms and AD was tested. AD subjects showed significantly lower concentrations of α-, β-, γ- and δ-tocopherol, α- and δ-tocotrienol, total tocopherols, total tocotrienols and total vitamin E compared to CTs. AD subjects showed higher values of nitrosative/oxidative damage. The adjusted analyses confirmed a significant relationship of AD with plasma concentrations of α- and β-tocopherols, δ-tocotrienol, total tocopherols, total tocotrienol, total vitamin E and oxidative/nitrosative damage. However, nitrosative damage was significantly associated with AD only in subjects with higher LTL and not in those expressing marked cellular aging. Conclusions: Our study confirms the role of vitamin E in AD pathology and indicates that nitrosative damage influences the association with AD only in subjects characterized by longer LTL. [ABSTRACT FROM AUTHOR]

Frailty has been indicated as a way for capturing biological aging of the individual and Frailty Index (FI) may serve for this purpose. This study designed the FI in a cohort of centenarians, their offspring and control subjects sex- and age-matched with offspring. The FI mean value was 0.47 (SD 0.13) in centenarians, 0.15 (SD 0.12) in their offspring, and 0.22 (SD 0.14) in controls (p < 0.001). The difference between offspring and controls was statistically significant (p = 0.003). The correlation between FI and age was significant in offspring (r = 0.46, p < 0.001), close to significance in controls (r = 0.25, p = 0.08) and not significant in centenarians. Our study confirms that FI is a marker of biological age useful to discriminate different degrees of frailty even at extremely advanced age. [ABSTRACT FROM AUTHOR]

We describe a family composed of six siblings, four of which affected by late-onset Alzheimer's disease (LOAD). We constructed the family pedigree, evaluated mutations usually associated with early-onset Alzheimer's disease (APP, PSEN1, PSEN2), and assessed polymorphisms in the apolipoprotein E (APOE) gene and in cytokine genes that we had previously found to be associated with a higher risk of LOAD (IL-10, IL-6, TNF-α). Results showed that all subjects carried one ε4 allele of the APOE gene and those with the earliest age of onset exhibited the AA (-1082) IL-10 and the CC (-174) IL-6 genotypes. The only male had a genetic profile which also included the A (-308) TNF-α allele. These data confirm the role of the APOE gene as genetic risk factor in LOAD, and suggest that the risk of developing AD may be governed by a 'susceptibility profile' involving polymorphisms in inflammatory genes. [ABSTRACT FROM AUTHOR]

Background and aims: Several indices of subclinical atherosclerosis (ATS), including ultrasound US) scan of carotid vessels, have received attention in clinical studies of the general population. Since inflammation takes part in the development of ATS, we studied the relationship between US imaging of carotid vessels and genetic predisposition to inflammation, in both elderly subjects without acknowledged CV risk factors and elderly subjects with acknowledged CV risk factors undergoing primary prevention. Methods: Seventy-two elderly subjects (aged between 65-84) were divided into three groups on the basis of cardiovascular (CV) risk G0: 0-9%, G1: 10-20% and G2: >20%) according to the NCEP Adult Panel III Report. They underwent US evaluation of carotid arteries and were analyzed for single nucleotide polymorphisms in the genes of a number of cytokines: TNF-α TGF-β1, IL-10, IL-6 and IFN-γ. Results: Asymptomatic carotid plaque (ACP) was detected in 19 subjects, not only in those belonging to the major risk group (36.8%) but also in those at lower risk (63.2%). In these subjects, we found a different genotype distribution in the polymorphisms of IFN-γ (+874), IL-6 (-174) and IL-10 (-1082). The TT +874 IFN-γ and GG -174 IL-6 high producer-genotypes and the AA IL-10 low producer-genotype were indeed more frequent in the ACP group IFN-γ p=0.000 and IL-6: p=0.004). We found no correlation between genotype and carotid intima-media thickening. Conclusions: Our data suggest that, in the elderly, inflammation-associated polymorphisms are related to atherogenesis and that the finding of ACP on US scan can be valuable in identifying subjects at risk for CV events, even if they lack traditional cardiovascular risk factors such as an increase in IMT. [ABSTRACT FROM AUTHOR]

Background and aims: Peptydil prolyl cis-trans isomerase (PIN-1), which specifically regulates the conformational changes following phosphorylation of several proteins, targets the inactive hyperphosphorylated tau on the Thr231-Pro motif and directly restores its biological function. Interestingly, PIN-1 is oxidatively inhibited not only in Alzheimer's disease brain but also in the hippocampi of mild cognitive impairment (MCI) subjects. The PIN-1 gene is characterized by two single nucleotide polymorphisms (SNPs) in the promoter region which are associated with the risk of Alzheimer's disease. The aim of this study was to analyse the genotype and allele distributions of these PIN-1 SNPs in MCI subjects diagnosed respectively as amnestic MCI (a-MCI) and multiple impaired cognitive domains (mcd-MCI) on the basis of cognitive features. Methods: -667 T/C and -842 C/G SNPs were genotyped by polymerase chain reaction (PCR) amplification and direct sequencing in 43 MCI subjects, with the intention of comparing -667 and -842 SNP frequencies with those previously described in 111 Alzheimer's disease patients (AD) and 73 healthy controls (HC). Results: The allele frequencies of the -842 C/G SNP in a-MCI subjects are similar to those of AD subjects, while those of mcd-MCI are comparable to HC (G allele 83% in both a-MCI and AD; 95% and 94% in mcd-MCI and HC, respectively). A similar trend is also observed in -842 C/G genotypes. Conclusions: Since a-MCI is thought to be the preclinical form of AD, the similar genotype distribution of -842 SNP in AD and a-MCI, but not in mcd-MCI, suggests that it is potentially involved in the conversion of a-MCI to AD. In conclusion, these findings support the theory that polymorphisms of the PIN-1 gene can affect neurodegeneration and its clinical progression. [ABSTRACT FROM AUTHOR]